TY  - JOUR
AU  - Živančević, Katarina
AU  - Baralić, Katarina
AU  - Vukelić, Dragana
AU  - Marić, Đurđica
AU  - Kotur-Stevuljević, Jelena
AU  - Ivanišević, Jasmina
AU  - Savić, Miroslav
AU  - Batinić, Bojan
AU  - Janković, Radmila
AU  - Buha-Đorđević, Aleksandra
AU  - Antonijević-Miljaković, Evica
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5614
AB  - Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.
PB  - Elsevier Inc.
T2  - Environmental Research
T1  - Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach
VL  - 252
IS  - 1
SP  - 118680
DO  - 10.1016/j.envres.2024.118680
ER  - 

@article{
author = "Živančević, Katarina and Baralić, Katarina and Vukelić, Dragana and Marić, Đurđica and Kotur-Stevuljević, Jelena and Ivanišević, Jasmina and Savić, Miroslav and Batinić, Bojan and Janković, Radmila and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2024",
abstract = "Metals exert detrimental effects on various systems within the body, including the nervous system. Nevertheless, the dose-response relationship concerning the administration of low doses of metal mixtures remains inadequately explored. The assessment of neurotoxic effects of lead, cadmium, mercury, and arsenic mixture (MIX) administered at low dose ranges, was conducted using an in vivo approach. A subacute study was conducted on a rat model consisting of a control and five treatment groups subjected to oral exposure with gradually increasing doses (from MIX 1 to MIX 5). The results indicated that behavioural patterns in an already developed nervous system displayed a reduced susceptibility to the metal mixture exposure with tendency of higher doses to alter short term memory. However, the vulnerability of the mature brain to even minimal amounts of the investigated metal mixture was evident, particularly in the context of oxidative stress. Moreover, the study highlights superoxide dismutase's sensitivity as an early-stage neurotoxicity marker, as indicated by dose-dependent induction of oxidative stress in the brain revealed through Benchmark analysis. The narrowest Benchmark Dose Interval (BMDI) for superoxide dismutase (SOD) activity (1e-06 - 3.18e-05 mg As/kg b.w./day) indicates that arsenic may dictate the alterations in SOD activity when co-exposed with the other examined metals. The predicted Benchmark doses for oxidative stress parameters were very low, supporting “no-threshold” concept. Histopathological alterations were most severe in the groups treated with higher doses of metal mixture. Similarly, the brain acetylcholinesterase (AChE) activity demonstrated a dose-dependent decrease significant in higher doses, while BMDI suggested Cd as the main contributor in the examined metal mixture. These findings imply varying susceptibility of neurotoxic endpoints to different doses of environmentally relevant metal mixtures, advocating for risk assessment and regulatory measures to address metal pollution and enhance remediation strategies.",
publisher = "Elsevier Inc.",
journal = "Environmental Research",
title = "Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach",
volume = "252",
number = "1",
pages = "118680",
doi = "10.1016/j.envres.2024.118680"
}

Živančević, K., Baralić, K., Vukelić, D., Marić, Đ., Kotur-Stevuljević, J., Ivanišević, J., Savić, M., Batinić, B., Janković, R., Buha-Đorđević, A., Antonijević-Miljaković, E., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2024). Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach. in Environmental Research
Elsevier Inc.., 252(1), 118680.
https://doi.org/10.1016/j.envres.2024.118680

Živančević K, Baralić K, Vukelić D, Marić Đ, Kotur-Stevuljević J, Ivanišević J, Savić M, Batinić B, Janković R, Buha-Đorđević A, Antonijević-Miljaković E, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach. in Environmental Research. 2024;252(1):118680.
doi:10.1016/j.envres.2024.118680 .

Živančević, Katarina, Baralić, Katarina, Vukelić, Dragana, Marić, Đurđica, Kotur-Stevuljević, Jelena, Ivanišević, Jasmina, Savić, Miroslav, Batinić, Bojan, Janković, Radmila, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Neurotoxic effects of low dose ranges of environmental metal mixture in a rat model: The benchmark approach" in Environmental Research, 252, no. 1 (2024):118680,
https://doi.org/10.1016/j.envres.2024.118680 . .

TY  - JOUR
AU  - Pépin, Marion
AU  - Klimkowicz-Mrowiec, Aleksandra
AU  - Godefroy, Olivier
AU  - Delgado, P.
AU  - Carriazo, S.
AU  - Ferreira, A.C.
AU  - Golenia, A.
AU  - Malyszko, J.
AU  - Grodzicki, T.
AU  - Giannakou, K.
AU  - Paolisso, G.
AU  - Barbieri, M.
AU  - Garneata, L.
AU  - Mocanu, C.A.
AU  - Liabeuf, S.
AU  - Spasovski, G.
AU  - Zoccali, C.
AU  - Bruchfeld, A.
AU  - Farinha, A.
AU  - Arici, M.
AU  - Capasso, G.
AU  - Wiecek, A.
AU  - Massy, Z.A.
AU  - Andrade, A.
AU  - Bachmann, M.
AU  - Bumblyte, I.
AU  - Covic, A.C.
AU  - Endlich, N.
AU  - Engvig, A.
AU  - Fouque, D.
AU  - Franssen, C.
AU  - Frische, S.
AU  - Gesualdo, L.
AU  - Goumenos, D.
AU  - Mani, L.-Y.
AU  - Marti, H.-P.
AU  - Mayer, C.
AU  - Nielsen, R.
AU  - Pešić, Vesna
AU  - Rroji, M.
AU  - Sakkas, G.
AU  - Stevens, K.
AU  - Vazelov, E.
AU  - Viggiano, D.
AU  - Zacharia, L.
AU  - Hoorn, E.
AU  - Figurek, A.
AU  - Unwin, R.
AU  - Wagner, C.A.
AU  - Wanner, C.
AU  - Nitsch, D.
AU  - Fridolin, I.
AU  - Hafez, G.
AU  - Soler Romeo, M.J.
AU  - Batinić, Bojan
AU  - Carrasco, L.
AU  - Gansevoort, R.
AU  - Martino, G.
AU  - Mattace Raso, F.
AU  - Nistor, I.
AU  - Ortiz, A.
AU  - Rastenytė, D.
AU  - Stefan, G.
AU  - Tedeschi, G.
AU  - Bikbov, B.
AU  - Endlich, K.H.
AU  - Kurganaite, J.
AU  - Perico, N.
AU  - Remuzzi, G.
AU  - Trepiccione, F.
AU  - Blankestijn, P.
AU  - Eckardt, K.-U.
AU  - Fliser, D.
AU  - Gutiérrez-Jiménez, E.
AU  - Konig, M.
AU  - Rychlik, I.
AU  - Deleidi, M.
AU  - Reusz, G.
AU  - Farisco, M.
AU  - Imenez Silva, P.H.
AU  - Bobot, M.
AU  - Capolongo, G.
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5594
AB  - Background: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. Methods: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives. Results: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. Conclusions: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD.
PB  - John Wiley and Sons Inc
T2  - European Journal of Neurology
T1  - Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment
VL  - 30
IS  - 9
SP  - 2899
EP  - 2911
DO  - 10.1111/ene.15928
ER  - 

@article{
author = "Pépin, Marion and Klimkowicz-Mrowiec, Aleksandra and Godefroy, Olivier and Delgado, P. and Carriazo, S. and Ferreira, A.C. and Golenia, A. and Malyszko, J. and Grodzicki, T. and Giannakou, K. and Paolisso, G. and Barbieri, M. and Garneata, L. and Mocanu, C.A. and Liabeuf, S. and Spasovski, G. and Zoccali, C. and Bruchfeld, A. and Farinha, A. and Arici, M. and Capasso, G. and Wiecek, A. and Massy, Z.A. and Andrade, A. and Bachmann, M. and Bumblyte, I. and Covic, A.C. and Endlich, N. and Engvig, A. and Fouque, D. and Franssen, C. and Frische, S. and Gesualdo, L. and Goumenos, D. and Mani, L.-Y. and Marti, H.-P. and Mayer, C. and Nielsen, R. and Pešić, Vesna and Rroji, M. and Sakkas, G. and Stevens, K. and Vazelov, E. and Viggiano, D. and Zacharia, L. and Hoorn, E. and Figurek, A. and Unwin, R. and Wagner, C.A. and Wanner, C. and Nitsch, D. and Fridolin, I. and Hafez, G. and Soler Romeo, M.J. and Batinić, Bojan and Carrasco, L. and Gansevoort, R. and Martino, G. and Mattace Raso, F. and Nistor, I. and Ortiz, A. and Rastenytė, D. and Stefan, G. and Tedeschi, G. and Bikbov, B. and Endlich, K.H. and Kurganaite, J. and Perico, N. and Remuzzi, G. and Trepiccione, F. and Blankestijn, P. and Eckardt, K.-U. and Fliser, D. and Gutiérrez-Jiménez, E. and Konig, M. and Rychlik, I. and Deleidi, M. and Reusz, G. and Farisco, M. and Imenez Silva, P.H. and Bobot, M. and Capolongo, G.",
year = "2023",
abstract = "Background: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. Methods: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives. Results: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. Conclusions: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD.",
publisher = "John Wiley and Sons Inc",
journal = "European Journal of Neurology",
title = "Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment",
volume = "30",
number = "9",
pages = "2899-2911",
doi = "10.1111/ene.15928"
}

Pépin, M., Klimkowicz-Mrowiec, A., Godefroy, O., Delgado, P., Carriazo, S., Ferreira, A.C., Golenia, A., Malyszko, J., Grodzicki, T., Giannakou, K., Paolisso, G., Barbieri, M., Garneata, L., Mocanu, C.A., Liabeuf, S., Spasovski, G., Zoccali, C., Bruchfeld, A., Farinha, A., Arici, M., Capasso, G., Wiecek, A., Massy, Z.A., Andrade, A., Bachmann, M., Bumblyte, I., Covic, A.C., Endlich, N., Engvig, A., Fouque, D., Franssen, C., Frische, S., Gesualdo, L., Goumenos, D., Mani, L.-Y., Marti, H.-P., Mayer, C., Nielsen, R., Pešić, V., Rroji, M., Sakkas, G., Stevens, K., Vazelov, E., Viggiano, D., Zacharia, L., Hoorn, E., Figurek, A., Unwin, R., Wagner, C.A., Wanner, C., Nitsch, D., Fridolin, I., Hafez, G., Soler Romeo, M.J., Batinić, B., Carrasco, L., Gansevoort, R., Martino, G., Mattace Raso, F., Nistor, I., Ortiz, A., Rastenytė, D., Stefan, G., Tedeschi, G., Bikbov, B., Endlich, K.H., Kurganaite, J., Perico, N., Remuzzi, G., Trepiccione, F., Blankestijn, P., Eckardt, K.-U., Fliser, D., Gutiérrez-Jiménez, E., Konig, M., Rychlik, I., Deleidi, M., Reusz, G., Farisco, M., Imenez Silva, P.H., Bobot, M.,& Capolongo, G.. (2023). Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment. in European Journal of Neurology
John Wiley and Sons Inc., 30(9), 2899-2911.
https://doi.org/10.1111/ene.15928

Pépin M, Klimkowicz-Mrowiec A, Godefroy O, Delgado P, Carriazo S, Ferreira A, Golenia A, Malyszko J, Grodzicki T, Giannakou K, Paolisso G, Barbieri M, Garneata L, Mocanu C, Liabeuf S, Spasovski G, Zoccali C, Bruchfeld A, Farinha A, Arici M, Capasso G, Wiecek A, Massy Z, Andrade A, Bachmann M, Bumblyte I, Covic A, Endlich N, Engvig A, Fouque D, Franssen C, Frische S, Gesualdo L, Goumenos D, Mani L, Marti H, Mayer C, Nielsen R, Pešić V, Rroji M, Sakkas G, Stevens K, Vazelov E, Viggiano D, Zacharia L, Hoorn E, Figurek A, Unwin R, Wagner C, Wanner C, Nitsch D, Fridolin I, Hafez G, Soler Romeo M, Batinić B, Carrasco L, Gansevoort R, Martino G, Mattace Raso F, Nistor I, Ortiz A, Rastenytė D, Stefan G, Tedeschi G, Bikbov B, Endlich K, Kurganaite J, Perico N, Remuzzi G, Trepiccione F, Blankestijn P, Eckardt K, Fliser D, Gutiérrez-Jiménez E, Konig M, Rychlik I, Deleidi M, Reusz G, Farisco M, Imenez Silva P, Bobot M, Capolongo G. Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment. in European Journal of Neurology. 2023;30(9):2899-2911.
doi:10.1111/ene.15928 .

Pépin, Marion, Klimkowicz-Mrowiec, Aleksandra, Godefroy, Olivier, Delgado, P., Carriazo, S., Ferreira, A.C., Golenia, A., Malyszko, J., Grodzicki, T., Giannakou, K., Paolisso, G., Barbieri, M., Garneata, L., Mocanu, C.A., Liabeuf, S., Spasovski, G., Zoccali, C., Bruchfeld, A., Farinha, A., Arici, M., Capasso, G., Wiecek, A., Massy, Z.A., Andrade, A., Bachmann, M., Bumblyte, I., Covic, A.C., Endlich, N., Engvig, A., Fouque, D., Franssen, C., Frische, S., Gesualdo, L., Goumenos, D., Mani, L.-Y., Marti, H.-P., Mayer, C., Nielsen, R., Pešić, Vesna, Rroji, M., Sakkas, G., Stevens, K., Vazelov, E., Viggiano, D., Zacharia, L., Hoorn, E., Figurek, A., Unwin, R., Wagner, C.A., Wanner, C., Nitsch, D., Fridolin, I., Hafez, G., Soler Romeo, M.J., Batinić, Bojan, Carrasco, L., Gansevoort, R., Martino, G., Mattace Raso, F., Nistor, I., Ortiz, A., Rastenytė, D., Stefan, G., Tedeschi, G., Bikbov, B., Endlich, K.H., Kurganaite, J., Perico, N., Remuzzi, G., Trepiccione, F., Blankestijn, P., Eckardt, K.-U., Fliser, D., Gutiérrez-Jiménez, E., Konig, M., Rychlik, I., Deleidi, M., Reusz, G., Farisco, M., Imenez Silva, P.H., Bobot, M., Capolongo, G., "Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment" in European Journal of Neurology, 30, no. 9 (2023):2899-2911,
https://doi.org/10.1111/ene.15928 . .

TY  - JOUR
AU  - Farisco, Michele
AU  - Zecchino, I.
AU  - Capasso, G.
AU  - Andrade, A.
AU  - Bachmann, M.
AU  - Bumblyte, I.
AU  - Covic, A.C.
AU  - Delgado, P.
AU  - Endlich, N.
AU  - Engvig, A.
AU  - Fouque, D.
AU  - Franssen, C.
AU  - Frische, S.
AU  - Garneata, L.
AU  - Gesualdo, L.
AU  - Giannakou, K.
AU  - Goumenos, D.
AU  - Kartal, A.T.
AU  - Mani, L.-Y.
AU  - Marti, H.-P.
AU  - Mayer, C.
AU  - Nielsen, R.
AU  - Pešić, Vesna
AU  - Rroji, M.
AU  - Sakkas, G.
AU  - Spasovski, G.
AU  - Stevens, K.I.
AU  - Vazelov, E.
AU  - Viggiano, D.
AU  - Zacharia, L.
AU  - Ferreira, A.C.
AU  - Malyszko, J.
AU  - Hoorn, E.
AU  - Figurek, A.
AU  - Unwin, R.
AU  - Wagner, C.
AU  - Wanner, C.
AU  - Bruchfeld, A.
AU  - Pepin, M.
AU  - Wieçek, A.
AU  - Nitsch, D.
AU  - Fridolin, I.
AU  - Hafez, G.
AU  - Soler, M.J.
AU  - Barbieri, M.
AU  - Batinić, Bojan
AU  - Carrasco, L.
AU  - Carriazo, S.
AU  - Gansevoort, R.
AU  - Martino, G.
AU  - Raso, F.M.
AU  - Nistor, I.
AU  - Ortiz, A.
AU  - Paolisso, G.
AU  - Rastenytė, D.
AU  - Stefan, G.
AU  - Tedeschi, G.
AU  - Massy, Z.A.
AU  - Bikbov, B.
AU  - Endlich, K.H.
AU  - Godefroy, O.
AU  - Chillon, J.-M.
AU  - Kossioni, A.
AU  - Kurganaite, J.
AU  - Perico, N.
AU  - Remuzzi, G.
AU  - Grodzicki, T.
AU  - Trepiccione, F.
AU  - Zoccali, C.
AU  - Arici, M.
AU  - Blankestijn, P.
AU  - Eckardt, K.-U.
AU  - Fliser, D.
AU  - Jiménez, E.
AU  - König, M.
AU  - Rychlik, I.
AU  - Deleidi, M.
AU  - Reusz, G.
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5595
PB  - Oxford University Press
T2  - Nephrology Dialysis Transplantation
T1  - The need for a multi-disciplinary reflection about frailty and cognitive impairment in chronic kidney disease
VL  - 38
IS  - 5
SP  - 1064
EP  - 1066
DO  - 10.1093/ndt/gfac334
ER  - 

@article{
author = "Farisco, Michele and Zecchino, I. and Capasso, G. and Andrade, A. and Bachmann, M. and Bumblyte, I. and Covic, A.C. and Delgado, P. and Endlich, N. and Engvig, A. and Fouque, D. and Franssen, C. and Frische, S. and Garneata, L. and Gesualdo, L. and Giannakou, K. and Goumenos, D. and Kartal, A.T. and Mani, L.-Y. and Marti, H.-P. and Mayer, C. and Nielsen, R. and Pešić, Vesna and Rroji, M. and Sakkas, G. and Spasovski, G. and Stevens, K.I. and Vazelov, E. and Viggiano, D. and Zacharia, L. and Ferreira, A.C. and Malyszko, J. and Hoorn, E. and Figurek, A. and Unwin, R. and Wagner, C. and Wanner, C. and Bruchfeld, A. and Pepin, M. and Wieçek, A. and Nitsch, D. and Fridolin, I. and Hafez, G. and Soler, M.J. and Barbieri, M. and Batinić, Bojan and Carrasco, L. and Carriazo, S. and Gansevoort, R. and Martino, G. and Raso, F.M. and Nistor, I. and Ortiz, A. and Paolisso, G. and Rastenytė, D. and Stefan, G. and Tedeschi, G. and Massy, Z.A. and Bikbov, B. and Endlich, K.H. and Godefroy, O. and Chillon, J.-M. and Kossioni, A. and Kurganaite, J. and Perico, N. and Remuzzi, G. and Grodzicki, T. and Trepiccione, F. and Zoccali, C. and Arici, M. and Blankestijn, P. and Eckardt, K.-U. and Fliser, D. and Jiménez, E. and König, M. and Rychlik, I. and Deleidi, M. and Reusz, G.",
year = "2023",
publisher = "Oxford University Press",
journal = "Nephrology Dialysis Transplantation",
title = "The need for a multi-disciplinary reflection about frailty and cognitive impairment in chronic kidney disease",
volume = "38",
number = "5",
pages = "1064-1066",
doi = "10.1093/ndt/gfac334"
}

Farisco, M., Zecchino, I., Capasso, G., Andrade, A., Bachmann, M., Bumblyte, I., Covic, A.C., Delgado, P., Endlich, N., Engvig, A., Fouque, D., Franssen, C., Frische, S., Garneata, L., Gesualdo, L., Giannakou, K., Goumenos, D., Kartal, A.T., Mani, L.-Y., Marti, H.-P., Mayer, C., Nielsen, R., Pešić, V., Rroji, M., Sakkas, G., Spasovski, G., Stevens, K.I., Vazelov, E., Viggiano, D., Zacharia, L., Ferreira, A.C., Malyszko, J., Hoorn, E., Figurek, A., Unwin, R., Wagner, C., Wanner, C., Bruchfeld, A., Pepin, M., Wieçek, A., Nitsch, D., Fridolin, I., Hafez, G., Soler, M.J., Barbieri, M., Batinić, B., Carrasco, L., Carriazo, S., Gansevoort, R., Martino, G., Raso, F.M., Nistor, I., Ortiz, A., Paolisso, G., Rastenytė, D., Stefan, G., Tedeschi, G., Massy, Z.A., Bikbov, B., Endlich, K.H., Godefroy, O., Chillon, J.-M., Kossioni, A., Kurganaite, J., Perico, N., Remuzzi, G., Grodzicki, T., Trepiccione, F., Zoccali, C., Arici, M., Blankestijn, P., Eckardt, K.-U., Fliser, D., Jiménez, E., König, M., Rychlik, I., Deleidi, M.,& Reusz, G.. (2023). The need for a multi-disciplinary reflection about frailty and cognitive impairment in chronic kidney disease. in Nephrology Dialysis Transplantation
Oxford University Press., 38(5), 1064-1066.
https://doi.org/10.1093/ndt/gfac334

Farisco M, Zecchino I, Capasso G, Andrade A, Bachmann M, Bumblyte I, Covic A, Delgado P, Endlich N, Engvig A, Fouque D, Franssen C, Frische S, Garneata L, Gesualdo L, Giannakou K, Goumenos D, Kartal A, Mani L, Marti H, Mayer C, Nielsen R, Pešić V, Rroji M, Sakkas G, Spasovski G, Stevens K, Vazelov E, Viggiano D, Zacharia L, Ferreira A, Malyszko J, Hoorn E, Figurek A, Unwin R, Wagner C, Wanner C, Bruchfeld A, Pepin M, Wieçek A, Nitsch D, Fridolin I, Hafez G, Soler M, Barbieri M, Batinić B, Carrasco L, Carriazo S, Gansevoort R, Martino G, Raso F, Nistor I, Ortiz A, Paolisso G, Rastenytė D, Stefan G, Tedeschi G, Massy Z, Bikbov B, Endlich K, Godefroy O, Chillon J, Kossioni A, Kurganaite J, Perico N, Remuzzi G, Grodzicki T, Trepiccione F, Zoccali C, Arici M, Blankestijn P, Eckardt K, Fliser D, Jiménez E, König M, Rychlik I, Deleidi M, Reusz G. The need for a multi-disciplinary reflection about frailty and cognitive impairment in chronic kidney disease. in Nephrology Dialysis Transplantation. 2023;38(5):1064-1066.
doi:10.1093/ndt/gfac334 .

Farisco, Michele, Zecchino, I., Capasso, G., Andrade, A., Bachmann, M., Bumblyte, I., Covic, A.C., Delgado, P., Endlich, N., Engvig, A., Fouque, D., Franssen, C., Frische, S., Garneata, L., Gesualdo, L., Giannakou, K., Goumenos, D., Kartal, A.T., Mani, L.-Y., Marti, H.-P., Mayer, C., Nielsen, R., Pešić, Vesna, Rroji, M., Sakkas, G., Spasovski, G., Stevens, K.I., Vazelov, E., Viggiano, D., Zacharia, L., Ferreira, A.C., Malyszko, J., Hoorn, E., Figurek, A., Unwin, R., Wagner, C., Wanner, C., Bruchfeld, A., Pepin, M., Wieçek, A., Nitsch, D., Fridolin, I., Hafez, G., Soler, M.J., Barbieri, M., Batinić, Bojan, Carrasco, L., Carriazo, S., Gansevoort, R., Martino, G., Raso, F.M., Nistor, I., Ortiz, A., Paolisso, G., Rastenytė, D., Stefan, G., Tedeschi, G., Massy, Z.A., Bikbov, B., Endlich, K.H., Godefroy, O., Chillon, J.-M., Kossioni, A., Kurganaite, J., Perico, N., Remuzzi, G., Grodzicki, T., Trepiccione, F., Zoccali, C., Arici, M., Blankestijn, P., Eckardt, K.-U., Fliser, D., Jiménez, E., König, M., Rychlik, I., Deleidi, M., Reusz, G., "The need for a multi-disciplinary reflection about frailty and cognitive impairment in chronic kidney disease" in Nephrology Dialysis Transplantation, 38, no. 5 (2023):1064-1066,
https://doi.org/10.1093/ndt/gfac334 . .

TY  - CONF
AU  - Mirković, Kristina
AU  - Aranđelović, Jovana
AU  - Kojić, Jana
AU  - Stevanović, Vladimir
AU  - Batinić, Bojan
AU  - Todorović, Vanja
AU  - Đoković, Jelena
AU  - Santrač, Anja
AU  - Major, Tamara
AU  - Savić, Miroslav
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5521
AB  - Introduction: Ciprofloxacin is a fluoroquinolone antibiotic commonly used to treat various bacterial infections, with a potential to induce adverse mood effects in patients. Since the molecular mechanism of ciprofloxacin-induced neurotoxicity is poorly understood, we aimed to identify behavioral changes and corresponding neurotransmitter pattern after its prolonged administration in rats. We screened for untoward effects of ciprofloxacin on locomotor activity, despair, anhedonia, object recognition memory, and anxiety, as behavioral domains affected in various psychiatric diseases. Methodology: Three-month old male Sprague-Dawley rats were orally gavaged with ciprofloxacin (20 or 100 mg/kg) or solvent (0.5% methyl cellulose solution) each day for 4 weeks (n=80). One group of animals (n=40) passed the open field (OF), novel object recognition test (NORT), and forced swimming test (FST). Another group (n=40) underwent elevated plus maze (EPM) and sucrose preference test (SPT). After the completion of behavioral battery, the prefrontal cortex and cerebrospinal fluid (CSF) were collected. The neurotransmitters and metabolites of the kynurenine pathway were determined in the prefrontal cortex (PFC) through HPLC-MS/MS. Additionally, levels of interleukin-2 (IL-2) in CSF were quantified with Luminex. Behavioral and molecular parameters were analyzed by one-way ANOVA followed by Dunnett post hoc test in GraphPad Prism 9. Results: In FST, the treatment with high dose of ciprofloxacin decreased the swim time compared to control, which could be related to induction of despair-like behavior (p<0.05). The ciprofloxacin treatment did not affect object memory in NORT. In OF, the distance travelled and the number of rotations were not changed after treatment with ciprofloxacin compared to the control group. Further, animals treated with ciprofloxacin did not show changes in parameters in EPM and SPT. The acetylcholine levels in PFC were increased after ciprofloxacin treatment (p<0.05) in comparison with controls, which could be associated with depressed mood states. In line with that, high dose of ciprofloxacin treatment showed the tendency to decrease and increase levels of GABA and dopamine, respectively, but without reaching the statistical significance (p=0.07 and p=0.06). No changes in kynurenine pathway were observed after the treatment. The IL-2 concentration in CSF was increased after prolonged administration of low dose of ciprofloxacin treatment compared to the control levels (p<0.05), which could imply immunological stimulation of T lymphocytes and potential neuroinflammation. Conclusion: The despair behavior after treatment with high dose of ciprofloxacin was accompanied by increased levels of acetylcholine in PFC. Furthermore, the high dose of ciprofloxacin treatment showed tendency to decrease GABA levels, and increase dopamine levels in PFC, which could be connected to psychiatric adverse effects. Nonetheless, further studies are essential to confirm these neurotransmitter changes. On the other hand, the low dose of ciprofloxacin treatment elicited the increase of IL-2, which could be a marker of neuroinflammation-related neurotoxicity. In the future, efforts should be made to examine the role of IL-2 in the interaction of the immune system and the central nervous system, as its potential significance as a biomarker.
PB  - European College of Neuropsychopharmacology (ECNP)
C3  - 36th ECPN congress, 7th -10th October 2023, Barcelona, Spain
T1  - Deciphering ciprofloxacin-induced neurotoxicity: behavioral and molecular profiling of ciprofloxacin treatment in rats
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5521
ER  - 

@conference{
author = "Mirković, Kristina and Aranđelović, Jovana and Kojić, Jana and Stevanović, Vladimir and Batinić, Bojan and Todorović, Vanja and Đoković, Jelena and Santrač, Anja and Major, Tamara and Savić, Miroslav",
year = "2023",
abstract = "Introduction: Ciprofloxacin is a fluoroquinolone antibiotic commonly used to treat various bacterial infections, with a potential to induce adverse mood effects in patients. Since the molecular mechanism of ciprofloxacin-induced neurotoxicity is poorly understood, we aimed to identify behavioral changes and corresponding neurotransmitter pattern after its prolonged administration in rats. We screened for untoward effects of ciprofloxacin on locomotor activity, despair, anhedonia, object recognition memory, and anxiety, as behavioral domains affected in various psychiatric diseases. Methodology: Three-month old male Sprague-Dawley rats were orally gavaged with ciprofloxacin (20 or 100 mg/kg) or solvent (0.5% methyl cellulose solution) each day for 4 weeks (n=80). One group of animals (n=40) passed the open field (OF), novel object recognition test (NORT), and forced swimming test (FST). Another group (n=40) underwent elevated plus maze (EPM) and sucrose preference test (SPT). After the completion of behavioral battery, the prefrontal cortex and cerebrospinal fluid (CSF) were collected. The neurotransmitters and metabolites of the kynurenine pathway were determined in the prefrontal cortex (PFC) through HPLC-MS/MS. Additionally, levels of interleukin-2 (IL-2) in CSF were quantified with Luminex. Behavioral and molecular parameters were analyzed by one-way ANOVA followed by Dunnett post hoc test in GraphPad Prism 9. Results: In FST, the treatment with high dose of ciprofloxacin decreased the swim time compared to control, which could be related to induction of despair-like behavior (p<0.05). The ciprofloxacin treatment did not affect object memory in NORT. In OF, the distance travelled and the number of rotations were not changed after treatment with ciprofloxacin compared to the control group. Further, animals treated with ciprofloxacin did not show changes in parameters in EPM and SPT. The acetylcholine levels in PFC were increased after ciprofloxacin treatment (p<0.05) in comparison with controls, which could be associated with depressed mood states. In line with that, high dose of ciprofloxacin treatment showed the tendency to decrease and increase levels of GABA and dopamine, respectively, but without reaching the statistical significance (p=0.07 and p=0.06). No changes in kynurenine pathway were observed after the treatment. The IL-2 concentration in CSF was increased after prolonged administration of low dose of ciprofloxacin treatment compared to the control levels (p<0.05), which could imply immunological stimulation of T lymphocytes and potential neuroinflammation. Conclusion: The despair behavior after treatment with high dose of ciprofloxacin was accompanied by increased levels of acetylcholine in PFC. Furthermore, the high dose of ciprofloxacin treatment showed tendency to decrease GABA levels, and increase dopamine levels in PFC, which could be connected to psychiatric adverse effects. Nonetheless, further studies are essential to confirm these neurotransmitter changes. On the other hand, the low dose of ciprofloxacin treatment elicited the increase of IL-2, which could be a marker of neuroinflammation-related neurotoxicity. In the future, efforts should be made to examine the role of IL-2 in the interaction of the immune system and the central nervous system, as its potential significance as a biomarker.",
publisher = "European College of Neuropsychopharmacology (ECNP)",
journal = "36th ECPN congress, 7th -10th October 2023, Barcelona, Spain",
title = "Deciphering ciprofloxacin-induced neurotoxicity: behavioral and molecular profiling of ciprofloxacin treatment in rats",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5521"
}

Mirković, K., Aranđelović, J., Kojić, J., Stevanović, V., Batinić, B., Todorović, V., Đoković, J., Santrač, A., Major, T.,& Savić, M.. (2023). Deciphering ciprofloxacin-induced neurotoxicity: behavioral and molecular profiling of ciprofloxacin treatment in rats. in 36th ECPN congress, 7th -10th October 2023, Barcelona, Spain
European College of Neuropsychopharmacology (ECNP)..
https://hdl.handle.net/21.15107/rcub_farfar_5521

Mirković K, Aranđelović J, Kojić J, Stevanović V, Batinić B, Todorović V, Đoković J, Santrač A, Major T, Savić M. Deciphering ciprofloxacin-induced neurotoxicity: behavioral and molecular profiling of ciprofloxacin treatment in rats. in 36th ECPN congress, 7th -10th October 2023, Barcelona, Spain. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5521 .

Mirković, Kristina, Aranđelović, Jovana, Kojić, Jana, Stevanović, Vladimir, Batinić, Bojan, Todorović, Vanja, Đoković, Jelena, Santrač, Anja, Major, Tamara, Savić, Miroslav, "Deciphering ciprofloxacin-induced neurotoxicity: behavioral and molecular profiling of ciprofloxacin treatment in rats" in 36th ECPN congress, 7th -10th October 2023, Barcelona, Spain (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5521 .

TY  - CONF
AU  - Živančević, Katarina
AU  - Baralić, Katarina
AU  - Vukelić, Dragana
AU  - Marić, Đurđica
AU  - Kotur-Stevuljević, Jelena
AU  - Ivanišević, Jasmina
AU  - Savić, Miroslav
AU  - Batinić, Bojan
AU  - Janković, Radmila
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5424
AB  - Izloženost olovu (Pb), kadmijumu (Cd), živi (Hg) i arsenu (As) iz životne sredine, kako pojedinačno tako
i njihovim smešama jedan je od faktora za razvoj brojnih zdravstvenih poremećaja, među kojima su i
štetni efekti na nivou centralnog nervnog sistema. ...
AB  - Lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) are top ranked toxic metal(oid)s on the list of
the most important environmental pollutants from the aspect of public health. Literature data show
that exposure to individual metals, as well as their mixtures, is one of the factors for numerous health
disorders development, including adverse effects on the central nervous system. ...
PB  - Udruženje toksikologa Srbije
C3  - 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
T1  - Neurotoksičnost smeše niskih doza olova, kadmijuma, žive i arsena značajnih za izloženost iz životne sredine
T1  - Neurotoxicity of lead, cadmium, mercury and arsenic low dosed mixtures relevant to environmental exposure
SP  - 37
EP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5424
ER  - 

@conference{
author = "Živančević, Katarina and Baralić, Katarina and Vukelić, Dragana and Marić, Đurđica and Kotur-Stevuljević, Jelena and Ivanišević, Jasmina and Savić, Miroslav and Batinić, Bojan and Janković, Radmila and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "Izloženost olovu (Pb), kadmijumu (Cd), živi (Hg) i arsenu (As) iz životne sredine, kako pojedinačno tako
i njihovim smešama jedan je od faktora za razvoj brojnih zdravstvenih poremećaja, među kojima su i
štetni efekti na nivou centralnog nervnog sistema. ..., Lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) are top ranked toxic metal(oid)s on the list of
the most important environmental pollutants from the aspect of public health. Literature data show
that exposure to individual metals, as well as their mixtures, is one of the factors for numerous health
disorders development, including adverse effects on the central nervous system. ...",
publisher = "Udruženje toksikologa Srbije",
journal = "13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book",
title = "Neurotoksičnost smeše niskih doza olova, kadmijuma, žive i arsena značajnih za izloženost iz životne sredine, Neurotoxicity of lead, cadmium, mercury and arsenic low dosed mixtures relevant to environmental exposure",
pages = "37-38",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5424"
}

Živančević, K., Baralić, K., Vukelić, D., Marić, Đ., Kotur-Stevuljević, J., Ivanišević, J., Savić, M., Batinić, B., Janković, R., Buha-Đorđević, A., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2023). Neurotoksičnost smeše niskih doza olova, kadmijuma, žive i arsena značajnih za izloženost iz životne sredine. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book
Udruženje toksikologa Srbije., 37-38.
https://hdl.handle.net/21.15107/rcub_farfar_5424

Živančević K, Baralić K, Vukelić D, Marić Đ, Kotur-Stevuljević J, Ivanišević J, Savić M, Batinić B, Janković R, Buha-Đorđević A, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Neurotoksičnost smeše niskih doza olova, kadmijuma, žive i arsena značajnih za izloženost iz životne sredine. in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book. 2023;:37-38.
https://hdl.handle.net/21.15107/rcub_farfar_5424 .

Živančević, Katarina, Baralić, Katarina, Vukelić, Dragana, Marić, Đurđica, Kotur-Stevuljević, Jelena, Ivanišević, Jasmina, Savić, Miroslav, Batinić, Bojan, Janković, Radmila, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Neurotoksičnost smeše niskih doza olova, kadmijuma, žive i arsena značajnih za izloženost iz životne sredine" in 13th international congress of the Serbian society of toxicology & 1st toxSEE regional conference, 10-12 May, 2023, Belgrade, Abstract Book (2023):37-38,
https://hdl.handle.net/21.15107/rcub_farfar_5424 .

TY  - JOUR
AU  - Aranđelović, Jovana
AU  - Santrač, Anja
AU  - Batinić, Bojan
AU  - Todorović, Lidija
AU  - Stevanović, Vladimir
AU  - Tiruveedhula, Veera Venkata Naga Phani Babu
AU  - Sharmin, Dishary
AU  - Rashid, Farjana
AU  - Stanojević, Boban
AU  - Cook, James
AU  - Savić, Miroslav
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4203
AB  - Aims: GABAergic modulation involved in cognitive processing appears to be substan- tially changed in Alzheimer's disease (AD). In a widely used 5xFAD model of AD, we aimed to assess if negative and positive allosteric modulators of α5 GABA A receptors (NAM and PAM, respectively) would affect social interaction, social, object and spatial memory, and neuroinflammation. Methods: After 10-day treatment with PAM, NAM, or solvent, 6-month-old trans- genic and non-transgenic 5xFAD mice underwent testing in a behavioral battery. Gene expressions of IL-1β, IL-6, TNF-α, GFAP, and IBA-1 were determined in hippocampus and prefrontal cortex by qPCR. Results: PAM treatment impaired spatial learning in transgenic females compared to solvent-treated transgenic females, and social recognition in transgenic and non- transgenic males. NAM treatment declined social interaction in transgenic and non- transgenic males, while had beneficial effect on cognitive flexibility in non-transgenic males compared to solvent-treated non-transgenic males. Transgenic animals have not fully displayed cognitive symptoms, but neuroinflammation was confirmed. NAM reduced proinflammatory gene expressions in transgenic females and astrogliosis in transgenic males compared to pathological controls. Conclusion: PAM and NAM failed to exert favorable behavioral effects in transgenic animals. Suppression of neuroinflammation obtained with NAM calls for more studies with GABAergic ligands in amyloid beta- and/or tau-dependent models with promi- nent neuroinflammation.
PB  - John Wiley and Sons Inc
T2  - CNS Neuroscience & Therapeutics
T1  - Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease
VL  - 28
IS  - 11
SP  - 1767
EP  - 1778
DO  - 10.1111/cns.13914
ER  - 

@article{
author = "Aranđelović, Jovana and Santrač, Anja and Batinić, Bojan and Todorović, Lidija and Stevanović, Vladimir and Tiruveedhula, Veera Venkata Naga Phani Babu and Sharmin, Dishary and Rashid, Farjana and Stanojević, Boban and Cook, James and Savić, Miroslav",
year = "2022",
abstract = "Aims: GABAergic modulation involved in cognitive processing appears to be substan- tially changed in Alzheimer's disease (AD). In a widely used 5xFAD model of AD, we aimed to assess if negative and positive allosteric modulators of α5 GABA A receptors (NAM and PAM, respectively) would affect social interaction, social, object and spatial memory, and neuroinflammation. Methods: After 10-day treatment with PAM, NAM, or solvent, 6-month-old trans- genic and non-transgenic 5xFAD mice underwent testing in a behavioral battery. Gene expressions of IL-1β, IL-6, TNF-α, GFAP, and IBA-1 were determined in hippocampus and prefrontal cortex by qPCR. Results: PAM treatment impaired spatial learning in transgenic females compared to solvent-treated transgenic females, and social recognition in transgenic and non- transgenic males. NAM treatment declined social interaction in transgenic and non- transgenic males, while had beneficial effect on cognitive flexibility in non-transgenic males compared to solvent-treated non-transgenic males. Transgenic animals have not fully displayed cognitive symptoms, but neuroinflammation was confirmed. NAM reduced proinflammatory gene expressions in transgenic females and astrogliosis in transgenic males compared to pathological controls. Conclusion: PAM and NAM failed to exert favorable behavioral effects in transgenic animals. Suppression of neuroinflammation obtained with NAM calls for more studies with GABAergic ligands in amyloid beta- and/or tau-dependent models with promi- nent neuroinflammation.",
publisher = "John Wiley and Sons Inc",
journal = "CNS Neuroscience & Therapeutics",
title = "Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease",
volume = "28",
number = "11",
pages = "1767-1778",
doi = "10.1111/cns.13914"
}

Aranđelović, J., Santrač, A., Batinić, B., Todorović, L., Stevanović, V., Tiruveedhula, V. V. N. P. B., Sharmin, D., Rashid, F., Stanojević, B., Cook, J.,& Savić, M.. (2022). Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease. in CNS Neuroscience & Therapeutics
John Wiley and Sons Inc., 28(11), 1767-1778.
https://doi.org/10.1111/cns.13914

Aranđelović J, Santrač A, Batinić B, Todorović L, Stevanović V, Tiruveedhula VVNPB, Sharmin D, Rashid F, Stanojević B, Cook J, Savić M. Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease. in CNS Neuroscience & Therapeutics. 2022;28(11):1767-1778.
doi:10.1111/cns.13914 .

Aranđelović, Jovana, Santrač, Anja, Batinić, Bojan, Todorović, Lidija, Stevanović, Vladimir, Tiruveedhula, Veera Venkata Naga Phani Babu, Sharmin, Dishary, Rashid, Farjana, Stanojević, Boban, Cook, James, Savić, Miroslav, "Effects of α5 GABAA receptor modulation on social interaction, memory, and neuroinflammation in a mouse model of Alzheimer's disease" in CNS Neuroscience & Therapeutics, 28, no. 11 (2022):1767-1778,
https://doi.org/10.1111/cns.13914 . .

TY  - JOUR
AU  - Santrač, Anja
AU  - Bijelić, Dunja
AU  - Stevanović, Vladimir
AU  - Banićević, Marija
AU  - Aranđelović, Jovana
AU  - Batinić, Bojan
AU  - Sharmin, Dishary
AU  - Cook, James
AU  - Savić, Miroslav
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4071
AB  - Autism spectrum disorder (ASD), as a common neurodevelopmental disorder that encompasses impairments in social communication and interaction, as well as repetitive and restrictive behavior, still awaits an effective treatment strategy. The involvement of GABAergic neurotransmission, and especially a deficit of GABA A receptors that contain the α5 subunits, were implicated in pathogenesis of ASD. Therefore, we tested MP-III-022, a positive allosteric modulator (PAM) selective for α5GABAA receptors, in Wistar rats prenatally exposed to valproic acid, as an animal model useful for studying ASD. Postweaning rats of both sexes were treated for 7 days with vehicle or MP-III-022 at two doses pharmacokinetically determined as selective, and thereafter tested in a behavioral battery (social interaction test, elevated plus maze, spontaneous locomotor activ- ity, and standard and reverse Morris water maze). Additional rats were used for establishing a primary neuronal culture and performing calcium imaging, and determination of hippocampal mRNA levels of GABRA5, NKCC1, and KCC2. MP-III-022 prevented impairments in many parameters connected with social, repetitive and restrictive behavioral domains. The lower and higher dose was more effective in males and females, respectively. Intriguingly, MP-III-022 elicited certain changes in control animals similar to those manifested in valproate ani- mals themselves. Behavioral results were mirrored in GABA switch and spontane- ous neuronal activity, assessed with calcium imaging, and also in expression changes of three genes analyzed. Our data support a role of α5GABAA receptors in pathophysiology of ASD, and suggest a potential application of selective PAMs in its treatment, that needs to be researched in a sex-specific manner.
PB  - John Wiley and Sons Inc
T2  - Autism Research
T1  - Postweaning positive modulation of α5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner
DO  - 10.1002/aur.2699
ER  - 

@article{
author = "Santrač, Anja and Bijelić, Dunja and Stevanović, Vladimir and Banićević, Marija and Aranđelović, Jovana and Batinić, Bojan and Sharmin, Dishary and Cook, James and Savić, Miroslav",
year = "2022",
abstract = "Autism spectrum disorder (ASD), as a common neurodevelopmental disorder that encompasses impairments in social communication and interaction, as well as repetitive and restrictive behavior, still awaits an effective treatment strategy. The involvement of GABAergic neurotransmission, and especially a deficit of GABA A receptors that contain the α5 subunits, were implicated in pathogenesis of ASD. Therefore, we tested MP-III-022, a positive allosteric modulator (PAM) selective for α5GABAA receptors, in Wistar rats prenatally exposed to valproic acid, as an animal model useful for studying ASD. Postweaning rats of both sexes were treated for 7 days with vehicle or MP-III-022 at two doses pharmacokinetically determined as selective, and thereafter tested in a behavioral battery (social interaction test, elevated plus maze, spontaneous locomotor activ- ity, and standard and reverse Morris water maze). Additional rats were used for establishing a primary neuronal culture and performing calcium imaging, and determination of hippocampal mRNA levels of GABRA5, NKCC1, and KCC2. MP-III-022 prevented impairments in many parameters connected with social, repetitive and restrictive behavioral domains. The lower and higher dose was more effective in males and females, respectively. Intriguingly, MP-III-022 elicited certain changes in control animals similar to those manifested in valproate ani- mals themselves. Behavioral results were mirrored in GABA switch and spontane- ous neuronal activity, assessed with calcium imaging, and also in expression changes of three genes analyzed. Our data support a role of α5GABAA receptors in pathophysiology of ASD, and suggest a potential application of selective PAMs in its treatment, that needs to be researched in a sex-specific manner.",
publisher = "John Wiley and Sons Inc",
journal = "Autism Research",
title = "Postweaning positive modulation of α5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner",
doi = "10.1002/aur.2699"
}

Santrač, A., Bijelić, D., Stevanović, V., Banićević, M., Aranđelović, J., Batinić, B., Sharmin, D., Cook, J.,& Savić, M.. (2022). Postweaning positive modulation of α5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner. in Autism Research
John Wiley and Sons Inc..
https://doi.org/10.1002/aur.2699

Santrač A, Bijelić D, Stevanović V, Banićević M, Aranđelović J, Batinić B, Sharmin D, Cook J, Savić M. Postweaning positive modulation of α5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner. in Autism Research. 2022;.
doi:10.1002/aur.2699 .

Santrač, Anja, Bijelić, Dunja, Stevanović, Vladimir, Banićević, Marija, Aranđelović, Jovana, Batinić, Bojan, Sharmin, Dishary, Cook, James, Savić, Miroslav, "Postweaning positive modulation of α5GABAA receptors improves autism-like features in prenatal valproate rat model in a sex-specific manner" in Autism Research (2022),
https://doi.org/10.1002/aur.2699 . .

TY  - JOUR
AU  - Santrač, Anja
AU  - Batinić, Bojan
AU  - Timić-Stamenić, Tamara
AU  - Aranđelović, Jovana
AU  - Sharmin, Dishary
AU  - Knutson, Daniel E.
AU  - Cook, James
AU  - Savić, Miroslav
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3968
AB  - Positive allosteric modulators (PAMs) of α5GABAA receptors (α5GABAARs) are emerging as potential therapeutics for a range of neuropsychiatric disorders. However, their role in memory processing of healthy animals is not sufficiently examined. We tested the effects of MP-III-022 (1 mg/kg, 2.5 mg/kg and 10 mg/kg), a PAM known to be selective for α5GABAARs and devoid of prominent side-effects, in different behavioral paradigms (Morris water maze, novel object recognition test and social novelty discrimination) and on GABRA5 expression in Wistar rats, 30 min and 24 h after intraperitoneal treatment administration. The lowest dose tested worsened short-term object memory. The same dose, administered two times in a span of 24 h, improved spatial and impaired object and, at a trend level, social memory. The highest dose had a detrimental effect on all types of long-term memory (object memory at a trend level) and short-term spatial memory, but improved short-term object and social memory. Distinct sets of expression changes were detected in both prefrontal cortex and two regions of the hippocampus, but the latter ones could be assessed as more consequential. An increase of GABRA5 mRNA in CA2 occurred in parallel with improvement of object and social, but impairment of spatial memory, while the opposite happened with a trend level change in CA1. Our study demonstrates the variability of the roles of the α5GABAAR based on its level of expression and localization, in dependence on the type and protocol of cognitive tasks, as well as the respective timing of pharmacological modulation and testing.
PB  - Elsevier B.V.
T2  - Behavioural Brain Research
T1  - Positive modulation of α5GABAA receptors leads to dichotomous effects in rats on memory pattern and GABRA5 expression in prefrontal cortex and hippocampus
VL  - 416
DO  - 10.1016/j.bbr.2021.113578
ER  - 

@article{
author = "Santrač, Anja and Batinić, Bojan and Timić-Stamenić, Tamara and Aranđelović, Jovana and Sharmin, Dishary and Knutson, Daniel E. and Cook, James and Savić, Miroslav",
year = "2022",
abstract = "Positive allosteric modulators (PAMs) of α5GABAA receptors (α5GABAARs) are emerging as potential therapeutics for a range of neuropsychiatric disorders. However, their role in memory processing of healthy animals is not sufficiently examined. We tested the effects of MP-III-022 (1 mg/kg, 2.5 mg/kg and 10 mg/kg), a PAM known to be selective for α5GABAARs and devoid of prominent side-effects, in different behavioral paradigms (Morris water maze, novel object recognition test and social novelty discrimination) and on GABRA5 expression in Wistar rats, 30 min and 24 h after intraperitoneal treatment administration. The lowest dose tested worsened short-term object memory. The same dose, administered two times in a span of 24 h, improved spatial and impaired object and, at a trend level, social memory. The highest dose had a detrimental effect on all types of long-term memory (object memory at a trend level) and short-term spatial memory, but improved short-term object and social memory. Distinct sets of expression changes were detected in both prefrontal cortex and two regions of the hippocampus, but the latter ones could be assessed as more consequential. An increase of GABRA5 mRNA in CA2 occurred in parallel with improvement of object and social, but impairment of spatial memory, while the opposite happened with a trend level change in CA1. Our study demonstrates the variability of the roles of the α5GABAAR based on its level of expression and localization, in dependence on the type and protocol of cognitive tasks, as well as the respective timing of pharmacological modulation and testing.",
publisher = "Elsevier B.V.",
journal = "Behavioural Brain Research",
title = "Positive modulation of α5GABAA receptors leads to dichotomous effects in rats on memory pattern and GABRA5 expression in prefrontal cortex and hippocampus",
volume = "416",
doi = "10.1016/j.bbr.2021.113578"
}

Santrač, A., Batinić, B., Timić-Stamenić, T., Aranđelović, J., Sharmin, D., Knutson, D. E., Cook, J.,& Savić, M.. (2022). Positive modulation of α5GABAA receptors leads to dichotomous effects in rats on memory pattern and GABRA5 expression in prefrontal cortex and hippocampus. in Behavioural Brain Research
Elsevier B.V.., 416.
https://doi.org/10.1016/j.bbr.2021.113578

Santrač A, Batinić B, Timić-Stamenić T, Aranđelović J, Sharmin D, Knutson DE, Cook J, Savić M. Positive modulation of α5GABAA receptors leads to dichotomous effects in rats on memory pattern and GABRA5 expression in prefrontal cortex and hippocampus. in Behavioural Brain Research. 2022;416.
doi:10.1016/j.bbr.2021.113578 .

Santrač, Anja, Batinić, Bojan, Timić-Stamenić, Tamara, Aranđelović, Jovana, Sharmin, Dishary, Knutson, Daniel E., Cook, James, Savić, Miroslav, "Positive modulation of α5GABAA receptors leads to dichotomous effects in rats on memory pattern and GABRA5 expression in prefrontal cortex and hippocampus" in Behavioural Brain Research, 416 (2022),
https://doi.org/10.1016/j.bbr.2021.113578 . .

TY  - JOUR
AU  - Javorac, Dragana
AU  - Anđelković, Milena
AU  - Repić, Aleksandra
AU  - Tatović, Simona
AU  - Buha-Đorđević, Aleksandra
AU  - Antonijević-Miljaković, Evica
AU  - Batinić, Bojan
AU  - Boričić, Novica
AU  - Đukić-Ćosić, Danijela
AU  - Antonijević, Biljana
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4089
AB  - Lead (Pb) is a toxic metal that affects almost all human’s system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis
VL  - 360
DO  - 10.1016/j.cbi.2022.109932
ER  - 

@article{
author = "Javorac, Dragana and Anđelković, Milena and Repić, Aleksandra and Tatović, Simona and Buha-Đorđević, Aleksandra and Antonijević-Miljaković, Evica and Batinić, Bojan and Boričić, Novica and Đukić-Ćosić, Danijela and Antonijević, Biljana and Bulat, Zorica",
year = "2022",
abstract = "Lead (Pb) is a toxic metal that affects almost all human’s system and organs, with the nervous system as the most sensitive. Better understanding of the Pb neurobehavioral effects and neurotoxicity requires realistic study scenarios based on low level exposure. The aim of this study was to determine neurotoxic effects and mechanisms of Pb in six low doses and to establish dose-response relationship for these effects and related Benchmark dose (BMD). Forty-two, male albino Wistar rats were randomized into seven groups, control and Pb-exposed: 0.1, 0.5, 1, 3, 7 and 15 mg Pb/kg body weight/day (oral gavage) for 28 days. Behavioural tests (Elevated plus maze test, Spontaneous locomotor activity test and Novel object recognition test) were conducted in the last week of experiment, in the control, lower (0.5 mg Pb/kg), middle (3 mg Pb/kg) and higher (15 mg Pb/kg) dose groups. The acetylcholinesterase activity, oxidative status and essential elements levels (Cu, Zn, Mn and Fe) were measured in brain tissue along with histological analyses. External and internal dose-response analyses were performed using PROASTweb 70.1 software. The results have shown that subacute exposure to very low doses of Pb resulted in memory deficits in rats that was accompanied with acetylcholinesterase enzyme activity decrease. The observed hyperactive behaviour was accompanied by dose-dependent induction of brain oxidative stress and Zn elevation. The histological alterations in Purkinje cells were only detected in the group treated with the highest Pb dose. The lowest BMD considering entire oxidative status was calculated based on total oxidative status (4.5e-06 mg Pb/kg b.w./day). The findings reported in our study may be beneficial in further evaluating the health consequences and human health risk assessment of low-level Pb exposure.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis",
volume = "360",
doi = "10.1016/j.cbi.2022.109932"
}

Javorac, D., Anđelković, M., Repić, A., Tatović, S., Buha-Đorđević, A., Antonijević-Miljaković, E., Batinić, B., Boričić, N., Đukić-Ćosić, D., Antonijević, B.,& Bulat, Z.. (2022). Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 360.
https://doi.org/10.1016/j.cbi.2022.109932

Javorac D, Anđelković M, Repić A, Tatović S, Buha-Đorđević A, Antonijević-Miljaković E, Batinić B, Boričić N, Đukić-Ćosić D, Antonijević B, Bulat Z. Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis. in Chemico-Biological Interactions. 2022;360.
doi:10.1016/j.cbi.2022.109932 .

Javorac, Dragana, Anđelković, Milena, Repić, Aleksandra, Tatović, Simona, Buha-Đorđević, Aleksandra, Antonijević-Miljaković, Evica, Batinić, Bojan, Boričić, Novica, Đukić-Ćosić, Danijela, Antonijević, Biljana, Bulat, Zorica, "Comprehensive insight into the neurotoxic mechanisms of low dose Pb exposure in Wistar rats: Benchmark dose analysis" in Chemico-Biological Interactions, 360 (2022),
https://doi.org/10.1016/j.cbi.2022.109932 . .

TY  - CONF
AU  - Manojlović, Marina
AU  - Milosavljević, Filip
AU  - Atanasov, Andrea
AU  - Batinić, Bojan
AU  - Sitarica, Pavle
AU  - Jukić, Marin
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4728
AB  - Background: Due to the COVID-19 pandemic, the prevalence of anxiety and
depression disorders increased by approximately 25-30% [1]. Reasons behind
this are likely associated with the increased average daily level of stress, especially during social isolation. Since one of the main adolescence hallmarks is
formation of meaningful social and love relationships, it represents a particularly
vulnerable period for social stress [2]. The aim of this study was to evaluate
whether isolation stress during the adolescence causes general and social anxiety
in rats.
Methods: Sprague-Dawley rats of both sexes were used for the adolescence social
isolation experiment. From the fourth postnatal week, 24 rats were single caged
and therefore subjected to the social isolation stress, while 24 non-stressed
control rats remained in groups of four per cage and were handled three times a
week. All rats were handled daily for one week and weighted before behavioural
tests. From eleventh week, rats were subjected to the open field, elevated plus
maze, and three-chamber sociability tests, with two-day gap between different
tests. In open field test, time spent in the centre was measured, while in the
elevated plus maze test, the time spent in open arms, normalized to time spent in
all arms was measured; reduction in values of these parameters was interpreted
as general anxiety. In the social preference test, social preference ratio was
calculated for each animal, according to the previously published protocol [3],
and reduction in this ratio was interpreted as social anxiety. 2-way ANOVA, with
sex and isolation stress as factors, was used for parametric data analysis, and
Fischer’s post hoc test was used to detect statistically significant between group
differences. Kruskal-Wallis test was used for non-parametric data analysis, and
Mann-Whitney post hoc test with multiple comparison correction was used to
detect statistically significant between group differences.
Results: Compared to control rats, time spent in the centre of open field (-44%
[95%CI: -76%, -12%] p¼0,008) and total distance travelled (-17% [95%CI:
-32%, -2%], p¼0.028) were decreased in isolated males, but not in females
(p>0.1). In elevated plus maze test, time spent in the open arms was significantly
decreased in male isolated rats (isolated: [median: 0.76, IQR: 0.00 – 2.06] vs
control: [median: 4.96, IQR: 2.04 – 17.75], p¼0.034); however, this change did
not remain significant after multiple comparisons corrections. In sociability tests,
both male and female isolated rats exhibited increase in social preference ratio
(+32% [95%CI: 12%, 51%], p¼0.002) and preference for novel animal over
familiar one (+48% [95%CI: 10%, 86%], p¼0.015), compared to control rats.
Body weight, measured after six weeks of social isolation at week ten, was
increased in isolated male compared to control rats (+19% [95%CI: 14%, 24%],
p<0.001), while there was no such difference observed in female rats.
Conclusion: Social isolation caused increase in general anxiety in male, but not
female rats. In addition, both male and female rats exhibited robust increase in
preference for social interaction and novel social stimulus, which is the result
opposite from the expected social anxiety as initially hypothesized.
PB  - Elsevier
C3  - Neuroscience Applied
T1  - Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats
VL  - 1
IS  - Supplement 2
SP  - 19
EP  - 19
DO  - 10.1016/j.nsa.2022.100149
ER  - 

@conference{
author = "Manojlović, Marina and Milosavljević, Filip and Atanasov, Andrea and Batinić, Bojan and Sitarica, Pavle and Jukić, Marin",
year = "2022",
abstract = "Background: Due to the COVID-19 pandemic, the prevalence of anxiety and
depression disorders increased by approximately 25-30% [1]. Reasons behind
this are likely associated with the increased average daily level of stress, especially during social isolation. Since one of the main adolescence hallmarks is
formation of meaningful social and love relationships, it represents a particularly
vulnerable period for social stress [2]. The aim of this study was to evaluate
whether isolation stress during the adolescence causes general and social anxiety
in rats.
Methods: Sprague-Dawley rats of both sexes were used for the adolescence social
isolation experiment. From the fourth postnatal week, 24 rats were single caged
and therefore subjected to the social isolation stress, while 24 non-stressed
control rats remained in groups of four per cage and were handled three times a
week. All rats were handled daily for one week and weighted before behavioural
tests. From eleventh week, rats were subjected to the open field, elevated plus
maze, and three-chamber sociability tests, with two-day gap between different
tests. In open field test, time spent in the centre was measured, while in the
elevated plus maze test, the time spent in open arms, normalized to time spent in
all arms was measured; reduction in values of these parameters was interpreted
as general anxiety. In the social preference test, social preference ratio was
calculated for each animal, according to the previously published protocol [3],
and reduction in this ratio was interpreted as social anxiety. 2-way ANOVA, with
sex and isolation stress as factors, was used for parametric data analysis, and
Fischer’s post hoc test was used to detect statistically significant between group
differences. Kruskal-Wallis test was used for non-parametric data analysis, and
Mann-Whitney post hoc test with multiple comparison correction was used to
detect statistically significant between group differences.
Results: Compared to control rats, time spent in the centre of open field (-44%
[95%CI: -76%, -12%] p¼0,008) and total distance travelled (-17% [95%CI:
-32%, -2%], p¼0.028) were decreased in isolated males, but not in females
(p>0.1). In elevated plus maze test, time spent in the open arms was significantly
decreased in male isolated rats (isolated: [median: 0.76, IQR: 0.00 – 2.06] vs
control: [median: 4.96, IQR: 2.04 – 17.75], p¼0.034); however, this change did
not remain significant after multiple comparisons corrections. In sociability tests,
both male and female isolated rats exhibited increase in social preference ratio
(+32% [95%CI: 12%, 51%], p¼0.002) and preference for novel animal over
familiar one (+48% [95%CI: 10%, 86%], p¼0.015), compared to control rats.
Body weight, measured after six weeks of social isolation at week ten, was
increased in isolated male compared to control rats (+19% [95%CI: 14%, 24%],
p<0.001), while there was no such difference observed in female rats.
Conclusion: Social isolation caused increase in general anxiety in male, but not
female rats. In addition, both male and female rats exhibited robust increase in
preference for social interaction and novel social stimulus, which is the result
opposite from the expected social anxiety as initially hypothesized.",
publisher = "Elsevier",
journal = "Neuroscience Applied",
title = "Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats",
volume = "1",
number = "Supplement 2",
pages = "19-19",
doi = "10.1016/j.nsa.2022.100149"
}

Manojlović, M., Milosavljević, F., Atanasov, A., Batinić, B., Sitarica, P.,& Jukić, M.. (2022). Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats. in Neuroscience Applied
Elsevier., 1(Supplement 2), 19-19.
https://doi.org/10.1016/j.nsa.2022.100149

Manojlović M, Milosavljević F, Atanasov A, Batinić B, Sitarica P, Jukić M. Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats. in Neuroscience Applied. 2022;1(Supplement 2):19-19.
doi:10.1016/j.nsa.2022.100149 .

Manojlović, Marina, Milosavljević, Filip, Atanasov, Andrea, Batinić, Bojan, Sitarica, Pavle, Jukić, Marin, "Social adolescent stress causes increased general anxiety in male rats and reduced social anxiety in both male and female rats" in Neuroscience Applied, 1, no. Supplement 2 (2022):19-19,
https://doi.org/10.1016/j.nsa.2022.100149 . .

TY  - JOUR
AU  - Đoković, Jelena
AU  - Savić, Sanela
AU  - Mitrović, Jelena
AU  - Nikolić, Ines
AU  - Marković, Bojan
AU  - Ranđelović, Danijela
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Cekić, Nebojša
AU  - Stevanović, Vladimir
AU  - Batinić, Bojan
AU  - Aranđelović, Jovana
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5541
AB  - The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats
VL  - 22
IS  - 15
DO  - 10.3390/ijms22157991
ER  - 

@article{
author = "Đoković, Jelena and Savić, Sanela and Mitrović, Jelena and Nikolić, Ines and Marković, Bojan and Ranđelović, Danijela and Antić-Stanković, Jelena and Božić, Dragana and Cekić, Nebojša and Stevanović, Vladimir and Batinić, Bojan and Aranđelović, Jovana and Savić, Miroslav and Savić, Snežana",
year = "2021",
abstract = "The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats",
volume = "22",
number = "15",
doi = "10.3390/ijms22157991"
}

Đoković, J., Savić, S., Mitrović, J., Nikolić, I., Marković, B., Ranđelović, D., Antić-Stanković, J., Božić, D., Cekić, N., Stevanović, V., Batinić, B., Aranđelović, J., Savić, M.,& Savić, S.. (2021). Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats. in International Journal of Molecular Sciences
MDPI., 22(15).
https://doi.org/10.3390/ijms22157991

Đoković J, Savić S, Mitrović J, Nikolić I, Marković B, Ranđelović D, Antić-Stanković J, Božić D, Cekić N, Stevanović V, Batinić B, Aranđelović J, Savić M, Savić S. Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats. in International Journal of Molecular Sciences. 2021;22(15).
doi:10.3390/ijms22157991 .

Đoković, Jelena, Savić, Sanela, Mitrović, Jelena, Nikolić, Ines, Marković, Bojan, Ranđelović, Danijela, Antić-Stanković, Jelena, Božić, Dragana, Cekić, Nebojša, Stevanović, Vladimir, Batinić, Bojan, Aranđelović, Jovana, Savić, Miroslav, Savić, Snežana, "Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats" in International Journal of Molecular Sciences, 22, no. 15 (2021),
https://doi.org/10.3390/ijms22157991 . .

TY  - JOUR
AU  - Stanić, Dušanka
AU  - Oved, Keren
AU  - Israel-Elgali, Ifat
AU  - Jukić, Marin
AU  - Batinić, Bojan
AU  - Puškaš, Nela
AU  - Shomron, Noam
AU  - Gurwitz, David
AU  - Pešić, Vesna
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3883
AB  - Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin β3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.
PB  - Elsevier Ltd
T2  - Psychoneuroendocrinology
T1  - Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy
VL  - 129
DO  - 10.1016/j.psyneuen.2021.105234
ER  - 

@article{
author = "Stanić, Dušanka and Oved, Keren and Israel-Elgali, Ifat and Jukić, Marin and Batinić, Bojan and Puškaš, Nela and Shomron, Noam and Gurwitz, David and Pešić, Vesna",
year = "2021",
abstract = "Intranasal treatment with oxytocin showed beneficial effects in post-traumatic stress disorder and autism spectrum disorders; however, it was not investigated as much in depression. Keeping in mind the favorable effects of oxytocin on animal models of anxiety and depression, we postulated that synergy between prescribed first choice drugs, selective serotonin reuptake inhibitors (SSRIs) and oxytocin could improve the treatment outcome compared with SSRI monotherapy. Our previous in vitro genome-wide transcriptomic study on human lymphoblastoid cell lines exposed to paroxetine resulted in increase of integrin β3 (ITGB3) gene expression, and further, ITGB3/CHL1 expression ratio was hypothesized to influence the sensitivity to SSRIs. The aim of this report was to explore molecular mechanisms behind the antidepressant-like oxytocin effect, alone and in synergy with citalopram, on behavioral and molecular level in corticosterone treated rats, a paradigm used to model anxiety and depression in animals. Oxytocin treatment (1) ameliorated corticosterone-induced reduction of neurogenesis and number of parvalbumin-positive interneurons in the hippocampal CA1 region, (2) enhanced anxiolytic- and antidepressant-like effects of citalopram in the open field test, and (3) the SSRI/oxytocin synergy persisted in reversing the reduction of the Itgb3 gene expression and increased Itgb3/Chl1 ratio in the prefrontal cortices. These results support the existence of synergy between citalopram and oxytocin in reversing the molecular and behavioral changes induced by corticosterone treatment and point to possible molecular mechanisms behind antidepressant-like effect of oxytocin.",
publisher = "Elsevier Ltd",
journal = "Psychoneuroendocrinology",
title = "Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy",
volume = "129",
doi = "10.1016/j.psyneuen.2021.105234"
}

Stanić, D., Oved, K., Israel-Elgali, I., Jukić, M., Batinić, B., Puškaš, N., Shomron, N., Gurwitz, D.,& Pešić, V.. (2021). Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy. in Psychoneuroendocrinology
Elsevier Ltd., 129.
https://doi.org/10.1016/j.psyneuen.2021.105234

Stanić D, Oved K, Israel-Elgali I, Jukić M, Batinić B, Puškaš N, Shomron N, Gurwitz D, Pešić V. Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy. in Psychoneuroendocrinology. 2021;129.
doi:10.1016/j.psyneuen.2021.105234 .

Stanić, Dušanka, Oved, Keren, Israel-Elgali, Ifat, Jukić, Marin, Batinić, Bojan, Puškaš, Nela, Shomron, Noam, Gurwitz, David, Pešić, Vesna, "Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: Relevance to sensitivity to SSRI therapy" in Psychoneuroendocrinology, 129 (2021),
https://doi.org/10.1016/j.psyneuen.2021.105234 . .

TY  - JOUR
AU  - Jeremić, Aleksandra
AU  - Milosavljević, Filip
AU  - Vladimirov, Sandra
AU  - Batinić, Bojan
AU  - Marković, Bojan
AU  - Jukić, Marin
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4733
AB  - Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic
drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the
method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was
deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the
mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded
in the MRM mode by using a positive electrospray source with tandem mass spectrometry
detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram
(8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant
concentrations for each drug. Coefficients of determination (R2
) were higher than 0.99, while the
relative difference between nominal and measured concentrations (RE) and CV were lower than
15% for all targets. High performance liquid chromatography coupled with the mass detector
(HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone
366
and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy,
precision, matrix effect and stability. This method has significant advantages in terms of low
sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4
minutes).
AB  - Simultana kvantifikacija većeg broja psihijatrijskih lekova je 
važna za terapijsko praćenje 
psihijatrijskih  pacijenata.  Takođe
,  od  značaja  iz  praktičnih  ra
zloga  bi  bilo  da  metoda  bude 
jednostavna,  laka  za  izvođenje  i 
da  ne  zahteva  puno  vremena.  Uz
orak  plazme  (200  μl)  je 
deproteinizovan i izvršeno je h
romatografsko razdvajanje lekova
 na 
ZORBAX Eclipse XDB-
Phenyl  koloni  sa  mobilnom  fazom  sačinjenom  od  acetonitrila  i  vo
denog  rastvora 
0,1% 
mravlje kiseline
 (
60:40, v/v). Maseni spektri snimani su u MRM modu korišćenjem i
zvora sa 
elektrosprej pozitivnom jonizacijom i tandemske masene detekcij
e. Ispitivani opseg koncentracija 
bio je 2–256 ng/ml za sve analizirane lekove, osim za escitalop
ram, gde je bio 8-256 ng/ml. 
Kontrolni  uzorci  su  pripremani  u
  kvintuplikatu  u  tri  relevantne
  koncentracije  za  svaki  lek. 
Determinacioni koeficijenti (R
2
) bili su veći od 0,99, dok su relativna razlika između nominal
nih 
i merenih koncentracija (RV) i koeficijent varijacije (CV) bili
 manji od 15% za sve analite. 
Metoda  tečne  hromatografije  visoki
h  performansi  uparena  sa  tand
em  masenim  detektorom 
(HPLC-MS/MS) je validirana u pogledu selektivnosti, linearnosti
, tačnosti, preciznosti, efekata 
matriksa  i  stabilnosti  za  simultano  određivanje 
sertralina,  escitaloprama,  risperidona  i 
paliperidona u humanoj plazmi. Metoda zahteva malu zapreminu uz
orka (200 μl), kratke pripreme 
uzorka (3 sata) i kratko vreme tr
ajanja pojedinačnog merenja (4
 minuta).
T2  - Arhiv za farmaciju
T1  - Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma
T1  - Validacija brze i jednostavne hromatografske 
metode za simultanu kvantifikaciju nivoa 
sertralina, escitaloprama, risperidona i 
paliperidona u humanoj plazmi
VL  - 71
IS  - 5
SP  - 365
EP  - 377
DO  - 10.5937/arhfarm71-31163
ER  - 

@article{
author = "Jeremić, Aleksandra and Milosavljević, Filip and Vladimirov, Sandra and Batinić, Bojan and Marković, Bojan and Jukić, Marin",
year = "2021",
abstract = "Simultaneous quantification of multiple psychiatric drugs is important for the therapeutic
drug monitoring of psychiatric patients. In addition, it would be highly advantageous if the
method could be simple, straightforward, and not time-consuming. A 200 µl plasma sample was
deproteinized, drugs were separated by a ZORBAX Eclipse XDB-Phenyl column with the
mobile phase composed of acetonitrile and 0.1 % formic acid in water (60:40, v/v), and recorded
in the MRM mode by using a positive electrospray source with tandem mass spectrometry
detection. The dynamic range was 2–256 ng/ml for all the analyzed drugs, except escitalopram
(8-256 ng/ml). Quality control samples were prepared in quintuplicates in three relevant
concentrations for each drug. Coefficients of determination (R2
) were higher than 0.99, while the
relative difference between nominal and measured concentrations (RE) and CV were lower than
15% for all targets. High performance liquid chromatography coupled with the mass detector
(HPLC-MS/MS) method for simultaneous determination of sertraline, escitalopram, risperidone
366
and paliperidone in human plasma was validated with respect to selectivity, linearity, accuracy,
precision, matrix effect and stability. This method has significant advantages in terms of low
sample volume (200 µl), short preparation time (3 hours) and short runtime per sample (4
minutes)., Simultana kvantifikacija većeg broja psihijatrijskih lekova je 
važna za terapijsko praćenje 
psihijatrijskih  pacijenata.  Takođe
,  od  značaja  iz  praktičnih  ra
zloga  bi  bilo  da  metoda  bude 
jednostavna,  laka  za  izvođenje  i 
da  ne  zahteva  puno  vremena.  Uz
orak  plazme  (200  μl)  je 
deproteinizovan i izvršeno je h
romatografsko razdvajanje lekova
 na 
ZORBAX Eclipse XDB-
Phenyl  koloni  sa  mobilnom  fazom  sačinjenom  od  acetonitrila  i  vo
denog  rastvora 
0,1% 
mravlje kiseline
 (
60:40, v/v). Maseni spektri snimani su u MRM modu korišćenjem i
zvora sa 
elektrosprej pozitivnom jonizacijom i tandemske masene detekcij
e. Ispitivani opseg koncentracija 
bio je 2–256 ng/ml za sve analizirane lekove, osim za escitalop
ram, gde je bio 8-256 ng/ml. 
Kontrolni  uzorci  su  pripremani  u
  kvintuplikatu  u  tri  relevantne
  koncentracije  za  svaki  lek. 
Determinacioni koeficijenti (R
2
) bili su veći od 0,99, dok su relativna razlika između nominal
nih 
i merenih koncentracija (RV) i koeficijent varijacije (CV) bili
 manji od 15% za sve analite. 
Metoda  tečne  hromatografije  visoki
h  performansi  uparena  sa  tand
em  masenim  detektorom 
(HPLC-MS/MS) je validirana u pogledu selektivnosti, linearnosti
, tačnosti, preciznosti, efekata 
matriksa  i  stabilnosti  za  simultano  određivanje 
sertralina,  escitaloprama,  risperidona  i 
paliperidona u humanoj plazmi. Metoda zahteva malu zapreminu uz
orka (200 μl), kratke pripreme 
uzorka (3 sata) i kratko vreme tr
ajanja pojedinačnog merenja (4
 minuta).",
journal = "Arhiv za farmaciju",
title = "Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma, Validacija brze i jednostavne hromatografske 
metode za simultanu kvantifikaciju nivoa 
sertralina, escitaloprama, risperidona i 
paliperidona u humanoj plazmi",
volume = "71",
number = "5",
pages = "365-377",
doi = "10.5937/arhfarm71-31163"
}

Jeremić, A., Milosavljević, F., Vladimirov, S., Batinić, B., Marković, B.,& Jukić, M.. (2021). Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma. in Arhiv za farmaciju, 71(5), 365-377.
https://doi.org/10.5937/arhfarm71-31163

Jeremić A, Milosavljević F, Vladimirov S, Batinić B, Marković B, Jukić M. Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma. in Arhiv za farmaciju. 2021;71(5):365-377.
doi:10.5937/arhfarm71-31163 .

Jeremić, Aleksandra, Milosavljević, Filip, Vladimirov, Sandra, Batinić, Bojan, Marković, Bojan, Jukić, Marin, "Validation of a quick and simple chromatographic method for simultaneous quantification of sertraline, escitalopram, risperidone and paliperidone levels in the human plasma" in Arhiv za farmaciju, 71, no. 5 (2021):365-377,
https://doi.org/10.5937/arhfarm71-31163 . .

TY  - CONF
AU  - Milosavljević, Filip
AU  - Vučić, Marija
AU  - Manojlović, Marina
AU  - Miloševski, Teodora
AU  - Batinić, Bojan
AU  - Novalen, Maria
AU  - Miksys, Sharon
AU  - Tyndale, Rachel
AU  - Ingelman-Sundberg, Magnus
AU  - Pešić, Vesna
AU  - Jukić, Marin
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4753
AB  - Introduction: CYP2C19 transgenic mouse (2C19TG) is generated by the insertion of 12 copies of the human CYP2C19 gene into mouse genome. This animal model is a tool to study the neurodevelopmental role of CYP2C19 in vivo, since this enzyme is expressed in the foetal brains of 2C19TG mice and humans. Previous studies [1,2] showed anxiety and depression-like behaviour in these mice, while the aim of this study was to characterize the motoric function of the 2C19TG mouse.
Methods: Whole brain dopamine concentration was measured in the brain homogenate of 23 adult mice by the HPLC-MS method. Motoric function in 50 mutant and 43 control mice of both genders was tested by the rotarod and beam walking tests. Beam walking test was repeated after treatment with dopaminergic receptor antagonists, Ecopipam (0.1 mg/kg) and Raclopride (0.25 mg/kg) as a follow-up. The sections of 10 6-month old and 8 15-months old mice were stained with anti-tyrosine hydroxylase antibody and the number of dopaminergic neurons was counted on histological slides under microscope. Next, after transcardial perfusion of 30 2C19TG and 30 control mice of both genders with contrast agent (4% Paraformaldehyde, 0.05M Gadoteridole, 0.01M Phosphate buffered saline, pH=7.4), cranium containing the whole brain was scanned overnight by the 9.4T MRI scanner. The volumes of 39 brain regions were quantified according to the mouse brain atlas [3]. Student's t-test and two-way ANOVA were used to evaluate statistical significance of between-group differences.
Results: Adult 2C19TG mice are hyperdopaminergic, as they exhibit 15% increased dopamine concentration (p<0.001). They also show hyperkinetic motoric phenotype with the ataxia-like walking pattern and pathological clasping reflex. In the beam walking test 2C19TG mice had 20% longer beam crossing time (p=0.007) and 60% more paw slips (p<0.001) then the controls, and this motoric impairment could not be improved with antidopaminergic drugs. Both younger and older 2C19TG mice exhibited only a marginal reduction in the number of dopaminergic neurons of both substantia nigra and ventral tegmental area in a subset of coronal sections. This was confirmed by the gadolinium-enhanced neuroimaging that showed no change in substantia nigra volume in 2C19TG mice. On the other hand, significant differences in volume were identified in 11 regions, including cerebellum (-8.3% p<0.001) and striatum (+3.0%, p<0.001), which are the regions connected with the motoric function. The volumetric changes were detected in the hippocampus (-1.3%, p=0.027), amygdala (+2.8%, p<0.001), septum (+3.3%, p=0.014) and nucleus accumbens (+3.5, p=0.004) of 2C19TG mice. These brain regions are involved in emotional and motivational functions.
Conclusion: Ataxia-like motoric phenotype in 2C19TG transgenic mice is probably caused by changes in cerebellum, while hyperdopaminergism is most likely the compensatory adaptation, whereas the changes in the hippocampus, amygdala, septum, and nucleus accumbens may be connected with the mutants’ depression-like phenotype and susceptibility to stress. Therefore, CYP2C19 transgenic mouse in potentially useful model of hyperkinetic disorders, and our findings hint at the possible impact of CYP2C19 enzyme on the development of the several brain regions involved in motor and emotional functioning.
PB  - Elsevier
C3  - European Neuropsychopharmacology
T1  - Reduced cerebellum volume and ataxia-like motoric phenotype in transgenic mouse, carrier of human CYP2C19 gene
VL  - 40
IS  - 1
SP  - S207
EP  - S208
DO  - 10.1016/j.euroneuro.2020.09.271
ER  - 

@conference{
author = "Milosavljević, Filip and Vučić, Marija and Manojlović, Marina and Miloševski, Teodora and Batinić, Bojan and Novalen, Maria and Miksys, Sharon and Tyndale, Rachel and Ingelman-Sundberg, Magnus and Pešić, Vesna and Jukić, Marin",
year = "2020",
abstract = "Introduction: CYP2C19 transgenic mouse (2C19TG) is generated by the insertion of 12 copies of the human CYP2C19 gene into mouse genome. This animal model is a tool to study the neurodevelopmental role of CYP2C19 in vivo, since this enzyme is expressed in the foetal brains of 2C19TG mice and humans. Previous studies [1,2] showed anxiety and depression-like behaviour in these mice, while the aim of this study was to characterize the motoric function of the 2C19TG mouse.
Methods: Whole brain dopamine concentration was measured in the brain homogenate of 23 adult mice by the HPLC-MS method. Motoric function in 50 mutant and 43 control mice of both genders was tested by the rotarod and beam walking tests. Beam walking test was repeated after treatment with dopaminergic receptor antagonists, Ecopipam (0.1 mg/kg) and Raclopride (0.25 mg/kg) as a follow-up. The sections of 10 6-month old and 8 15-months old mice were stained with anti-tyrosine hydroxylase antibody and the number of dopaminergic neurons was counted on histological slides under microscope. Next, after transcardial perfusion of 30 2C19TG and 30 control mice of both genders with contrast agent (4% Paraformaldehyde, 0.05M Gadoteridole, 0.01M Phosphate buffered saline, pH=7.4), cranium containing the whole brain was scanned overnight by the 9.4T MRI scanner. The volumes of 39 brain regions were quantified according to the mouse brain atlas [3]. Student's t-test and two-way ANOVA were used to evaluate statistical significance of between-group differences.
Results: Adult 2C19TG mice are hyperdopaminergic, as they exhibit 15% increased dopamine concentration (p<0.001). They also show hyperkinetic motoric phenotype with the ataxia-like walking pattern and pathological clasping reflex. In the beam walking test 2C19TG mice had 20% longer beam crossing time (p=0.007) and 60% more paw slips (p<0.001) then the controls, and this motoric impairment could not be improved with antidopaminergic drugs. Both younger and older 2C19TG mice exhibited only a marginal reduction in the number of dopaminergic neurons of both substantia nigra and ventral tegmental area in a subset of coronal sections. This was confirmed by the gadolinium-enhanced neuroimaging that showed no change in substantia nigra volume in 2C19TG mice. On the other hand, significant differences in volume were identified in 11 regions, including cerebellum (-8.3% p<0.001) and striatum (+3.0%, p<0.001), which are the regions connected with the motoric function. The volumetric changes were detected in the hippocampus (-1.3%, p=0.027), amygdala (+2.8%, p<0.001), septum (+3.3%, p=0.014) and nucleus accumbens (+3.5, p=0.004) of 2C19TG mice. These brain regions are involved in emotional and motivational functions.
Conclusion: Ataxia-like motoric phenotype in 2C19TG transgenic mice is probably caused by changes in cerebellum, while hyperdopaminergism is most likely the compensatory adaptation, whereas the changes in the hippocampus, amygdala, septum, and nucleus accumbens may be connected with the mutants’ depression-like phenotype and susceptibility to stress. Therefore, CYP2C19 transgenic mouse in potentially useful model of hyperkinetic disorders, and our findings hint at the possible impact of CYP2C19 enzyme on the development of the several brain regions involved in motor and emotional functioning.",
publisher = "Elsevier",
journal = "European Neuropsychopharmacology",
title = "Reduced cerebellum volume and ataxia-like motoric phenotype in transgenic mouse, carrier of human CYP2C19 gene",
volume = "40",
number = "1",
pages = "S207-S208",
doi = "10.1016/j.euroneuro.2020.09.271"
}

Milosavljević, F., Vučić, M., Manojlović, M., Miloševski, T., Batinić, B., Novalen, M., Miksys, S., Tyndale, R., Ingelman-Sundberg, M., Pešić, V.,& Jukić, M.. (2020). Reduced cerebellum volume and ataxia-like motoric phenotype in transgenic mouse, carrier of human CYP2C19 gene. in European Neuropsychopharmacology
Elsevier., 40(1), S207-S208.
https://doi.org/10.1016/j.euroneuro.2020.09.271

Milosavljević F, Vučić M, Manojlović M, Miloševski T, Batinić B, Novalen M, Miksys S, Tyndale R, Ingelman-Sundberg M, Pešić V, Jukić M. Reduced cerebellum volume and ataxia-like motoric phenotype in transgenic mouse, carrier of human CYP2C19 gene. in European Neuropsychopharmacology. 2020;40(1):S207-S208.
doi:10.1016/j.euroneuro.2020.09.271 .

Milosavljević, Filip, Vučić, Marija, Manojlović, Marina, Miloševski, Teodora, Batinić, Bojan, Novalen, Maria, Miksys, Sharon, Tyndale, Rachel, Ingelman-Sundberg, Magnus, Pešić, Vesna, Jukić, Marin, "Reduced cerebellum volume and ataxia-like motoric phenotype in transgenic mouse, carrier of human CYP2C19 gene" in European Neuropsychopharmacology, 40, no. 1 (2020):S207-S208,
https://doi.org/10.1016/j.euroneuro.2020.09.271 . .

TY  - CONF
AU  - Pešić, Vesna
AU  - Dobrosavljević, Ana
AU  - Stanić, Dušanka
AU  - Batinić, Bojan
AU  - Plećaš, Bosiljka
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3299
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Ketamine in a model of depression resistant to tricyclic antidepressants
VL  - 29
IS  - Supplement 1
SP  - S271
EP  - S271
DO  - 10.1016/j.euroneuro.2018.11.430
ER  - 

@conference{
author = "Pešić, Vesna and Dobrosavljević, Ana and Stanić, Dušanka and Batinić, Bojan and Plećaš, Bosiljka",
year = "2019",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Ketamine in a model of depression resistant to tricyclic antidepressants",
volume = "29",
number = "Supplement 1",
pages = "S271-S271",
doi = "10.1016/j.euroneuro.2018.11.430"
}

Pešić, V., Dobrosavljević, A., Stanić, D., Batinić, B.,& Plećaš, B.. (2019). Ketamine in a model of depression resistant to tricyclic antidepressants. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 29(Supplement 1), S271-S271.
https://doi.org/10.1016/j.euroneuro.2018.11.430

Pešić V, Dobrosavljević A, Stanić D, Batinić B, Plećaš B. Ketamine in a model of depression resistant to tricyclic antidepressants. in European Neuropsychopharmacology. 2019;29(Supplement 1):S271-S271.
doi:10.1016/j.euroneuro.2018.11.430 .

Pešić, Vesna, Dobrosavljević, Ana, Stanić, Dušanka, Batinić, Bojan, Plećaš, Bosiljka, "Ketamine in a model of depression resistant to tricyclic antidepressants" in European Neuropsychopharmacology, 29, no. Supplement 1 (2019):S271-S271,
https://doi.org/10.1016/j.euroneuro.2018.11.430 . .

TY  - CONF
AU  - Milosavljević, Filip
AU  - Vučić, M.
AU  - Manojlović, Marina
AU  - Ašujić, N.
AU  - Batinić, Bojan
AU  - Novalen, M.
AU  - Miksys, S.
AU  - Tyndale, R.F.
AU  - Ingelman-Sundberg, Magnus
AU  - Pešić, Vesna
AU  - Jukić, Marin
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3297
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Transgenic mouse, carrier of human CYP2C19 gene, as an animal model for hyperdopaminergism-induced hyperkinesia
VL  - 29
IS  - Supplement 2
SP  - S672
EP  - S673
DO  - 10.1016/j.euroneuro.2019.01.056
ER  - 

@conference{
author = "Milosavljević, Filip and Vučić, M. and Manojlović, Marina and Ašujić, N. and Batinić, Bojan and Novalen, M. and Miksys, S. and Tyndale, R.F. and Ingelman-Sundberg, Magnus and Pešić, Vesna and Jukić, Marin",
year = "2019",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Transgenic mouse, carrier of human CYP2C19 gene, as an animal model for hyperdopaminergism-induced hyperkinesia",
volume = "29",
number = "Supplement 2",
pages = "S672-S673",
doi = "10.1016/j.euroneuro.2019.01.056"
}

Milosavljević, F., Vučić, M., Manojlović, M., Ašujić, N., Batinić, B., Novalen, M., Miksys, S., Tyndale, R.F., Ingelman-Sundberg, M., Pešić, V.,& Jukić, M.. (2019). Transgenic mouse, carrier of human CYP2C19 gene, as an animal model for hyperdopaminergism-induced hyperkinesia. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 29(Supplement 2), S672-S673.
https://doi.org/10.1016/j.euroneuro.2019.01.056

Milosavljević F, Vučić M, Manojlović M, Ašujić N, Batinić B, Novalen M, Miksys S, Tyndale R, Ingelman-Sundberg M, Pešić V, Jukić M. Transgenic mouse, carrier of human CYP2C19 gene, as an animal model for hyperdopaminergism-induced hyperkinesia. in European Neuropsychopharmacology. 2019;29(Supplement 2):S672-S673.
doi:10.1016/j.euroneuro.2019.01.056 .

Milosavljević, Filip, Vučić, M., Manojlović, Marina, Ašujić, N., Batinić, Bojan, Novalen, M., Miksys, S., Tyndale, R.F., Ingelman-Sundberg, Magnus, Pešić, Vesna, Jukić, Marin, "Transgenic mouse, carrier of human CYP2C19 gene, as an animal model for hyperdopaminergism-induced hyperkinesia" in European Neuropsychopharmacology, 29, no. Supplement 2 (2019):S672-S673,
https://doi.org/10.1016/j.euroneuro.2019.01.056 . .

TY  - CONF
AU  - Stanković, Tamara
AU  - Batinić, Bojan
AU  - Savić, Miroslav
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3300
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - A novel positive modulator of alpha 4-GABAA receptors, XHe-III-74, reduces ethanol intake in mouse "drinking in the dark" model
VL  - 29
IS  - Supplement 1
SP  - S576
EP  - S577
DO  - 10.1016/j.euroneuro.2018.11.855
ER  - 

@conference{
author = "Stanković, Tamara and Batinić, Bojan and Savić, Miroslav",
year = "2019",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "A novel positive modulator of alpha 4-GABAA receptors, XHe-III-74, reduces ethanol intake in mouse "drinking in the dark" model",
volume = "29",
number = "Supplement 1",
pages = "S576-S577",
doi = "10.1016/j.euroneuro.2018.11.855"
}

Stanković, T., Batinić, B.,& Savić, M.. (2019). A novel positive modulator of alpha 4-GABAA receptors, XHe-III-74, reduces ethanol intake in mouse "drinking in the dark" model. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 29(Supplement 1), S576-S577.
https://doi.org/10.1016/j.euroneuro.2018.11.855

Stanković T, Batinić B, Savić M. A novel positive modulator of alpha 4-GABAA receptors, XHe-III-74, reduces ethanol intake in mouse "drinking in the dark" model. in European Neuropsychopharmacology. 2019;29(Supplement 1):S576-S577.
doi:10.1016/j.euroneuro.2018.11.855 .

Stanković, Tamara, Batinić, Bojan, Savić, Miroslav, "A novel positive modulator of alpha 4-GABAA receptors, XHe-III-74, reduces ethanol intake in mouse "drinking in the dark" model" in European Neuropsychopharmacology, 29, no. Supplement 1 (2019):S576-S577,
https://doi.org/10.1016/j.euroneuro.2018.11.855 . .

TY  - JOUR
AU  - Batinić, Bojan
AU  - Stanković, Tamara
AU  - Stephen, Michael
AU  - Kodali, Revathi
AU  - Tiruveedhula, Veera V.
AU  - Li, Guanguan
AU  - Scholze, Petra
AU  - Marković, Bojan
AU  - Obradović, Aleksandar
AU  - Ernst, Margot
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3070
AB  - It is unclear whether GABA(A) receptors (GABA(A)Rs) that contain the alpha 3-subunit are substantially involved in the anxiolytic effects of benzodiazepines (BDZs). In the present study, we tested YT-III-31, a newer BDZ ligand with functional preference for alpha 3 ss gamma 2 GABA(A) Rs, in two paradigms of unconditioned anxiety, the open field and elevated plus maze in rats. The effective dose of YT-III-31 (2 mg/kg) displayed a clear anxiolytic-like profile, unhampered by sedative action, in both tests. At a higher dose (10 mg/kg), YT-III-31 induced ataxia in the rotarod and sedation in spontaneous locomotor activity test. The latter effect was preventable by flumazenil and ss CCt, the non-selective and alpha 1 ss gamma 2 GABA(A)R affinity-selective antagonist, respectively, demonstrating that sedative properties of YT-III-31, when attained, are mediated by the alpha 1 gamma 2 site. To elucidate the receptor substrate of subtle behavioral differences between YT-III-31 and diazepam, we approximated in vivo receptor potentiation for both ligands, based on estimated unbound concentrations in rat brains. Far different from diazepam, YT-III-31 has significantly lower affinity for the alpha 1 gamma 2 over other BDZ-sensitive sites, and at lower doses (1-2 mg/kg) was devoid of potentiation at alpha 1 ss gamma 2 GABA(A)Rs. The approximation approach revealed a modest selectivity of YT-III-31 for alpha 3 gamma 2- in comparison to alpha 2 gamma 2 and alpha 5 gamma 2 binding sites, suggesting that its anxiolytic-like activity may not necessarily or predominantly reflect potentiation at alpha 3 ss gamma 2 GABA(A)Rs. Nonetheless, as the anxiolytic effects are achievable at a dose devoid of any sedative potential, and having favorable safety (cytotoxicity) and metabolic stability profile, YT-III-31 represents a valuable candidate for further translational research.
PB  - Elsevier Science BV, Amsterdam
T2  - European Neuropsychopharmacology
T1  - Attaining in vivo selectivity of positive modulation of alpha 3 ss gamma 2 GABA(A) receptors in rats: A hard task!
VL  - 28
IS  - 8
SP  - 903
EP  - 914
DO  - 10.1016/j.euroneuro.2018.05.014
ER  - 

@article{
author = "Batinić, Bojan and Stanković, Tamara and Stephen, Michael and Kodali, Revathi and Tiruveedhula, Veera V. and Li, Guanguan and Scholze, Petra and Marković, Bojan and Obradović, Aleksandar and Ernst, Margot and Cook, James M. and Savić, Miroslav",
year = "2018",
abstract = "It is unclear whether GABA(A) receptors (GABA(A)Rs) that contain the alpha 3-subunit are substantially involved in the anxiolytic effects of benzodiazepines (BDZs). In the present study, we tested YT-III-31, a newer BDZ ligand with functional preference for alpha 3 ss gamma 2 GABA(A) Rs, in two paradigms of unconditioned anxiety, the open field and elevated plus maze in rats. The effective dose of YT-III-31 (2 mg/kg) displayed a clear anxiolytic-like profile, unhampered by sedative action, in both tests. At a higher dose (10 mg/kg), YT-III-31 induced ataxia in the rotarod and sedation in spontaneous locomotor activity test. The latter effect was preventable by flumazenil and ss CCt, the non-selective and alpha 1 ss gamma 2 GABA(A)R affinity-selective antagonist, respectively, demonstrating that sedative properties of YT-III-31, when attained, are mediated by the alpha 1 gamma 2 site. To elucidate the receptor substrate of subtle behavioral differences between YT-III-31 and diazepam, we approximated in vivo receptor potentiation for both ligands, based on estimated unbound concentrations in rat brains. Far different from diazepam, YT-III-31 has significantly lower affinity for the alpha 1 gamma 2 over other BDZ-sensitive sites, and at lower doses (1-2 mg/kg) was devoid of potentiation at alpha 1 ss gamma 2 GABA(A)Rs. The approximation approach revealed a modest selectivity of YT-III-31 for alpha 3 gamma 2- in comparison to alpha 2 gamma 2 and alpha 5 gamma 2 binding sites, suggesting that its anxiolytic-like activity may not necessarily or predominantly reflect potentiation at alpha 3 ss gamma 2 GABA(A)Rs. Nonetheless, as the anxiolytic effects are achievable at a dose devoid of any sedative potential, and having favorable safety (cytotoxicity) and metabolic stability profile, YT-III-31 represents a valuable candidate for further translational research.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Attaining in vivo selectivity of positive modulation of alpha 3 ss gamma 2 GABA(A) receptors in rats: A hard task!",
volume = "28",
number = "8",
pages = "903-914",
doi = "10.1016/j.euroneuro.2018.05.014"
}

Batinić, B., Stanković, T., Stephen, M., Kodali, R., Tiruveedhula, V. V., Li, G., Scholze, P., Marković, B., Obradović, A., Ernst, M., Cook, J. M.,& Savić, M.. (2018). Attaining in vivo selectivity of positive modulation of alpha 3 ss gamma 2 GABA(A) receptors in rats: A hard task!. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 28(8), 903-914.
https://doi.org/10.1016/j.euroneuro.2018.05.014

Batinić B, Stanković T, Stephen M, Kodali R, Tiruveedhula VV, Li G, Scholze P, Marković B, Obradović A, Ernst M, Cook JM, Savić M. Attaining in vivo selectivity of positive modulation of alpha 3 ss gamma 2 GABA(A) receptors in rats: A hard task!. in European Neuropsychopharmacology. 2018;28(8):903-914.
doi:10.1016/j.euroneuro.2018.05.014 .

Batinić, Bojan, Stanković, Tamara, Stephen, Michael, Kodali, Revathi, Tiruveedhula, Veera V., Li, Guanguan, Scholze, Petra, Marković, Bojan, Obradović, Aleksandar, Ernst, Margot, Cook, James M., Savić, Miroslav, "Attaining in vivo selectivity of positive modulation of alpha 3 ss gamma 2 GABA(A) receptors in rats: A hard task!" in European Neuropsychopharmacology, 28, no. 8 (2018):903-914,
https://doi.org/10.1016/j.euroneuro.2018.05.014 . .

TY  - JOUR
AU  - Ilić, Tanja
AU  - Savić, Sanela
AU  - Batinić, Bojan
AU  - Marković, Bojan
AU  - Schmidberger, Markus
AU  - Lunter, Dominique
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3047
AB  - This study aimed to investigate the potential of lecithin-based nanoemulsions costabilized by sucrose esters, with and without skin pretreatment with stainless steel microneedles, to improve delivery of aceclofenac, as a model drug, into/across the skin. The characterization revealed favorable droplet size (about 180 nm), narrow size distribution (  lt  0.15), high surface charge (about - 40 mV) and satisfying long-term stability (one year at 4 +/- 1 degrees C) of the formulation costabilized by sucrose palmitate, demonstrating a similar trend observed for the reference stabilized by widely used lecithin/polysorbate 80 combination. In vitro release/permeation testing and differential stripping on the porcine ear proved the superiority of the sucrose ester- over polysorbate-based nanoemulsion. However, in vitro findings were not fully indicative of the in vivo performances - no significant differences were observed between investigated formulations in pharmacokinetic profile and total amount of aceclofenac deposited in the rat skin 24 h after dosing, simultaneously pointing to delayed aceclofenac delivery into the systemic circulation. In addition, the ratio of plasma concentrations of aceclofenac and its major metabolite in rats, diclofenac, was remarkably changed after topical application of tested nanoemulsions compared to intravenous administration of aceclofenac solution. Finally, skin pretreatment with microneedles improved aceclofenac delivery into/across the rat skin from tested formulations, resulting in 1.4-2.1-fold increased bioavailability and 1.2-1.7-fold enhanced level of aceclofenac retained in the skin, as measured 24 h after administration. Moreover, the plasma concentrations of aceclofenac 24 h after application of tested formulations (lecithin/sucrose palmitate vs. lecithin/polysorbate 80) combined with microneedles (173.37 +/- 40.50 ng/ml vs. 259.23 +/- 73.18 ng/ml) were significantly higher than those obtained through intact skin (105.69 +/- 19.53 ng/ml vs. 88.38 +/- 14.46 ng/ml). However, obtained results suggest that combination of microneedles and sucrose palmitate-costabilized nanoemulsion could be useful to attain higher skin concentration, while combination of microneedles with polysorbate 80-costabilized nanoemulsion could be a preferable option for enhancing drug delivery into the bloodstream.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies
VL  - 125
SP  - 110
EP  - 119
DO  - 10.1016/j.ejps.2018.09.023
ER  - 

@article{
author = "Ilić, Tanja and Savić, Sanela and Batinić, Bojan and Marković, Bojan and Schmidberger, Markus and Lunter, Dominique and Savić, Miroslav and Savić, Snežana",
year = "2018",
abstract = "This study aimed to investigate the potential of lecithin-based nanoemulsions costabilized by sucrose esters, with and without skin pretreatment with stainless steel microneedles, to improve delivery of aceclofenac, as a model drug, into/across the skin. The characterization revealed favorable droplet size (about 180 nm), narrow size distribution (  lt  0.15), high surface charge (about - 40 mV) and satisfying long-term stability (one year at 4 +/- 1 degrees C) of the formulation costabilized by sucrose palmitate, demonstrating a similar trend observed for the reference stabilized by widely used lecithin/polysorbate 80 combination. In vitro release/permeation testing and differential stripping on the porcine ear proved the superiority of the sucrose ester- over polysorbate-based nanoemulsion. However, in vitro findings were not fully indicative of the in vivo performances - no significant differences were observed between investigated formulations in pharmacokinetic profile and total amount of aceclofenac deposited in the rat skin 24 h after dosing, simultaneously pointing to delayed aceclofenac delivery into the systemic circulation. In addition, the ratio of plasma concentrations of aceclofenac and its major metabolite in rats, diclofenac, was remarkably changed after topical application of tested nanoemulsions compared to intravenous administration of aceclofenac solution. Finally, skin pretreatment with microneedles improved aceclofenac delivery into/across the rat skin from tested formulations, resulting in 1.4-2.1-fold increased bioavailability and 1.2-1.7-fold enhanced level of aceclofenac retained in the skin, as measured 24 h after administration. Moreover, the plasma concentrations of aceclofenac 24 h after application of tested formulations (lecithin/sucrose palmitate vs. lecithin/polysorbate 80) combined with microneedles (173.37 +/- 40.50 ng/ml vs. 259.23 +/- 73.18 ng/ml) were significantly higher than those obtained through intact skin (105.69 +/- 19.53 ng/ml vs. 88.38 +/- 14.46 ng/ml). However, obtained results suggest that combination of microneedles and sucrose palmitate-costabilized nanoemulsion could be useful to attain higher skin concentration, while combination of microneedles with polysorbate 80-costabilized nanoemulsion could be a preferable option for enhancing drug delivery into the bloodstream.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies",
volume = "125",
pages = "110-119",
doi = "10.1016/j.ejps.2018.09.023"
}

Ilić, T., Savić, S., Batinić, B., Marković, B., Schmidberger, M., Lunter, D., Savić, M.,& Savić, S.. (2018). Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 125, 110-119.
https://doi.org/10.1016/j.ejps.2018.09.023

Ilić T, Savić S, Batinić B, Marković B, Schmidberger M, Lunter D, Savić M, Savić S. Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies. in European Journal of Pharmaceutical Sciences. 2018;125:110-119.
doi:10.1016/j.ejps.2018.09.023 .

Ilić, Tanja, Savić, Sanela, Batinić, Bojan, Marković, Bojan, Schmidberger, Markus, Lunter, Dominique, Savić, Miroslav, Savić, Snežana, "Combined use of biocompatible nanoemulsions and solid microneedles to improve transport of a model NSAID across the skin: In vitro and in vivo studies" in European Journal of Pharmaceutical Sciences, 125 (2018):110-119,
https://doi.org/10.1016/j.ejps.2018.09.023 . .

TY  - CONF
AU  - Stanković, Tamara
AU  - Batinić, Bojan
AU  - Santrač, Anja
AU  - Marković, Bojan
AU  - Drobac, Milica
AU  - Arsenijević, Jelena
AU  - Savić, Miroslav
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5284
AB  - Cilj ove studije bio je da se ispita da li akutni tretman ligandom XHe‐III‐74, novim
pozitivnim modulatorom α4‐GABAA receptora, može smanjiti unos alkohola u mišijem
modelu „pijenja u mraku” (eng. drinking in the dark – DID).
Eksperimenti su sprovedeni na odraslim miševima soja C57BL/6. Moguće
sedativno dejstvo XHe‐III‐74 (0,5; 2 ili 5 mg/kg, i.p.) ispitano je u testu spontane
lokomotorne aktivnosti (SLA). Prvog dana jednog ciklusa DID eksperimenta svaka
životinja imala je dvočasovni pristup alkoholu (etanol 20%, v/v). Drugog dana tretman
je primenjivan 20 minuta pre pristupa alkoholu, a trećeg dana pacovi nisu tretirani
ničim. U svim DID eksperimentima svaka životinja je prošla kroz četiri ciklusa tako da je
u svakom primila jednu od tri doze tretmana ili placebo. U prvom DID eksperimentu
testirali smo efekat XHe‐III‐74 (0,8; 2 ili 5 mg/kg) na unos vode (n=12, po dozi), dok
smo u drugom testirali efekat istih doza na unos alkohola (n=14). Ekekat referetnog
leka, naltreksona (1; 4 ili 16 mg/kg) testiran je u trećem eksperimentu.
U SLA testu, nijedna od odabranih doza XHe‐III‐74 nije smanjila pređeni put životinje
(F3,20=0,48; p=0,703). U prvom DID eksperiementu, tretman XHe‐III‐74 nije uticao na
unos vode (F3,33=0,39; p=0,763). Unos alkohola, meren u drugom DID eksperimentu,
izmenjen je pod dejstvom XHe‐III‐74 tretmana (F3,39=7,41; p<0,001), gde je doza XHe‐
III‐74 od 5 mg/kg značajno smanjila unos u poređenju sa kontrolom (p<0,001). U
trećem eksperimentu, naltrekson je značajno smanjio unos alkohola (F60,3=22.18;
p<0,001), i to u sve tri doze: 1 mg/kg (p<0,001); 4 mg/kg (p<0,001) i 16 mg/kg
(p<0,001).
Uz očekivani izostanak sedativnog dejstva, XHe‐III‐74, pozitivni modulator α4‐
GABAA receptora, ispoljio je evidentan potencijal za smanjenje unosa alkohola u
mišijem DID modelu, koji se može porediti sa onim postignutim primenom naltreksona,
referentnog leka u terapiji poremećaja unosa alkohola.
AB  - The present study aimed to investigate whether acute treatment with XHe‐III‐74,
a novel positive modulator of α4‐GABAA receptors, may reduce alcohol intake in mouse
model of „drinking in the dark” (DID).
All experiments were conducted on adult C57BL/6 mice. Potential sedative
properties of XHe‐III‐74, (0.5, 2 or 5 mg/kg, i.p.) were assessed using spontaneous
locomotor activity (SLA) test. On the 1st day of one DID cycle each animal had 2‐h access
to ethanol (20%, v/v), on the 2nd day treatment was given 20 min before the access to
ethanol, while on the 3rd day the animal was not treated in any way. In all DID
experiments each animal passed through four cycles and respectively receive one of
three treatment doses or solvent in each cycle. In Experiment 1 we tested whether XHe‐
III‐74 (0.8, 2 or 5 mg/kg) had any effects on water intake (n=12 per treatment dose),
while in Experiment 2, the same doses were used to test potential decrease of ethanol
intake (n=14). Effects of the reference drug, naltrexone (1; 4 and 16 mg/kg) were
tested in Experiment 3 (n=21). In the SLA test, none of the selected XHe‐III‐74 doses
decreased the distance traveled (F3,20=0.48; p=0.703). In DID Experiment 1, XHe‐III‐74
treatment didn’t affect water intake (F33,3=0.39; p=0.763). Ethanol intake, measured in
Experiment 2, was affected by XHe‐III‐74 treatment (F39,3=7.41; p<0.001), with 5 mg/kg
XHe‐III‐74 significantly reducing the intake relative to control (p<0.001). In Experiment
3, naltrexone significantly affected the intake of ethanol (F60,3=22.18; p<0.001), with all
three doses reducing the intake: 1 mg/kg (p<0.001); 4 mg/kg (p<0.001) and 16 mg/kg
(p<0.001).
With expected lack of sedative actions, XHe‐III‐74, a positive modulator of α4‐
GABAARs, exhibited a clear potential for decreasing ethanol intake in mouse DID model,
comparable to that of naltrexone, a reference drug in alcohol use disorder.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Novi pozitivni modulator α4-GABAA receptora, XHE-III-74, smanjuje unos alkohola u mišijem modelu "pijenja u mraku"
T1  - A novel positive modulator of α4‐GABAA receptors, XHE-III‐74, reduces ethanol intake in mouse „drinking in the dark” model
VL  - 68
IS  - 3
SP  - 664
EP  - 665
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5284
ER  - 

@conference{
author = "Stanković, Tamara and Batinić, Bojan and Santrač, Anja and Marković, Bojan and Drobac, Milica and Arsenijević, Jelena and Savić, Miroslav",
year = "2018",
abstract = "Cilj ove studije bio je da se ispita da li akutni tretman ligandom XHe‐III‐74, novim
pozitivnim modulatorom α4‐GABAA receptora, može smanjiti unos alkohola u mišijem
modelu „pijenja u mraku” (eng. drinking in the dark – DID).
Eksperimenti su sprovedeni na odraslim miševima soja C57BL/6. Moguće
sedativno dejstvo XHe‐III‐74 (0,5; 2 ili 5 mg/kg, i.p.) ispitano je u testu spontane
lokomotorne aktivnosti (SLA). Prvog dana jednog ciklusa DID eksperimenta svaka
životinja imala je dvočasovni pristup alkoholu (etanol 20%, v/v). Drugog dana tretman
je primenjivan 20 minuta pre pristupa alkoholu, a trećeg dana pacovi nisu tretirani
ničim. U svim DID eksperimentima svaka životinja je prošla kroz četiri ciklusa tako da je
u svakom primila jednu od tri doze tretmana ili placebo. U prvom DID eksperimentu
testirali smo efekat XHe‐III‐74 (0,8; 2 ili 5 mg/kg) na unos vode (n=12, po dozi), dok
smo u drugom testirali efekat istih doza na unos alkohola (n=14). Ekekat referetnog
leka, naltreksona (1; 4 ili 16 mg/kg) testiran je u trećem eksperimentu.
U SLA testu, nijedna od odabranih doza XHe‐III‐74 nije smanjila pređeni put životinje
(F3,20=0,48; p=0,703). U prvom DID eksperiementu, tretman XHe‐III‐74 nije uticao na
unos vode (F3,33=0,39; p=0,763). Unos alkohola, meren u drugom DID eksperimentu,
izmenjen je pod dejstvom XHe‐III‐74 tretmana (F3,39=7,41; p<0,001), gde je doza XHe‐
III‐74 od 5 mg/kg značajno smanjila unos u poređenju sa kontrolom (p<0,001). U
trećem eksperimentu, naltrekson je značajno smanjio unos alkohola (F60,3=22.18;
p<0,001), i to u sve tri doze: 1 mg/kg (p<0,001); 4 mg/kg (p<0,001) i 16 mg/kg
(p<0,001).
Uz očekivani izostanak sedativnog dejstva, XHe‐III‐74, pozitivni modulator α4‐
GABAA receptora, ispoljio je evidentan potencijal za smanjenje unosa alkohola u
mišijem DID modelu, koji se može porediti sa onim postignutim primenom naltreksona,
referentnog leka u terapiji poremećaja unosa alkohola., The present study aimed to investigate whether acute treatment with XHe‐III‐74,
a novel positive modulator of α4‐GABAA receptors, may reduce alcohol intake in mouse
model of „drinking in the dark” (DID).
All experiments were conducted on adult C57BL/6 mice. Potential sedative
properties of XHe‐III‐74, (0.5, 2 or 5 mg/kg, i.p.) were assessed using spontaneous
locomotor activity (SLA) test. On the 1st day of one DID cycle each animal had 2‐h access
to ethanol (20%, v/v), on the 2nd day treatment was given 20 min before the access to
ethanol, while on the 3rd day the animal was not treated in any way. In all DID
experiments each animal passed through four cycles and respectively receive one of
three treatment doses or solvent in each cycle. In Experiment 1 we tested whether XHe‐
III‐74 (0.8, 2 or 5 mg/kg) had any effects on water intake (n=12 per treatment dose),
while in Experiment 2, the same doses were used to test potential decrease of ethanol
intake (n=14). Effects of the reference drug, naltrexone (1; 4 and 16 mg/kg) were
tested in Experiment 3 (n=21). In the SLA test, none of the selected XHe‐III‐74 doses
decreased the distance traveled (F3,20=0.48; p=0.703). In DID Experiment 1, XHe‐III‐74
treatment didn’t affect water intake (F33,3=0.39; p=0.763). Ethanol intake, measured in
Experiment 2, was affected by XHe‐III‐74 treatment (F39,3=7.41; p<0.001), with 5 mg/kg
XHe‐III‐74 significantly reducing the intake relative to control (p<0.001). In Experiment
3, naltrexone significantly affected the intake of ethanol (F60,3=22.18; p<0.001), with all
three doses reducing the intake: 1 mg/kg (p<0.001); 4 mg/kg (p<0.001) and 16 mg/kg
(p<0.001).
With expected lack of sedative actions, XHe‐III‐74, a positive modulator of α4‐
GABAARs, exhibited a clear potential for decreasing ethanol intake in mouse DID model,
comparable to that of naltrexone, a reference drug in alcohol use disorder.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Novi pozitivni modulator α4-GABAA receptora, XHE-III-74, smanjuje unos alkohola u mišijem modelu "pijenja u mraku", A novel positive modulator of α4‐GABAA receptors, XHE-III‐74, reduces ethanol intake in mouse „drinking in the dark” model",
volume = "68",
number = "3",
pages = "664-665",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5284"
}

Stanković, T., Batinić, B., Santrač, A., Marković, B., Drobac, M., Arsenijević, J.,& Savić, M.. (2018). Novi pozitivni modulator α4-GABAA receptora, XHE-III-74, smanjuje unos alkohola u mišijem modelu "pijenja u mraku". in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 68(3), 664-665.
https://hdl.handle.net/21.15107/rcub_farfar_5284

Stanković T, Batinić B, Santrač A, Marković B, Drobac M, Arsenijević J, Savić M. Novi pozitivni modulator α4-GABAA receptora, XHE-III-74, smanjuje unos alkohola u mišijem modelu "pijenja u mraku". in Arhiv za farmaciju. 2018;68(3):664-665.
https://hdl.handle.net/21.15107/rcub_farfar_5284 .

Stanković, Tamara, Batinić, Bojan, Santrač, Anja, Marković, Bojan, Drobac, Milica, Arsenijević, Jelena, Savić, Miroslav, "Novi pozitivni modulator α4-GABAA receptora, XHE-III-74, smanjuje unos alkohola u mišijem modelu "pijenja u mraku"" in Arhiv za farmaciju, 68, no. 3 (2018):664-665,
https://hdl.handle.net/21.15107/rcub_farfar_5284 .

TY  - JOUR
AU  - Durić, Vedrana
AU  - Batinić, Bojan
AU  - Petrović, Jelena
AU  - Stanić, Dušanka
AU  - Bulat, Zorica
AU  - Pešić, Vesna
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3172
AB  - Although a magnesium-mediated attenuation of memory deficits was reported in animal models of ageing and traumatic brain injury, a possible memory enhancement in healthy subjects has not been investigated yet. We used novel object recognition test (NORT) to examine the effects of acute (30 mg/kg) and chronic (50 mg/kg, 28 days) Mg-sulfate treatment on the long-term memory (LTM) in healthy adult male rats, and to test the sustainability of magnesium effects in the models of acute and chronic (21 days) ACTH administration (10 mu g/animal), mimicking the stress- and depression-like conditions. A single dose of Mg-sulfate enhanced the LTM retrieval in the 24 h inter-trial NORT protocol, in healthy, as well as in rats acutely treated with ACTH. Memory enhancement was also detected after 4-week long Mg-sulfate intake, in both healthy and rats chronically treated with ACTH. While the present findings on procognitive effects of chronic Mg-sulfate treatment corroborate with those from studies on the therapeutic potential of Mg-threonate, the current study is the first to report on memory enhancement induced by a single dose of magnesium.
PB  - John Libbey Eurotext Ltd, Montrouge
T2  - Magnesium Research
T1  - A single dose of magnesium, as well as chronic administration, enhances long-term memory in novel object recognition test, in healthy and ACTH-treated rats
VL  - 31
IS  - 1
SP  - 24
EP  - 32
DO  - 10.1684/mrh.2018.0435
ER  - 

@article{
author = "Durić, Vedrana and Batinić, Bojan and Petrović, Jelena and Stanić, Dušanka and Bulat, Zorica and Pešić, Vesna",
year = "2018",
abstract = "Although a magnesium-mediated attenuation of memory deficits was reported in animal models of ageing and traumatic brain injury, a possible memory enhancement in healthy subjects has not been investigated yet. We used novel object recognition test (NORT) to examine the effects of acute (30 mg/kg) and chronic (50 mg/kg, 28 days) Mg-sulfate treatment on the long-term memory (LTM) in healthy adult male rats, and to test the sustainability of magnesium effects in the models of acute and chronic (21 days) ACTH administration (10 mu g/animal), mimicking the stress- and depression-like conditions. A single dose of Mg-sulfate enhanced the LTM retrieval in the 24 h inter-trial NORT protocol, in healthy, as well as in rats acutely treated with ACTH. Memory enhancement was also detected after 4-week long Mg-sulfate intake, in both healthy and rats chronically treated with ACTH. While the present findings on procognitive effects of chronic Mg-sulfate treatment corroborate with those from studies on the therapeutic potential of Mg-threonate, the current study is the first to report on memory enhancement induced by a single dose of magnesium.",
publisher = "John Libbey Eurotext Ltd, Montrouge",
journal = "Magnesium Research",
title = "A single dose of magnesium, as well as chronic administration, enhances long-term memory in novel object recognition test, in healthy and ACTH-treated rats",
volume = "31",
number = "1",
pages = "24-32",
doi = "10.1684/mrh.2018.0435"
}

Durić, V., Batinić, B., Petrović, J., Stanić, D., Bulat, Z.,& Pešić, V.. (2018). A single dose of magnesium, as well as chronic administration, enhances long-term memory in novel object recognition test, in healthy and ACTH-treated rats. in Magnesium Research
John Libbey Eurotext Ltd, Montrouge., 31(1), 24-32.
https://doi.org/10.1684/mrh.2018.0435

Durić V, Batinić B, Petrović J, Stanić D, Bulat Z, Pešić V. A single dose of magnesium, as well as chronic administration, enhances long-term memory in novel object recognition test, in healthy and ACTH-treated rats. in Magnesium Research. 2018;31(1):24-32.
doi:10.1684/mrh.2018.0435 .

Durić, Vedrana, Batinić, Bojan, Petrović, Jelena, Stanić, Dušanka, Bulat, Zorica, Pešić, Vesna, "A single dose of magnesium, as well as chronic administration, enhances long-term memory in novel object recognition test, in healthy and ACTH-treated rats" in Magnesium Research, 31, no. 1 (2018):24-32,
https://doi.org/10.1684/mrh.2018.0435 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Stanić, Dušanka
AU  - Bulat, Zorica
AU  - Puskas, Nela
AU  - Labudović-Borović, Milica
AU  - Batinić, Bojan
AU  - Mirković, Duško
AU  - Ignjatović, Svetlana
AU  - Pešić, Vesna
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3042
AB  - Magnesium (Mg), is not only a modulator of the glutamatergic NMDA receptors' affinity, it also prevents HPA axis hyperactivity, thus possibly being implicated in neurobiological features of mood disorders. Further uncovering of molecular mechanisms underlying magnesium's proposed effects is needed due to the recent shift in research of treatment resistant depression (TRD) towards glutamatergic pathways. Here, we applied Mg via drinking water for 28 days (50 mg/kg/day), in ACTH-treated rats, an established animal model of depression resistant to tricyclic antidepressants. Using this model in male rats we measured (1) changes in hippocampal neurogenesis and behavioral alterations, (2) adrenal hormones response to acute stress challenge and (3) levels of biometals involved in regulation of monoamines turnover in rat prefrontal cortex. Our results support beneficial behavioral impact of Mg in TRD model together with increased hippocampal neurogenesis and BDNF expression. Furthermore, Mg prevented ACTH-induced disruption in HPA axis function, by normalizing the levels of plasma ACTH, corticosterone and interleukin-6, and by increasing the peripheral release of adrenaline, noradrenaline and serotonin after the acute stress challenge. Finally, the influence on copper/zinc ratio suggested probable magnesium's involvement in monoamine turnover in PFC. Our findings provide further insights into the possible pathways implicated in the behavioral modulation effects of Mg, as well as its central and peripheral effects in ACTH-induced TRD model. Thus, further investigation of molecular signaling related to the glutamatergic transmission and role of Mg, could reveal prospects to novel treatment strategies that could be of particular importance for patients suffering from TRD.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Hormones and Behavior
T1  - Acth-induced model of depression resistant to tricyclic antidepressants: Neuroendocrine and behavioral changes and influence of long-term magnesium administration
VL  - 105
SP  - 1
EP  - 10
DO  - 10.1016/j.yhbeh.2018.07.003
ER  - 

@article{
author = "Petrović, Jelena and Stanić, Dušanka and Bulat, Zorica and Puskas, Nela and Labudović-Borović, Milica and Batinić, Bojan and Mirković, Duško and Ignjatović, Svetlana and Pešić, Vesna",
year = "2018",
abstract = "Magnesium (Mg), is not only a modulator of the glutamatergic NMDA receptors' affinity, it also prevents HPA axis hyperactivity, thus possibly being implicated in neurobiological features of mood disorders. Further uncovering of molecular mechanisms underlying magnesium's proposed effects is needed due to the recent shift in research of treatment resistant depression (TRD) towards glutamatergic pathways. Here, we applied Mg via drinking water for 28 days (50 mg/kg/day), in ACTH-treated rats, an established animal model of depression resistant to tricyclic antidepressants. Using this model in male rats we measured (1) changes in hippocampal neurogenesis and behavioral alterations, (2) adrenal hormones response to acute stress challenge and (3) levels of biometals involved in regulation of monoamines turnover in rat prefrontal cortex. Our results support beneficial behavioral impact of Mg in TRD model together with increased hippocampal neurogenesis and BDNF expression. Furthermore, Mg prevented ACTH-induced disruption in HPA axis function, by normalizing the levels of plasma ACTH, corticosterone and interleukin-6, and by increasing the peripheral release of adrenaline, noradrenaline and serotonin after the acute stress challenge. Finally, the influence on copper/zinc ratio suggested probable magnesium's involvement in monoamine turnover in PFC. Our findings provide further insights into the possible pathways implicated in the behavioral modulation effects of Mg, as well as its central and peripheral effects in ACTH-induced TRD model. Thus, further investigation of molecular signaling related to the glutamatergic transmission and role of Mg, could reveal prospects to novel treatment strategies that could be of particular importance for patients suffering from TRD.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Hormones and Behavior",
title = "Acth-induced model of depression resistant to tricyclic antidepressants: Neuroendocrine and behavioral changes and influence of long-term magnesium administration",
volume = "105",
pages = "1-10",
doi = "10.1016/j.yhbeh.2018.07.003"
}

Petrović, J., Stanić, D., Bulat, Z., Puskas, N., Labudović-Borović, M., Batinić, B., Mirković, D., Ignjatović, S.,& Pešić, V.. (2018). Acth-induced model of depression resistant to tricyclic antidepressants: Neuroendocrine and behavioral changes and influence of long-term magnesium administration. in Hormones and Behavior
Academic Press Inc Elsevier Science, San Diego., 105, 1-10.
https://doi.org/10.1016/j.yhbeh.2018.07.003

Petrović J, Stanić D, Bulat Z, Puskas N, Labudović-Borović M, Batinić B, Mirković D, Ignjatović S, Pešić V. Acth-induced model of depression resistant to tricyclic antidepressants: Neuroendocrine and behavioral changes and influence of long-term magnesium administration. in Hormones and Behavior. 2018;105:1-10.
doi:10.1016/j.yhbeh.2018.07.003 .

Petrović, Jelena, Stanić, Dušanka, Bulat, Zorica, Puskas, Nela, Labudović-Borović, Milica, Batinić, Bojan, Mirković, Duško, Ignjatović, Svetlana, Pešić, Vesna, "Acth-induced model of depression resistant to tricyclic antidepressants: Neuroendocrine and behavioral changes and influence of long-term magnesium administration" in Hormones and Behavior, 105 (2018):1-10,
https://doi.org/10.1016/j.yhbeh.2018.07.003 . .

TY  - JOUR
AU  - Batinić, Bojan
AU  - Santrač, Anja
AU  - Jančić, Ivan
AU  - Li, Guanguan
AU  - Vidojević, Aleksandra
AU  - Marković, Bojan
AU  - Cook, James M.
AU  - Savić, Miroslav
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2821
AB  - We previously demonstrated that lipopolysaccharide (LPS) administered intraperitoneally (i.p.) to pregnant Wistar rat dams, at embryonic days 15 and 16 (E15/16), induced a decrease of baseline locomotor activity and diminished reactivity to amphetamine in adult female offspring. In the present study we aimed to assess the duration of LPS-induced maternal immune activation (MIA) and investigate possible changes in levels of main neurotransmitters in fetal brain during MIA. We hypothesized that the observed behavioral changes may be linked with MIA-induced disturbance of prenatal GABAergic system development, especially with alpha 5 GABA(A) receptors (alpha 5GABA(A)Rs), expression of which takes place between E14 and E17. Thereafter, we set to investigate if later potentiation of alpha 5GABA(A)Rs in offspring's preadolescence (from postnatal day 22-28) could prevent the deficit in locomotor reactivity to amphetamine observed in adulthood, at postnatal day P60. The elevation of IL-6 in amniotic fluid 6 h after LPS treatment (100 mu g/kg, i.p.) at E15 was concurrent with a significant increase of GABA and decrease of glutamate concentration in fetal brain. Moreover, repeated administration of MP-III-022, a selective positive allosteric modulator of alpha 5GABA(A)Rs, at a dose (2 mg/kg daily, i.p.) derived from a separate pharmacokinetic study, prevented the LPS-induced decrease in locomotor reactivity to amphetamine (0.5 mg/kg, i.p.) in adult females. These results were not mirrored in the parallel set of experiments with male offspring from LPS-treated rats. The results suggest that pharmacological potentiation of alpha 5GABA(A)Rs activity in preadolescence may ameliorate at least some of adverse consequences of exposure to MIA in utero.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - International Journal of Developmental Neuroscience
T1  - Positive modulation of alpha 5 GABA(A) receptors in preadolescence prevents reduced locomotor response to amphetamine in adult female but not male rats prenatally exposed to lipopolysaccharide
VL  - 61
SP  - 31
EP  - 39
DO  - 10.1016/j.ijdevneu.2017.06.001
ER  - 

@article{
author = "Batinić, Bojan and Santrač, Anja and Jančić, Ivan and Li, Guanguan and Vidojević, Aleksandra and Marković, Bojan and Cook, James M. and Savić, Miroslav",
year = "2017",
abstract = "We previously demonstrated that lipopolysaccharide (LPS) administered intraperitoneally (i.p.) to pregnant Wistar rat dams, at embryonic days 15 and 16 (E15/16), induced a decrease of baseline locomotor activity and diminished reactivity to amphetamine in adult female offspring. In the present study we aimed to assess the duration of LPS-induced maternal immune activation (MIA) and investigate possible changes in levels of main neurotransmitters in fetal brain during MIA. We hypothesized that the observed behavioral changes may be linked with MIA-induced disturbance of prenatal GABAergic system development, especially with alpha 5 GABA(A) receptors (alpha 5GABA(A)Rs), expression of which takes place between E14 and E17. Thereafter, we set to investigate if later potentiation of alpha 5GABA(A)Rs in offspring's preadolescence (from postnatal day 22-28) could prevent the deficit in locomotor reactivity to amphetamine observed in adulthood, at postnatal day P60. The elevation of IL-6 in amniotic fluid 6 h after LPS treatment (100 mu g/kg, i.p.) at E15 was concurrent with a significant increase of GABA and decrease of glutamate concentration in fetal brain. Moreover, repeated administration of MP-III-022, a selective positive allosteric modulator of alpha 5GABA(A)Rs, at a dose (2 mg/kg daily, i.p.) derived from a separate pharmacokinetic study, prevented the LPS-induced decrease in locomotor reactivity to amphetamine (0.5 mg/kg, i.p.) in adult females. These results were not mirrored in the parallel set of experiments with male offspring from LPS-treated rats. The results suggest that pharmacological potentiation of alpha 5GABA(A)Rs activity in preadolescence may ameliorate at least some of adverse consequences of exposure to MIA in utero.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "International Journal of Developmental Neuroscience",
title = "Positive modulation of alpha 5 GABA(A) receptors in preadolescence prevents reduced locomotor response to amphetamine in adult female but not male rats prenatally exposed to lipopolysaccharide",
volume = "61",
pages = "31-39",
doi = "10.1016/j.ijdevneu.2017.06.001"
}

Batinić, B., Santrač, A., Jančić, I., Li, G., Vidojević, A., Marković, B., Cook, J. M.,& Savić, M.. (2017). Positive modulation of alpha 5 GABA(A) receptors in preadolescence prevents reduced locomotor response to amphetamine in adult female but not male rats prenatally exposed to lipopolysaccharide. in International Journal of Developmental Neuroscience
Pergamon-Elsevier Science Ltd, Oxford., 61, 31-39.
https://doi.org/10.1016/j.ijdevneu.2017.06.001

Batinić B, Santrač A, Jančić I, Li G, Vidojević A, Marković B, Cook JM, Savić M. Positive modulation of alpha 5 GABA(A) receptors in preadolescence prevents reduced locomotor response to amphetamine in adult female but not male rats prenatally exposed to lipopolysaccharide. in International Journal of Developmental Neuroscience. 2017;61:31-39.
doi:10.1016/j.ijdevneu.2017.06.001 .

Batinić, Bojan, Santrač, Anja, Jančić, Ivan, Li, Guanguan, Vidojević, Aleksandra, Marković, Bojan, Cook, James M., Savić, Miroslav, "Positive modulation of alpha 5 GABA(A) receptors in preadolescence prevents reduced locomotor response to amphetamine in adult female but not male rats prenatally exposed to lipopolysaccharide" in International Journal of Developmental Neuroscience, 61 (2017):31-39,
https://doi.org/10.1016/j.ijdevneu.2017.06.001 . .

TY  - CONF
AU  - Petrović, Jelena
AU  - Labudović-Borović, Milica
AU  - Puškaš, Nela
AU  - Stanić, Dušanka
AU  - Batinić, Bojan
AU  - Plećaš-Solarović, Bosiljka
AU  - Pešić, Vesna
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2894
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - Chronic magnesium supplementation increases hippocampal neurogenesis and decreases proliferation in myocardium in ACTH-treated rats
VL  - 27
IS  - Supplement 4
SP  - S765
EP  - S766
DO  - 10.1016/S0924-977X(17)31398-6
ER  - 

@conference{
author = "Petrović, Jelena and Labudović-Borović, Milica and Puškaš, Nela and Stanić, Dušanka and Batinić, Bojan and Plećaš-Solarović, Bosiljka and Pešić, Vesna",
year = "2017",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "Chronic magnesium supplementation increases hippocampal neurogenesis and decreases proliferation in myocardium in ACTH-treated rats",
volume = "27",
number = "Supplement 4",
pages = "S765-S766",
doi = "10.1016/S0924-977X(17)31398-6"
}

Petrović, J., Labudović-Borović, M., Puškaš, N., Stanić, D., Batinić, B., Plećaš-Solarović, B.,& Pešić, V.. (2017). Chronic magnesium supplementation increases hippocampal neurogenesis and decreases proliferation in myocardium in ACTH-treated rats. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 27(Supplement 4), S765-S766.
https://doi.org/10.1016/S0924-977X(17)31398-6

Petrović J, Labudović-Borović M, Puškaš N, Stanić D, Batinić B, Plećaš-Solarović B, Pešić V. Chronic magnesium supplementation increases hippocampal neurogenesis and decreases proliferation in myocardium in ACTH-treated rats. in European Neuropsychopharmacology. 2017;27(Supplement 4):S765-S766.
doi:10.1016/S0924-977X(17)31398-6 .

Petrović, Jelena, Labudović-Borović, Milica, Puškaš, Nela, Stanić, Dušanka, Batinić, Bojan, Plećaš-Solarović, Bosiljka, Pešić, Vesna, "Chronic magnesium supplementation increases hippocampal neurogenesis and decreases proliferation in myocardium in ACTH-treated rats" in European Neuropsychopharmacology, 27, no. Supplement 4 (2017):S765-S766,
https://doi.org/10.1016/S0924-977X(17)31398-6 . .

TY  - CONF
AU  - Batinić, Bojan
AU  - Santrač, Anja
AU  - Jančić, Ivan
AU  - Marković, Bojan
AU  - Milić, Marija
AU  - Savić, Miroslav
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2872
PB  - Elsevier Science BV, Amsterdam
C3  - European Neuropsychopharmacology
T1  - GABA-A alpha 5 receptor potentiation in preadolescence prevents hyporeactivity to amphetamine induced by prenatal lipopolysaccharide treatment in rat females
VL  - 27
SP  - S610
EP  - S611
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2872
ER  - 

@conference{
author = "Batinić, Bojan and Santrač, Anja and Jančić, Ivan and Marković, Bojan and Milić, Marija and Savić, Miroslav",
year = "2017",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Neuropsychopharmacology",
title = "GABA-A alpha 5 receptor potentiation in preadolescence prevents hyporeactivity to amphetamine induced by prenatal lipopolysaccharide treatment in rat females",
volume = "27",
pages = "S610-S611",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2872"
}

Batinić, B., Santrač, A., Jančić, I., Marković, B., Milić, M.,& Savić, M.. (2017). GABA-A alpha 5 receptor potentiation in preadolescence prevents hyporeactivity to amphetamine induced by prenatal lipopolysaccharide treatment in rat females. in European Neuropsychopharmacology
Elsevier Science BV, Amsterdam., 27, S610-S611.
https://hdl.handle.net/21.15107/rcub_farfar_2872

Batinić B, Santrač A, Jančić I, Marković B, Milić M, Savić M. GABA-A alpha 5 receptor potentiation in preadolescence prevents hyporeactivity to amphetamine induced by prenatal lipopolysaccharide treatment in rat females. in European Neuropsychopharmacology. 2017;27:S610-S611.
https://hdl.handle.net/21.15107/rcub_farfar_2872 .

Batinić, Bojan, Santrač, Anja, Jančić, Ivan, Marković, Bojan, Milić, Marija, Savić, Miroslav, "GABA-A alpha 5 receptor potentiation in preadolescence prevents hyporeactivity to amphetamine induced by prenatal lipopolysaccharide treatment in rat females" in European Neuropsychopharmacology, 27 (2017):S610-S611,
https://hdl.handle.net/21.15107/rcub_farfar_2872 .