TY  - JOUR
AU  - Martinović, Jelena
AU  - Samardžić, Janko
AU  - Zarić Kontić, Marina
AU  - Ivković, Sanja
AU  - Dacić, Sanja
AU  - Major, Tamara
AU  - Radosavljević, Milica
AU  - Švob Štrac, Dubravka
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5407
AB  - Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.
PB  - MDPI
T2  - Brain Sciences
T1  - Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus
VL  - 13
IS  - 12
DO  - 10.3390/brainsci13121707
ER  - 

@article{
author = "Martinović, Jelena and Samardžić, Janko and Zarić Kontić, Marina and Ivković, Sanja and Dacić, Sanja and Major, Tamara and Radosavljević, Milica and Švob Štrac, Dubravka",
year = "2023",
abstract = "Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.",
publisher = "MDPI",
journal = "Brain Sciences",
title = "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus",
volume = "13",
number = "12",
doi = "10.3390/brainsci13121707"
}

Martinović, J., Samardžić, J., Zarić Kontić, M., Ivković, S., Dacić, S., Major, T., Radosavljević, M.,& Švob Štrac, D.. (2023). Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences
MDPI., 13(12).
https://doi.org/10.3390/brainsci13121707

Martinović J, Samardžić J, Zarić Kontić M, Ivković S, Dacić S, Major T, Radosavljević M, Švob Štrac D. Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences. 2023;13(12).
doi:10.3390/brainsci13121707 .

Martinović, Jelena, Samardžić, Janko, Zarić Kontić, Marina, Ivković, Sanja, Dacić, Sanja, Major, Tamara, Radosavljević, Milica, Švob Štrac, Dubravka, "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus" in Brain Sciences, 13, no. 12 (2023),
https://doi.org/10.3390/brainsci13121707 . .

TY  - JOUR
AU  - Ćupić Miladinović, Dejana
AU  - Prevendar Crnić, Andreja
AU  - Peković, Sanja
AU  - Dacić, Sanja
AU  - Ivanović, Saša
AU  - Santibanez, Juan Francisco
AU  - Ćupić, Vitomir
AU  - Borozan, Nevena
AU  - Antonijević-Miljaković, Evica
AU  - Borozan, Sunčica
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3810
AB  - Chlorpyrifos is a extensively used organophosphate pesticide (OP). In this study, we closely looked into neurotoxicity of CPF and effect of vitamin B1, by checking the levels of cholinesterases, determining the activity of parameters of oxidative stress, inflammation and also level of apoptotic regulator. The study was performed on a total of 80 male Japanese quails (Coturnix japonica), (two control and 6 experimental groups, n = 10). Three group of quails were given by gavage chlorpyrifos (CPF) for 7 consecutive days at doses of 1.50 mg/kg b.w., 3.00 mg/kg b.w., and 6.00 mg/kg b.w. Another three groups were treated with 10 mg/kg b.w. of vitamin B1 i.m. 30 min after CPF application (in above mentioned doses). Our study have proved that all doses of CPF significantly inhibited cholinesterases in brain, while vitamin B1 reactivated them. CPF has led to an increase in the concentration of malondialdehyde (MDA), and activity of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), while tiamin changed the activity of antioxidant enzymes: CAT, SOD, GST. CPF stimulated apoptosis by decreasing B-cell lymphoma (Bcl-2) in brain, while application of vitamin B1 caused an increase of this parameter. CPF amplified inflammatory effect by elevating levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Thiamine proved its anti-inflammatory property by decreasing the expression of iNOS and interleukin-1(IL-1) and interleukin-6(IL-6). This study is highly pertinent because there is little defense currently available to humans and animals to prevent toxic effects of pesticides.
PB  - Elsevier Ireland Ltd
T2  - Chemico-Biological Interactions
T1  - Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration
VL  - 333
DO  - 10.1016/j.cbi.2020.109312
ER  - 

@article{
author = "Ćupić Miladinović, Dejana and Prevendar Crnić, Andreja and Peković, Sanja and Dacić, Sanja and Ivanović, Saša and Santibanez, Juan Francisco and Ćupić, Vitomir and Borozan, Nevena and Antonijević-Miljaković, Evica and Borozan, Sunčica",
year = "2021",
abstract = "Chlorpyrifos is a extensively used organophosphate pesticide (OP). In this study, we closely looked into neurotoxicity of CPF and effect of vitamin B1, by checking the levels of cholinesterases, determining the activity of parameters of oxidative stress, inflammation and also level of apoptotic regulator. The study was performed on a total of 80 male Japanese quails (Coturnix japonica), (two control and 6 experimental groups, n = 10). Three group of quails were given by gavage chlorpyrifos (CPF) for 7 consecutive days at doses of 1.50 mg/kg b.w., 3.00 mg/kg b.w., and 6.00 mg/kg b.w. Another three groups were treated with 10 mg/kg b.w. of vitamin B1 i.m. 30 min after CPF application (in above mentioned doses). Our study have proved that all doses of CPF significantly inhibited cholinesterases in brain, while vitamin B1 reactivated them. CPF has led to an increase in the concentration of malondialdehyde (MDA), and activity of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), while tiamin changed the activity of antioxidant enzymes: CAT, SOD, GST. CPF stimulated apoptosis by decreasing B-cell lymphoma (Bcl-2) in brain, while application of vitamin B1 caused an increase of this parameter. CPF amplified inflammatory effect by elevating levels of inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Thiamine proved its anti-inflammatory property by decreasing the expression of iNOS and interleukin-1(IL-1) and interleukin-6(IL-6). This study is highly pertinent because there is little defense currently available to humans and animals to prevent toxic effects of pesticides.",
publisher = "Elsevier Ireland Ltd",
journal = "Chemico-Biological Interactions",
title = "Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration",
volume = "333",
doi = "10.1016/j.cbi.2020.109312"
}

Ćupić Miladinović, D., Prevendar Crnić, A., Peković, S., Dacić, S., Ivanović, S., Santibanez, J. F., Ćupić, V., Borozan, N., Antonijević-Miljaković, E.,& Borozan, S.. (2021). Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration. in Chemico-Biological Interactions
Elsevier Ireland Ltd., 333.
https://doi.org/10.1016/j.cbi.2020.109312

Ćupić Miladinović D, Prevendar Crnić A, Peković S, Dacić S, Ivanović S, Santibanez JF, Ćupić V, Borozan N, Antonijević-Miljaković E, Borozan S. Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration. in Chemico-Biological Interactions. 2021;333.
doi:10.1016/j.cbi.2020.109312 .

Ćupić Miladinović, Dejana, Prevendar Crnić, Andreja, Peković, Sanja, Dacić, Sanja, Ivanović, Saša, Santibanez, Juan Francisco, Ćupić, Vitomir, Borozan, Nevena, Antonijević-Miljaković, Evica, Borozan, Sunčica, "Recovery of brain cholinesterases and effect on parameters of oxidative stres and apoptosis in quails (Coturnix japonica) after chlorpyrifos and vitamin B1 administration" in Chemico-Biological Interactions, 333 (2021),
https://doi.org/10.1016/j.cbi.2020.109312 . .