Acth-induced model of depression resistant to tricyclic antidepressants: Neuroendocrine and behavioral changes and influence of long-term magnesium administration
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2018
Authors
Petrović, JelenaStanić, Dušanka
Bulat, Zorica
Puskas, Nela
Labudović-Borović, Milica
Batinić, Bojan
Mirković, Duško
Ignjatović, Svetlana
Pešić, Vesna
Article (Published version)
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Show full item recordAbstract
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 pr...evented 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.
Keywords:
Major depressive disorder / Adrenocorticotropic hormone / Treatment resistant depression / Magnesium / NeurogenesisSource:
Hormones and Behavior, 2018, 105, 1-10Publisher:
- Academic Press Inc Elsevier Science, San Diego
Funding / projects:
- Biomarkers of organ damage and dysfunction (RS-MESTD-Basic Research (BR or ON)-175036)
DOI: 10.1016/j.yhbeh.2018.07.003
ISSN: 0018-506X
PubMed: 30025718
WoS: 000452246600001
Scopus: 2-s2.0-85050162395
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Institution/Community
PharmacyTY - 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 . .