Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine
Само за регистроване кориснике
2017
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21 days of chronic social isolation (CSIS). We also tested the ability of FLX (15 mg/kg/day) or CLZ (20 mg/kg/day), applied during CSIS, to prevent stress-induced changes. CSIS caused depressive-and anxiety-like behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B (NF-kappa B) activation with a concomitant increase i...n cytosolic levels of proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis factor-alpha in the PFC. NF-kappa B activation and proinflammatory response in the PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS-induced GSH depletion, but it diminished its levels when applied to non-stressed rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory response underlying depressive-and anxiety-like states induced by CSIS were prevented by FLX. The protective effect of CLZ, which was equally effective as FLX on the behavioral level, was limited to proinflammatory components. Hence, different mechanisms underlie the protective effects of these two drugs in CSIS rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Кључне речи:
chronic social isolation / fluoxetine / clozapine / prefrontal cortex / glutathione / proinflammatory mediatorsИзвор:
Neuroscience, 2017, 355, 49-60Финансирање / пројекти:
DOI: 10.1016/j.neuroscience.2017.04.044
ISSN: 0306-4522; 1873-7544
PubMed: 28499974
WoS: 000404075700005
Scopus: 2-s2.0-85019345609
Колекције
Институција/група
VinčaTY - JOUR AU - Todorović, Nevena AU - Filipović, Dragana PY - 2017 UR - https://vinar.vin.bg.ac.rs/handle/123456789/1613 AB - Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21 days of chronic social isolation (CSIS). We also tested the ability of FLX (15 mg/kg/day) or CLZ (20 mg/kg/day), applied during CSIS, to prevent stress-induced changes. CSIS caused depressive-and anxiety-like behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B (NF-kappa B) activation with a concomitant increase in cytosolic levels of proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis factor-alpha in the PFC. NF-kappa B activation and proinflammatory response in the PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS-induced GSH depletion, but it diminished its levels when applied to non-stressed rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory response underlying depressive-and anxiety-like states induced by CSIS were prevented by FLX. The protective effect of CLZ, which was equally effective as FLX on the behavioral level, was limited to proinflammatory components. Hence, different mechanisms underlie the protective effects of these two drugs in CSIS rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved. T2 - Neuroscience T1 - Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine VL - 355 SP - 49 EP - 60 DO - 10.1016/j.neuroscience.2017.04.044 ER -
@article{ author = "Todorović, Nevena and Filipović, Dragana", year = "2017", abstract = "Chronic psychosocial stress modulates brain antioxidant systems and causes neuroinflammation that plays a role in the pathophysiology of depression. Although the antidepressant fluoxetine (FLX) represents the first-line treatment for depression and the atypical antipsychotic clozapine (CLZ) is considered as a second-line treatment for psychotic disorders, the downstream mechanisms of action of these treatments, beyond serotonergic or dopaminergic signaling, remain elusive. We examined behavioral changes, glutathione (GSH)-dependent defense and levels of proinflammatory mediators in the prefrontal cortex (PFC) of adult male Wistar rats exposed to 21 days of chronic social isolation (CSIS). We also tested the ability of FLX (15 mg/kg/day) or CLZ (20 mg/kg/day), applied during CSIS, to prevent stress-induced changes. CSIS caused depressive-and anxiety-like behaviors, compromised GSH-dependent defense, and induced nuclear factor-kappa B (NF-kappa B) activation with a concomitant increase in cytosolic levels of proinflammatory mediators cyclooxigenase-2, interleukin-1beta and tumor necrosis factor-alpha in the PFC. NF-kappa B activation and proinflammatory response in the PFC were not found in CSIS rats treated with FLX or CLZ. In contrast, only FLX preserved GSH content in CSIS rats. CLZ not only failed to protect against CSIS-induced GSH depletion, but it diminished its levels when applied to non-stressed rats. In conclusion, prefrontal cortical GSH depletion and the proinflammatory response underlying depressive-and anxiety-like states induced by CSIS were prevented by FLX. The protective effect of CLZ, which was equally effective as FLX on the behavioral level, was limited to proinflammatory components. Hence, different mechanisms underlie the protective effects of these two drugs in CSIS rats. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.", journal = "Neuroscience", title = "Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine", volume = "355", pages = "49-60", doi = "10.1016/j.neuroscience.2017.04.044" }
Todorović, N.,& Filipović, D.. (2017). Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine. in Neuroscience, 355, 49-60. https://doi.org/10.1016/j.neuroscience.2017.04.044
Todorović N, Filipović D. Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine. in Neuroscience. 2017;355:49-60. doi:10.1016/j.neuroscience.2017.04.044 .
Todorović, Nevena, Filipović, Dragana, "Prefrontal Cortical Glutathione-Dependent Defense and Proinflammatory Mediators in Chronically Isolated Rats: Modulation By Fluoxetine Or Clozapine" in Neuroscience, 355 (2017):49-60, https://doi.org/10.1016/j.neuroscience.2017.04.044 . .