Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: depression-like behaviour and fluoxetine mechanism of action

Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to dise...

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Main Authors: Peric, Ivana (Author) , Costina, Victor (Author) , Findeisen, Peter (Author)
Format: Article (Journal)
Language:English
Published: June 2018
In: Neuropharmacology
Year: 2018, Volume: 135, Pages: 268-283
ISSN:1873-7064
DOI:10.1016/j.neuropharm.2018.03.034
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.neuropharm.2018.03.034
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0028390818301461
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Author Notes:Ivana Perić, Victor Costina, Andrijana Stanisavljević, Peter Findeisen, Dragana Filipović

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520 |a Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to disease and treatment. As chronic social isolation (CSIS) is a valuable animal model for studying depression, we performed a comparative subproteomic study of rat hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15mg/kg/day). Behaviorally, Flx treatment normalized the decreased sucrose preference and increased marble burying results resulting from CSIS, indicative of a FLX-induced attenuation of both anhedonia and anxiety. An analysis of cytosolic and nonsynaptic mitochondrial subproteome patterns revealed that CSIS resulted in down-regulation of proteins involved in mitochondrial transport and energy processes, primarily tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Chronic Flx treatment resulted in an up-regulation of CSIS-altered proteins and additional expression of other transporter and energy-involved proteins. Immunohistochemical analysis revealed hippocampal subregion-specific effects of CSIS and/or Flx treatment on selective protein expressions. 
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