Abstract
Depression is a common and disabling mental disorder characterized by high disability and mortality, but its physiopathology remains unclear. In this study, we combined a non-targeted gas chromatography-mass spectrometry (GC-MS)-based metabolomic approach and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis to elucidate metabolite and protein alterations in the hippocampus of rat after chronic social defeat stress (CSDS), an extensively used animal model of depression. Ingenuity pathway analysis (IPA) was conducted to integrate underlying relationships among differentially expressed metabolites and proteins. Twenty-five significantly different expressed metabolites and 234 differentially expressed proteins were identified between CSDS and control groups. IPA canonical pathways and network analyses revealed that intracellular second messenger/signal transduction cascades were most significantly altered in the hippocampus of CSDS rats, including cyclic adenosine monophosphate (cAMP), phosphoinositol, tyrosine kinase, and arachidonic acid systems. These results provide a better understanding of biological mechanisms underlying depression, and may help identify potential targets for novel antidepressants.
Highlights
Depression is one of the most prevalent psychiatric and disability diseases conditions in the world today, but its physiopathology remains poorly elucidated (Health TNIoM, 2016; World Health Organization [WHO], 2017)
We conducted an integrated analysis of GC–MS-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to investigate molecular changes in the hippocampus of rats induced by chronic social defeat stress (CSDS)
KEGG pathway analysis based on differentially expressed proteins revealed that sphingolipid signaling, cyclic adenosine monophosphate (cAMP) signaling, and neurotrophin signaling, which have previously been associated with depression, are the main signaling pathways activated in the hippocampus of CSDS rats (Gould and Manji, 2002; Niciu et al, 2013)
Summary
Depression is one of the most prevalent psychiatric and disability diseases conditions in the world today, but its physiopathology remains poorly elucidated (Health TNIoM, 2016; World Health Organization [WHO], 2017). The repeated exposure of rodents to social defeat causes a solid depression-like behavior marked by anhedonia, body weight alteration, and altered protein expression in various brain areas (Vyas et al, 2002; Radley and Morrison, 2005; Denmark et al, 2010). Neuropathological studies of hippocampus showed atrophy of hippocampal neurons (Sousa et al, 2000; Harrison, 2002; Lucassen et al, 2006; McEwen, 2010). How these changes in hippocampus lead to depression still unclear (Christoffel et al, 2011). Revealing these molecular events is essential for understanding the pathogenesis of depression
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