Hippocampal Proteomic Changes Of Susceptibility And Resilience To Depression Or Anxiety In A Rat Model Of Chronic Mild Stress

BackgroundChronic stressful occurrences are documented as a vital cause of both depression and anxiety disorders.However,the stress-induced molecular mechanisms underlying common and distinct pathophysiology of these disorders remain largely unclear.Methods Here,we utilized chronic mild stress(CMS)rat model to differentiate and subgroup depression-susceptible,anxiety-susceptible and insusceptible rats.The hippocampus was analyzed for differential proteomes by combining mass spectrometry and isobaric tags for relative and absolute quantitation(iTRAQ)labeling technique,bioinformatics analysis and immunoblot analysis.ResultsOf the 2593 quantified proteins,367 were aberrantly expressed and these hippocampal protein candidates might be associated withsusceptibility to stress-induced depression or anxiety and stress resilience.They provide potential protein systems involved in various metabolic pathways as novel investigative protein targets.Further,independent immunoblot analysis identified changes in Esd,Por,and Idh2;G6pdx,Glo1,Dld,and Aldh2;Dlat,Ogdhl,Anxal,Tpp2,and Sdha that were specifically associated to depression-susceptible,anxiety-susceptible or insusceptible groups respectively,suggesting that identical CMS differently impacted the mitochondrial and metabolic processes in the hippocampus.ConclutionCollectively,the observed alterations to protein abundance profiles of the hippocampus provided significant and novel insights into the stress regulation mechanism in a CMS rat model.This might serve as the molecular basis for further studies that would contributed to a better understanding of the similarities and differences in pathophysiologic mechanisms underlying stress-induced depression or anxiety,and stress resiliency.