A Preliminary Study On Hippocampal Proteomics Of The Chronic Social Defeat Stress Mice

Major depressive disorder(MDD)is a highly prevalent and complex mental disease concomitant with obvious impairment in social functioning,which is characterized by sustained low mood and anhedonia.Although decades of research have revealed numerous molecular abnormalities in the hippocampus associated with depression,the different mechanisms involved in the susceptibility and resilience of mice to chronic social defeat stress(CSDS)-induced depression remain poorly understand.Through the social defeat model,we can study the differences in molecular changes between the susceptible and resilient mice.We used a proteomic-based platform to compare hippocampal proteins in CSDS mice with those in control mice.Differentially expressed proteins were identified through isobaric tags for relative and absolute quantitation(iTRAQ)combined with LC-MS/MS.We then analyzed the results by ingenuity pathway analysis(IPA)and verified proteins by western blotting.Mice were exposed to 10 days of CSDS,which successfully induced stress-susceptible and-resilient phenotypes.161 and 134 proteins weresignificantly differentially expressed in the susceptible and resilient groups,respectively,compared with the levels in the control group.The resilient and the susceptible mice existed 108 proteins that were significant differentially expressed.The Rac signaling was the common top-ranking pathways among the three groups.We found that low-density lipoprotein receptor–related protein 6(LRP6)was upregulated in resilient mice and neuropeptide Y(NPY)was downregulated in susceptible mice compared with the levels in control mice.Moreover,neuropeptide Y receptor type 2(NPY2R)protein expression in susceptible mice was downregulated compared with that in the resilient group.Our findings in the three groups potentially reveal the differences in molecular mechanisms underlying depression between susceptible and resilient mice.The molecular mechanisms and causative reasons for MDD regulation are of great interest and require continuous studies.The results provide insight into molecular abnormalities of the hippocampus in CSDS mice and some potential drug targets for treating depression.