Proteome profile of Nucleus Accumbens (NAc) uncovers the differential and sex-specific role of CRMP2 in CVMS induced mouse model of depression

Chronic stress plays a very important role in building pathogenesis of psychiatric disorders including major depressive disorder (MDD). Despite of the fact that the human females are more prone to stress vulnerability, molecular mechanisms of depression-like pathophysiology in female rodent models is less studied as compared to that in males. Previous reports showed that 6-days of chronic unpredictable stress (CUS) paradigm can induce depression-like mood disorders in female mice whereas 21-days of chronic variable multiple stress (CVMS) paradigm induces the similar phenotypes in both the sexes. The gene array studies on critically affected areas like nucleus accumbens (NAc) and hypothalamus have indicated that the molecular mechanisms underlying the stress susceptibility might be differentially regulated across the sexes. However, there is scarcity of studies on proteome changes associated with MDD. In this study we specifically attempted to identify altered protein expression in NAc of OVX, as well as both male and female mice on CVMS using 2-DE followed by MALDI-LC-MS/MS. From 2D gel analysis total of 46 significantly altered protein spots were selected (20 proteins in OVX female, 7 in the male and 19 in the intact female) and identified by MALDI-LC-MS/MS. Proteomics data followed by validation revealed dysregulation of neuropeptide, Collapsin response mediator protein-2, CRMP2 (also known as DPYSL2), crucial for neuronal growth and is known to be associated with neurodegenerative/psychiatric disorders. These findings suggest the importance of comprehending the function of these proteins in a significantly affected brain area under long-term stress conditions to address the occurrence and symptoms of depression in both men and women.