Central and peripheral changes underlying susceptibility and resistance to social defeat stress – A proteomic profiling study

Abstract

The social defeat mouse model is used as a preclinical model for major depressive disorder (MDD). This model is of interest, as mice subjected to chronic social defeat can be separated into stress susceptible (SS) and resilient (SR) subgroups that differ in defined behavioural and physiological characteristics. Here, we have carried out proteomic analyses of serum and brain samples from SS (n=12), SR (n=12) and unstressed control (n=12) mice, using two analytical platforms to gain insight into the underlying molecular pathways that distinguish these subgroups. Multiplex immunoassay profiling was performed using sera collected after 10 days of chronic social defeat. This analysis identified peripheral alterations in proteins mostly associated with inflammation in SS mice, whereas growth factors and hormones were changed predominantly in the SR subgroup. Label free liquid chromatography mass spectrometry (LC–MS^E) profiling of frontal cortex revealed a significant increase in myelin-associated proteins [2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CN37), mylein basic protein (MBP), and myelin proteolipid protein (MYPR)] in the SR group, suggesting that resilience to social stress might be mediated through activation of oligodendrogenesis. Taken together, these results provide the first proteomic evidence of differential effects on oligodendrocyte function between susceptible and resilient subgroups in the social defeat model and suggest that neuronal conductivity or central nervous system maintenance in the frontal cortex are involved in the adaptive response to stress. These changes appear to be reflected by serum alterations in inflammation and growth-related proteins, which could be used as biomarkers for predicting or monitoring stress response.