Effect of social interactions on hippocampal protein expression in animal dominant and submissive model of behavioral disorders

Purpose: Psychiatric conditions, in many cases, arise from social interactions necessary for optimal mental functioning. Dominance and submissiveness are two opposite poles of behavior, stemming from processes of social interactions between members inside one group or species. Extreme dominance and submissiveness expressions in humans is accompanied by mental impairments, including mania and depression. Here, taking advantage of animals bred selectively for traits of dominance and submissiveness, we assess protein expression profiles in dominant and submissive mice in the context of social interaction. Experimental design: Proteins extracted from hippocampi of naïve and social interaction subjected dominant, submissive and wild type mice (15 mice per each group) are quantified using label-free quantitative LC/MS/MS analysis. Complexity of social interaction-related protein expression is resolved by factor analysis and enriched with GO and protein-protein interaction functional network analyses. Results: In total, 1146 proteins exhibiting expression changes in the wild type mice, as well as dominant and submissive mice are enriched in protein datasets responsible for: 1) socially triggered dominance (90 proteins), 2) inherent submissiveness (75 proteins), 3) socially triggered submissiveness (117 proteins), and 4) social interaction triggered protein expression changes, related to resilience/adaptation to stress (69 proteins). Among the most enriched categories, extensive changes are found in proteins related to presynaptic release, ion channel regulation, circadian rhythm, MAPK, ErbB and NF-kB pathways. Conclusion: Data extracted from this first extensive proteomic study of a social interaction paradigm may facilitate decoding of molecular mechanisms responsible for pathogenesis of psychiatric disorders.