Effect of chronic social isolation stress after acute traumatic stress on mouse social behavior across the life cycle

초록

Background Modern people are exposed to various stressful situations. Stress is a crucial factor for depression and is related to the imbalance of physiological and psychological homeostasis, including brain function and structure. Stress induces the endocrine alterations characterized by the activation of hypothalamic-pituitary-adrenal axis and sympathetic adrenal-medullary system. There are many causes of stress, and each affects us differently. However, it remains unknown how transcriptomic alteration induced by long-term social isolation stress are occurred in the hippocampus regions. Therefore, we used next-generation sequencing (NGS) to profile the transcriptomic changes in mice which could induce behavior changes after long-term social isolation stress. Therefore, we focused on the effect of long-term social isolation stress on mice behavior in each life cycle model by age. Interestingly, we observed different behavioral phenotype in childhood stage compared with early adulthood and adulthood stage. Methods We focused on the effect of long-term social isolation stress on mice behavior in each life cycle model by age. C57Bl/6J male mice of Childhood, early adulthood, and adulthood were performed a behavioral test after 5 weeks of social isolation after 1 week of severe acute stress. we observed that 5 weeks of social isolation led to different behavioral phenotype in childhood compared with the early adulthood and adulthood stages. Results We observed different behavioral phenotype in childhood stage compared with early adulthood and adulthood stage. Long-term social isolation-induced childhood male mice showed high social dominance in the tube dominance test and increased serum CORT levels. The Gene ontology (GO) analysis of Differential Express Genes (DEGs) with significant differences revealed that they are involved in critical biological processes and molecular pathways, such as neuron differentiation, neurogenesis, neuron development, learning or memory, brain development, and neuroactive ligand-receptor interaction. Finally, DEGs analysis revealed that 4 candidate genes were up-regulated, and 4 down-regulated genes. The differential expression of the selected genes were verified using by qRT‒PCR and immunohistochemistry (IHC). Therefore, we identified the effect of social isolation on the development of sociability through age by transcriptome analysis that were associated with social behavior, including FABP7 and Cxcl12. Conclusions Through this study, we can find the critical factor involved in the sociability that might be utilized to the diagnosis indicators or therapeutic agents for stress-related diseases.