Dynamic effects of chronic unpredictable mild stress on the hippocampal transcriptome in rats

Stress causes extensive changes in hippocampal genomic expression, leading to changes in hippocampal structure and function. The dynamic changes in hippocampal gene expression caused by stress of different durations are still unknown. mRNA sequencing was used to analyze the hippocampal transcriptome of rats subjected to chronic unpredictable mild stress (CUMS) of different durations. Compared with the control, 501, 442 and 235 differentially expressed genes (DEGs) were detected in the hippocampus of rats subjected to CUMS for 3 days and 2 and 6 weeks, respectively. Gene Ontology (GO) analysis was used to determine the potential mechanism underlying the dynamic harmful effects of stress on the hippocampus; Certain GO terms of the down-regulated DEGs in CUMS (3 days) rats were also found in the up-regulated DEGs in CUMS (6 weeks) rats. These results showed opposing regulation patterns of DEGs between CUMS at 3 days and 6 weeks, which suggested a functional change from adaptation to damage in during the early and late stages of chronic stress. GO analysis for upregulated genes in rats subjected to CUMS for 3 days and 2 weeks suggested significant changes in ‘extracellular matrix’ and ‘wound healing’. Upregulated genes in rats subjected to CUMS for 2 weeks were involved in changes associated with visual function. GO analysis of DEGs in rats subjected to CUMS for 6 weeks revealed increased expression of genes associated with ‘apoptotic process’ and ‘aging’ and decreased expression of those associated with inhibition of cell proliferation and cell structure. These results suggest that the early and middle stages of chronic stress primarily promote adaptive regulation and damage repair in the organism, while the late stage of chronic stress leads to damage in the hippocampus.