Hippocampal mRNA expression profiling in mice exposed to chronic unpredictable mild stress

Abstract

Depression is a state of low mood and aversion to activity, affecting a person's thoughts, behavior, motivation, feelings and sense of well-being, which is associated with dramatical gene expression changes in hippocampus. Rodents induced by chronic unpredictable mild stress (CUMS) demonstrate typical depression-like behaviors similar to clinical patients, therefore, are commonly used as a model for depression and antidepressant study. In order to enhance our understanding of the molecular mechanisms of the pathogenesis of depression, in the present study, the hippocampal mRNA expression profile of mice exposed to CUMS for 5 weeks was sequenced using Illumina HiSeq 4000 platform followed by enrichment analysis, including Hierarchical Cluster, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network. Totally, 346 differently expressed mRNAs, including 208 downregulated and 138 upregulated, were identified in the hippocampus of the CUMS mice. KEGG biological pathway analysis showed that the upregulated and downregulated mRNAs were mostly enriched in 29 pathways and 8 pathways, respectively. PPI network analysis exposed that glyceraldehyde 3-phosphate dehydrogenase was the crucial node with high connectivity degree. Additionally, most of these genes in PPI network analysis have previously been linked to energy metabolism and corticosterone responses. Overall, our results indicate the possible novel molecular targets for the therapy of depression.