Metabolic and Transcriptomic Signatures of the Acute Psychological Stress Response in the Mouse Brain

Acute stress response triggers various physiological responses such as energy mobilization to meet metabolic demands. However, the underlying molecular changes in the brain remain largely obscure. Here, we used a brief water avoidance stress (WAS) to elicit an acute stress response in mice. By employing RNA-sequencing and metabolomics profiling, we investigated the acute stress-induced molecular changes in the mouse whole brain. The aberrant expression of 60 genes was detected in the brain tissues of WAS-exposed mice. Functional analyses showed that the aberrantly expressed genes were enriched in various processes such as superoxide metabolism. In our global metabolomic profiling, a total of 43 brain metabolites were significantly altered by acute WAS. Metabolic pathways upregulated from WAS-exposed brain tissues relative to control samples included lipolysis, eicosanoid biosynthesis, and endocannabinoid synthesis. Acute WAS also elevated the levels of branched-chain amino acids, 5-aminovalerates, 4-hydroxy-nonenal-glutathione as well as mannose, suggesting complex metabolic changes in the brain. The observed molecular events in the present study provide a valuable resource that can help us better understand how acute psychological stress impacts neural functions.

Automated summary

Acute stress response leads to various physiological changes in the brain, including altered gene expression and metabolic pathways. In this study, mice exposed to a brief water avoidance stress (WAS) showed aberrant expression of 60 genes and significant changes in 43 brain metabolites. Functional analysis revealed enrichment of genes involved in superoxide metabolism, while metabolomic profiling showed upregulation of lipolysis, eicosanoid biosynthesis, and endocannabinoid synthesis pathways. These findings provide valuable insights into the molecular events underlying acute stress and its impact on neural functions.