Sex-Specific Differential Gene Expression Following a Single Bout of Exercise in Mice

Although many studies have demonstrated the beneficial effects of chronic exercise on brain gene expression, the transcriptomic changes induced by acute exercise and their sex-specific mechanisms remain underexplored. This study investigated sex-specific exercise-induced gene expression changes in the hippocampus of male and female C57BL/6 mice following a single bout of exercise. Mice ran on a treadmill at 20 meters per minute for one hour and brain tissue was collected immediately afterward. Bulk RNA sequencing was performed, and differentially expressed genes and gene ontology pathways analyzed. The single bout of exercise significantly altered hippocampal gene expression in a sex-specific manner. In females, 70 genes were up-regulated while 2 were down-regulated. Eighteen genes were up-regulated in males. Gene ontology enrichment analysis identified shared pathways between sexes, including long-term memory, transcription regulation, and cell differentiation. Additionally, sex-specific pathways were amplified. For example, vasculogenesis was enriched in females, whereas the cellular response to calcium ion pathway was increased in males. These findings provide insights into the molecular mechanisms underlying exercise-induced neuroplasticity in a sex-specific manner. MSU Biomedical Sciences program This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.