Influence of Sex on Stress-Induced Changes in Physical Activity and Gene Expression

A sedentary lifestyle poses significant health risks, contributing to various chronic diseases. Stress has been identified as a factor influencing physical activity levels, suggesting a complex relationship between psychological stressors and exercise behavior. In male rats, exposure to tail shock stress induces persistent physical inactivity, as evidenced by decreased voluntary wheel running (VWR) activity. In contrast, female rats do not exhibit the same degree of inactivity following tail shock stress, suggesting a potential sex difference in the regulation of exercise behavior under stress. To investigate whether estrogen regulates the effects of stress on exercise, we examined VWR activity in female rats following bilateral ovariectomy (OVX) to deplete endogenous estrogen. No significant differences in running activity were observed between stressed and control OVX groups, nor in their response to exogenously administered estrogen. These findings suggest that sex differences in stress-induced physical inactivity may occur independently of estrogen. Based on our observations of persistent inactivity in males following stress, we hypothesized that stress induces long-lasting molecular changes in brain regions critical for movement and motivation. To explore this, we analyzed single-nucleus RNA sequencing (snRNA-seq) datasets from the striatum, a key hub for motor control and reward processing. Our preliminary findings reveal distinct gene expression patterns associated with exercise, stress, and their interaction, particularly in oligodendrocytes, which are essential for neuronal support and myelination. These findings provide an initial framework for understanding the molecular basis of stress-induced physical inactivity. Ongoing research will further examine the involvement of additional cell types and neural circuits within the striatum to elucidate the pathways linking stress to long-term reductions in physical activity. Iowa Osteopathic Education and Research Foundation 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.