Date of Award

Summer 2023

Document Type

Open Access Dissertation

Department

Exercise Science

First Advisor

J. Mark Davis

Second Advisor

Susan K. Wood

Abstract

Social stress is the most common form of stress humans experience and often precipitates the onset of several comorbidities, including anxiety, depression, post-traumatic stress disorder, and cardiovascular diseases. While many individuals experience social stress and can respond, cope, and recover, some individuals are more likely to develop subsequent health conditions. Importantly, women are particularly susceptible to stress-related disorders, and the prevalence rates for these comorbid conditions are 2-3-fold higher among females compared to males. Epidemiological data suggest that cycling ovarian hormones may play a role in promoting stress susceptibility in females. Therefore, the current studies aimed to examine the effects of social stress exposure on the neuronal, behavioral, cardiovascular, and physiological responses in females using a preclinical model of social stress known as witness stress. In this model, a female rat observes an aggressive social defeat encounter between two male rats. Therefore, this preclinical model serves as an ethologically and clinically relevant model of social stress. Using this witness stress model, we identified that estrogen signaling is critical in generating the neural, behavioral, and peripheral responses observed in adult female rats. Additionally, because neuroimmune signaling in response to stress has been identified as a critical factor promoting psychiatric and cardiovascular comorbidities, we examined the role for microglia, the brain’s primary immune cell, in promoting stress-evoked responses in female rats. We identified that microglia in the stress-sensitive locus coeruleus facilitate stress-evoked behavior and autonomic changes. Finally, given the high levels of treatment resistance associated with stress-related disorders, we examined the impact of short-term voluntary wheel running on witness stress-evoked behavioral, autonomic, and neural responses. We identified a trend in which three weeks of voluntary wheel running exerts protective effects in the context of social stress, particularly by enhancing vagal tone. Together, these data highlight key mechanistic factors contributing to heightened stress susceptibility among females and suggest that exercise is a valuable therapeutic tool for promoting stress resilience.

Rights

© 2023, Brittany Sara Pate

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