Date Approved
7-14-2025
Embargo Period
7-14-2027
Document Type
Dissertation
Degree Name
Ph.D. Biological and Biomedical Sciences
Department
Biological and Biomedical Sciences
College
College of Science & Mathematics
Advisor
Melissa Manners, Ph.D.
Committee Member 1
Maggie Pearce, Ph.D.
Committee Member 2
Ben Carone, Ph.D.
Committee Member 3
Isabelle Mercier, Ph.D.
Committee Member 4
Jessica Loweth, Ph.D.
Keywords
Astrocytes;Chronic stress;Inflammation;Microglia;Opioid receptor;Sex difference
Disciplines
Biology | Life Sciences
Abstract
Chronic stress has been associated with increased inflammation in the brain. As the primary immune regulators, microglia and astrocytes are negatively impacted by the effects of chronic stress. In this study, chronic stress induced weight loss and avoidance behavior in males only; however, the stress-induced microglia and astrocyte activation was observed from multiple brain regions in both sexes. Independent of chronic stress, microglia also exhibited an activated baseline phenotype in a sex and region-specific manner, suggesting a higher inflammatory profile at different brain regions in females. Furthermore, we also explored the role of the mu opioid receptor (MOR) in modulating astrocyte reactivity and found that the inhibition of MOR did not affect astrocyte reactivity in vitro. However, buprenorphine (BUP), a MOR partial agonist, decreased the stress-induced activation phenotype in microglia and astrocytes across the brain, suggesting that the MOR-modulated astrocyte reactivity may be dependent on other cell types. In addition, BUP also exerted a cell-type and region-specific effect on microglia, independent of stress. Our findings suggested that while BUP-mediated MOR activation can attenuate the stress-induced glia activation, microglia and astrocytes respond to the effect of BUP and stress with a sex and region-specific phenotype and degree of activation.
Recommended Citation
Zhang, Ariel Y., "Heterogeneity of Glial Reactivity: Brain Region and Sex Specific Response to Chronic Stress" (2025). Theses and Dissertations. 3431.
https://rdw.rowan.edu/etd/3431
