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Sex-specific Responses to Glucocorticoids in Murine Immortalized Hippocampal Neurons and Intact Adult Brain

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Title: Sex-specific Responses to Glucocorticoids in Murine Immortalized Hippocampal Neurons and Intact Adult Brain
Author: Craig, Emily
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: MacLusky, Neil
Abstract: Males and females differ in their stress responses, and this is coupled with a sex difference in stress-related mood and anxiety disorders. Sex steroid hormones contribute to this phenomenon. In particular, 5α-androstane-3α,17β-diol (3α-diol) is a testosterone metabolite that has demonstrated neuroprotection against oxidative stress. The ability of 3α-diol to protect against physiological stress has not been explored. The experiments in this thesis explore molecular responses to glucocorticoids in male and female hippocampus, and the potential for 3α-diol to circumvent these responses. This thesis demonstrates that male and female mHippoE cells are glucocorticoid responsive. Furthermore, glucocorticoids downregulate dual specificity phosphatase 6 (DUSP6) in mHippoE cells. 3α-diol rescues the DUSP6 response to glucocorticoids in male mHippoE cells only. Correspondingly, DUSP6 is downregulated by restraint stress in females only. Collectively, the findings in this thesis are consistent with the hypothesis that 3α-diol is protective against the effects of glucocorticoids in a sex-specific manner.
URI: https://hdl.handle.net/10214/26475
Date: 2021-09
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