RAO, DI
(2019)
Effects of Chronic Restraint Stress on Aromatase, Estrogen Receptors, Inflammatory Markers and Local Estrogen Production in Brain.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Our goal is to identify factors that underlie sex dimorphisms in the risk of developing psychological disorders. Numerous studies demonstrate that stress is an important contributing factor. Chronic stress can induce an inflammatory response in the brain, presumably via the activation of microglial cells. Microglial cells are macrophage-like cells in the CNS and are the primary cells responsible for brain immune responses. Glucocorticoids have been reported to stimulate microglia to transform to a pro-inflammatory state and, hence, may be a primary mediator of microglial response to stress. There is evidence that microglia can respond to estrogens which may contribute to different responses in men vs. women. Specifically, estrogens have been shown to inhibit the microglial inflammatory response. Brain levels of estrogens are also determined by local conversion of androgens via the enzyme aromatase. Brain levels of aromatase are higher in males than in females which can result in higher local levels of estradiol in regions of the male brain than in the female brain. Here, we hypothesize that chronically elevated stress hormone (i.e., corticosterone), can influence the activity of aromatase in the brain in a sexually dimorphic way, affecting local levels of estrogens in specific brain regions and resulting in sex differences in microglial activation and neuroinflammatory response. We first did a pilot study focusing on the effects of chronic restraint stress on aromatase in the brain in a sexually dimorphic way, affecting local levels of estrogens in specific brain regions and resulting in sex differences in neuroinflammatory response. We developed a method to detect CORT level in rat serum. Sex differences occurred in serum corticosterone level and CORT levels in female responded more to a stressor than in males. Serum E2 levels were undetectable in males and very low, even undetectable in females. We also detected a pattern suggesting sex differences in the levels of ARO-L, estrogen receptors (ERα, ERβ and GPR30) and inflammatory markers (IL-1ß and TNF-α) mRNA under chronic restraint stress. We did not detect clear changes in local estrogen levels in cerebellum, hippocampus and amygdala. Larger sample size should be applied to further examine the hypothesis.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
4 April 2019 |
| Date Type: |
Publication |
| Defense Date: |
13 March 2019 |
| Approval Date: |
4 April 2019 |
| Submission Date: |
3 April 2019 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
62 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Chronic Restraint Stress; Sex Differences; Rat Brain Inflammatory Responses; Local Estrogen Production; Aromatase |
| Date Deposited: |
04 Apr 2019 16:26 |
| Last Modified: |
04 Apr 2019 16:26 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36240 |
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