Effects of Chronic Restraint Stress on Aromatase, Estrogen Receptors, Inflammatory Markers and Local Estrogen Production in Brain
Year: 2019
Type: dissertation
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.
Author: Di Rao
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2940142904