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Regulation of microRNAs by stress and gonadal hormones in the male and female mouse hippocampus

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Title: Regulation of microRNAs by stress and gonadal hormones in the male and female mouse hippocampus
Author: Creighton, Carolyn Elaine
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: MacLusky, Neil J
Abstract: Hormonal changes have profound effects on the structure and function of the central nervous system. One region that is especially affected by hormonal changes is the hippocampus, a brain region known for its roles in learning and memory. Within the hippocampus, different hormones –gonadal and stress –interact in a sex-dependent fashion to control hippocampal structure and function. While research has explored the role of different receptors and cell signaling pathways in this interaction, the underlying mechanisms are incompletely understood. This thesis begins to explore the possible role of microRNAs (miRNAs) as mediators of gonadal/stress hormone interactions. In non-neural tissues, miRNAs are regulated by hormones and in turn control hormone signaling. In neural tissues, miRNAs are known to regulate important structural processes such as dendritic arborisation. Since these structural changes are also regulated by hormones, miRNAs could be important regulators of the hormone-mediated gene expression that underlie these processes. The first objective of this thesis was to examine the effects of 17β-estradiol on hippocampal miRNA expression in the female mice using small RNA sequencing. Mice were given a single injection of 17β-estradiol, and the rapid effects on miRNA expression examined. Interestingly, this study revealed that even the mild stress associated with handling and injection altered miRNA expression, which could interfere with the effects of estradiol. The initial study was then expanded into the second objective to specifically determine the effect of the stress of handling on miRNA expression, and to examine if changes in expression were similar between males and females. The final objective looked at the direct, rapid effects of modulators of the stress-response system on miRNA expression using an in vitro model system. Specifically the effects of corticotropin-releasing hormone (CRH) and dexamethasone on miR-34c-5p expression in SH-SY5Y neuroblastoma cells were assessed. Together the results presented in this thesis suggest that gonadal and stress hormones may both affect the expression of a subset of miRNAs in the hippocampus.
Date: 2017-01
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