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The Effects of 5α-androstane-3α,17β-diol (3α-diol) Treatment on Neuropathology and Cognitive Dysfunction in the 3xTg Mouse Model of Alzheimer’s Disease

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Title: The Effects of 5α-androstane-3α,17β-diol (3α-diol) Treatment on Neuropathology and Cognitive Dysfunction in the 3xTg Mouse Model of Alzheimer’s Disease
Author: Kuwahara, Nariko
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: MacLusky, Neil
Abstract: Age-related decreases in gonadal steroid hormone levels have been associated with an increased risk of developing Alzheimer’s disease (AD). The incidence of AD is higher in women than men, which may in part reflect the neuroprotective effects of testosterone. Recent in vitro studies have suggested that 5α-reduced neurosteroid metabolites of testosterone, including 5α-androstane-3α,17β-diol (3α-diol), may contribute to these neuroprotective effects and observed sex differences in AD. This thesis investigated whether supplementation with 3α-diol might confer protection against the development of AD in the 3xTg mouse model of AD. 3α-diol treatment improved long-term OR memory in 3xTg-AD males but not females, significantly increased hippocampal dendritic spine density, and differentially altered male and female CA1 dendritic branching and length. The findings presented in this thesis provide novel evidence that 3α-diol treatment exerts sex-specific neuroprotective effects in 3xTg-AD mice.
URI: https://hdl.handle.net/10214/26955
Date: 2022-05
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