The effect of continuous treatment with 5α androstane-3α, 17-β diol (3α-diol) on protein markers in the triple transgenic mouse model of Alzheimer’s Disease

Bhullar, Simran
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University of Guelph

Age-related decrease in the levels of testosterone has been associated with an increased risk of developing Alzheimer’s Disease (AD). Supplementation with testosterone and dihydrotestosterone has been shown to improve AD-related neuropathology. Recently, their metabolite 5α-androstane-3α,17β-diol (3α-diol) has also shown to improve cognitive dysfunction in rodent models, and attenuate dysregulated extracellular signal-regulated kinase phosphorylation associated with β amyloid neurotoxicity in vitro. The role of continuous treatment with 3α-diol in an AD-animal model remains largely understudied. This thesis investigated the effect of continuous 3α-diol treatment on ERK and its phosphatase DUSP6, on protein markers associated with AD, and on astroglial and microglial markers in 6- and 9-month 3xTg-AD and wild-type male and female mice. No direct treatment effect of 3α-diol was seen, although multiple significant interactions were reported for certain markers. For the first time, the results present in the thesis provide evidence of the impact of 3α-diol supplementation on molecular markers associated with AD.

Alzheimer's Disease, steroid hormones, 5α androstane-3α, 17-β diol, 3α-diol, neuroinflammation, testosterone metabolite