Effects of 5alpha-androstane-3alpha,17beta-diol (3alpha diol) on Attention and Cortical Dendritic Morphology in the 3xTg Mouse Model of Alzheimer’s Disease
Neurosteroids promote neural cell survival, but their levels are significantly reduced in neurodegenerative diseases, including Alzheimer’s disease (AD). Recent work has suggested the androgen-derived, 5α-reduced metabolite 3α-diol may specifically contribute to this neuroprotection, as well as to sex differences in AD, although its mechanisms remain largely uncharacterized. Finasteride, a 5α-reductase inhibitor, has been associated with multiple long-lasting, adverse effects. As 5α-reduced metabolites may be critical in regulating neuroprotective effects of circulating steroids in the brain, the studies presented investigate the role of 3α-diol in AD pathology and importance of 5α-reduced metabolites in cognition and emotionality. We assessed long-term 3α-diol and finasteride treatment, respectively, observing alterations in task acquisition, decisional speed, impulsivity, and dendritic branching and length, as well as differential effects in the sexes. This research develops greater insight into the neurobiological basis of AD and aging, and advances the understanding of sex differences, with respect to 5α-reduced metabolites.