Inhibition of 5α-Reductase Impairs Cognitive Performance, Alters Dendritic Morphology, and Increases Tau Phosphorylation in the Hippocampus of Male 3xTg-AD Mice

    January 2020 in “ Neuroscience ”
    Ari L. Mendell, Samantha D. Creighton, H. R. Wilson, Kristen H. Jardine, Lauren Isaacs, Boyer D. Winters, Neil J. MacLusky
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    TLDR Blocking 5α-reductase can harm memory and brain structure, and increase harmful brain changes in male mice used for Alzheimer's disease research.
    In 2020, a study involving 55 male 3xTg-AD mice, a model for Alzheimer's disease, investigated the effects of inhibiting 5α-reductase, an enzyme involved in testosterone metabolism. The study found that finasteride, a 5α-reductase inhibitor, impaired object recognition memory, increased Tau phosphorylation in the hippocampus, and altered dendritic morphology in these mice. The study also revealed sex-specific differences in dendritic morphology and found that neurosteroids synthesized from progesterone and testosterone may act against the neurotoxic effects of Alzheimer's disease. The results suggest that 5α-reductase may play a crucial role in the neuroprotective effects of circulating steroids on the brain, and its inhibition could potentially contribute to cognitive impairments and neurodegenerative changes associated with Alzheimer's disease.
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