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

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.