5α-Reduced Progestogens Ameliorate Mood-Related Behavioral Pathology, Neurotoxicity, and Microgliosis Associated with Exposure to HIV-1 Tat

The study investigated the effects of 5α-reduced progestogens, specifically progesterone and its metabolite allopregnanolone (AlloP), on mood-related behavioral pathology, neurotoxicity, and microgliosis associated with HIV-1 Tat exposure. Using a transgenic mouse model, researchers found that HIV-1 Tat increased anxiety-like behavior and protein oxidation in the brain of ovariectomized female mice. Administration of progesterone ameliorated these effects, but this protective effect was reduced when the conversion of progesterone to AlloP was blocked. The study suggested that AlloP could mitigate HIV-1 Tat-induced neurodegeneration, microgliosis, and intracellular calcium disturbances in vitro. These findings highlighted the potential of 5α-reduced progestogens in reducing neuroinflammation and neurotoxicity associated with HIV-1 Tat, with implications for understanding sex differences in neuroAIDS pathology.