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Pregnane Steroidogenesis Is Altered By Hiv-1 Tat And Morphine: Physiological Allopregnanolone Is Protective Against Neurotoxic And Psychomotor Effects, Jason Paris, Philippe Lière, Sarah Kim, Fakhri Mahdi, Meagen E. Buchanan, Sara R. Nass, Alaa N. Qrareya, Mohammed F. Salahuddin, Antoine Pianos, Neïké Fernandez, Zia Shariat-Madar, Pamela E. Knapp, Michaël Schumacher, Kurt F. Hauser

Faculty and Student Publications

Pregnane steroids, particularly allopregnanolone (AlloP), are neuroprotective in response to central insult. While unexplored in vivo, AlloP may confer protection against the neurological dysfunction associated with human immunodeficiency virus type 1 (HIV-1). The HIV-1 regulatory protein, trans-activator of transcription (Tat), is neurotoxic and its expression in mice increases anxiety-like behavior; an effect that can be ameliorated by progesterone, but not when 5α-reduction is blocked. Given that Tat's neurotoxic effects involve mitochondrial dysfunction and can be worsened with opioid exposure, we hypothesized that Tat and/or combined morphine would perturb steroidogenesis in mice, promoting neuronal death, and that exogenous AlloP would …