5α-reduced progestogens ameliorate mood-related behavioral pathology, neurotoxicity, and microgliosis associated with exposure to HIV-1 Tat

Brain, Behavior, and Immunity
Jason J ParisKurt F Hauser

Abstract

Human immunodeficiency virus (HIV) is associated with motor and mood disorders, likely influenced by reactive microgliosis and subsequent neural damage. We have recapitulated aspects of this pathology in mice that conditionally express the neurotoxic HIV-1 regulatory protein, trans-activator of transcription (Tat). Progestogens may attenuate Tat-related behavioral impairments and reduce neurotoxicity in vitro, perhaps via progesterone's 5α-reductase-dependent metabolism to the neuroprotective steroid, allopregnanolone. To test this, ovariectomized female mice that conditionally expressed (or did not express) central HIV-1 Tat were administered vehicle or progesterone (4mg/kg), with or without pretreatment of a 5α-reductase inhibitor (finasteride, 50mg/kg). Tat induction significantly increased anxiety-like behavior in an open field, elevated plus maze and a marble burying task concomitant with elevated protein oxidation in striatum. Progesterone administration attenuated anxiety-like effects in the open field and elevated plus maze, but not in conjunction with finasteride pretreatment. Progesterone also attenuated Tat-promoted protein oxidation in striatum, independent of finasteride pretreatment. Concurrent experiments in vitr...Continue Reading

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Citations

Mar 16, 2016·Brain, Behavior, and Immunity·F Rohan Walker, Raz Yirmiya
Aug 3, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Ian R JacobsSylvia Fitting
Jul 1, 2021·Journal of Neuroendocrinology·Silvia DiviccaroRoberto Cosimo Melcangi
Aug 29, 2021·Pharmaceuticals·Vitor H PominJason J Paris
Oct 16, 2021·Journal of Neuroendocrinology·Mohammed F SalahuddinJason J Paris

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