ArticleBrain, behavior, and immunity2016
5α-reduced progestogens ameliorate mood-related behavioral pathology, neurotoxicity, and microgliosis associated with exposure to HIV-1 Tat.
Article in Brain, behavior, and immunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Hydrogen Sulfide Rescues Microglia From HIV Tat-Driven Ferroptosis: Implications for HIV-Associated Neuroinflammation.CNS neuroscience & therapeutics · 2026Article
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- HIV-1 Tat Impairment of Mitochondrial Respiration via Complexes I and II Can Be Ameliorated by Allopregnanolone in Opioid-Exposed or Opioid-Naïve Cells and Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation.Communications biology · 2024Article
- HIV-1 Tat and morphine interactions dynamically shift striatal monoamine levels and exploratory behaviors over time.Journal of neurochemistry · 2024Article
- Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation.Research square · 2023Article
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- Myelin regulatory factor is a target of individual and interactive effects of HIV-1 Tat and morphine in the striatum and pre-frontal cortex.Journal of neurovirology · 2023Article
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- Hormonal milieu drives economic demand for cocaine in female rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy.Journal of neuroendocrinology · 2022Review
- In vivo proton magnetic resonance spectroscopy detection of metabolite abnormalities in aged Tat-transgenic mouse brain.GeroScience · 2021Article
- Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat.Pharmaceuticals (Basel, Switzerland) · 2021Article
- HIV-1 Tat and morphine decrease murine inter-male social interactions and associated oxytocin levels in the prefrontal cortex, amygdala, and hypothalamic paraventricular nucleus.Hormones and behavior · 2021Article
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- Mini-review: Elucidating the psychological, physical, and sex-based interactions between HIV infection and stress.Neuroscience letters · 2021Review
- HIV-1 Tat promotes age-related cognitive, anxiety-like, and antinociceptive impairments in female mice that are moderated by aging and endocrine status.GeroScience · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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 vitro revealed Tat (50nM)-mediated reductions in neuronal cell survival over 60h, as well as increased neuronal and microglial intracellular calcium, as assessed via fura-2 AM fluorescence. Co-treatment with allopregnanolone (100nM) attenuated neuronal death in time-lapse imaging and blocked the Tat-induced exacerbation of intracellular calcium in neurons and microglia. Lastly, neuronal-glial co-cultures were labeled for Iba-1 to reveal that Tat increased microglial numbers in vitro and co-treatment with allopregnanolone attenuated this effect. Together, these data support the notion that 5α-reduced pregnane steroids exert protection over the neurotoxic effects of HIV-1 Tat.
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