Neurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S suppresses neurovirulence

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Ferdinand MaingatChristopher Power

Abstract

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during lentivirus infections, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid-mediated effects and lentivirus infection outcomes. Analyses of HIV-infected (HIV(+)) and uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV(+) macrophages exhibited suppressed enzyme expression without reduced cellular viability. HIV(+) human macrophages treated with sulfated dehydroepiandrosterone (DHEA-S) showed suppression of inflammatory gene (IL-1β, IL-6, TNF-α) expression. FIV-infected (FIV(+)) animals treated daily with 15 mg/kg body weight. DHEA-S treatment reduced inflammatory gene transcripts (IL-1β, TNF-α, CD3ε, GFAP) in brain compared to vehicle-(β-cyclodextrin)...Continue Reading

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Citations

Feb 3, 2012·The American Journal of Chinese Medicine·Li-Heng PaoPei-Wei Huang
Jun 3, 2014·Retrovirology·John G WalshChristopher Power
Aug 30, 2014·Endocrinology and Metabolism Clinics of North America·George P Chrousos, Evangelia D Zapanti
Jul 31, 2013·Journal of the American Heart Association·Jason V BakerUNKNOWN INSIGHT SMART Study Team
Sep 13, 2017·Frontiers in Neurology·Kald Beshir Tuem, Tesfay Mehari Atey
Nov 17, 2020·Frontiers in Veterinary Science·Gianfranco GabaiLieta Marinelli
Oct 16, 2021·Journal of Neuroendocrinology·Mohammed F SalahuddinJason J Paris

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