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dc.contributor.authorFerdinand G. Maingaten_US
dc.contributor.authorMaria J. Polyaken_US
dc.contributor.authorAmber M. Paulen_US
dc.contributor.authorPornpun Vivithanapornen_US
dc.contributor.authorFarshid Noorbakhshen_US
dc.contributor.authorSamir Ahbouchaen_US
dc.contributor.authorGlen B. Bakeren_US
dc.contributor.authorKeir Pearsonen_US
dc.contributor.authorChristopher Poweren_US
dc.contributor.otherUniversity of Albertaen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherUniversite Cadi Ayyaden_US
dc.identifier.citationFASEB Journal. Vol.27, No.2 (2013), 725-737en_US
dc.description.abstractNeurosteroids 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 neurosteroidmediated 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, CD3+, GFAP) in brain compared to vehicle-(β-cyclodextrin)-treated FIV+ animals similar to levels found in vehicle-treated FIV+ animals. DHEA-S treatment also increased CD4+ T-cell levels and prevented neurobehavioral deficits and neuronal loss among FIV+ animals, compared to vehicle-treated FIV+ animals. Reduced neuronal neurosteroid synthesis was evident in lentivirus infections, but treatment with DHEA-S limited neuroinflammation and prevented neurobehavioral deficits. Neurosteroidderived therapies could be effective in the treatment of virus-or inflammation-mediated neurodegeneration. © FASEB.en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleNeurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S suppresses neurovirulenceen_US
Appears in Collections:Scopus 2011-2015

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