Human Factors and Behavioral Neurobiology
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, 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 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-1, IL-6, TNF-) expression. IV-infected IV) animals treated daily with 15mg/kg body weight. DHEA-S treatment reduced inflammatory gene transcripts (IL-1, TNF-, CD3, GFAP) in brain compared to vehicle-(-cyclodextrin)-treated FIV animals similar to levels found in vehicle treated FIV animals. DHEA-S treatment also increased CD4T-cell levels and prevented neurobehavioral deficits and neuronal loss among FIV animals, compared to vehicle-treated FIV animals. Reduced neuronal neuro-steroid synthesis was evident in lentivirus infections, but treatment with DHEA-S limited neuroinflammation and prevented neurobehavioral deficits. Neurosteroid-derived therapies could be effective in the treatment of virus- or inflammation-mediated neurodegeneration.
The FASEB Journal
John Wiley & Sons, Ltd
Scholarly Commons Citation
Paul, A., Maingat, F. G., Polyak, M. J., Vivithanaporn, P., Noorbakhsh, F., Ahboucha, S., Baker, G. B., Pearson, K., & Power, C. (2012). Neurosteroid-Mediated Regulation of Brain Innate Immunity in HIV/Aids: DHEA-S Suppresses Neurovirulence. The FASEB Journal, 27(2). https://doi.org/10.1096/fj.12-215079
Behavioral Neurobiology Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Immunology of Infectious Disease Commons, Medical Immunology Commons, Neurology Commons, Virology Commons, Virus Diseases Commons