Methamphetamine and HIV-1-induced neurotoxicity: Role of trace amine associated receptor 1 cAMP signaling in astrocytes

摘要: Abstract Methamphetamine (METH) is abused by about 5% of the United States population with approximately 10–15% human immunodeficiency virus-1 (HIV-1) patients reporting its use. METH abuse accelerates onset and severity HIV-associated neurocognitive disorders (HAND) astrocyte-induced neurotoxicity. activates G-protein coupled receptors such as trace amine associated receptor 1 (TAAR1) increasing intracellular cyclic adenosine monophosphate (cAMP) levels in presynaptic cells monoaminergic systems. In present study, we investigated effects HIV-1 on primary astrocyte TAAR1 expression, function glutamate clearance. Our results demonstrate combined conditions increased mRNA 7-fold cAMP levels. beta-phenylethylamine (β-PEA), known agonists, astrocytes. Further, knockdown significantly reduced response to METH/β-PEA, indicating signaling through TAAR1. METH ± HIV-1 decreased excitatory amino acid transporter-2 (EAAT-2) RNA interference for prevented METH-mediated decreases EAAT-2. clearance, which was further heightened METH. Moreover, overexpression EAAT-2 clearance that were Taken together, our data show treatment activated leading astrocytes modulated abilities. Furthermore, molecular alterations correspond changes function. To knowledge this first report implicating a novel during injury context HAND.