HIV-1, Methamphetamine and Astrocyte Glutamate Regulation: Combined Excitotoxic Implications for Neuro-AIDS

摘要: Glutamate, the most abundant excitatory transmitter in brain can lead to neurotoxicity when not properly regulated. Excitotoxicity is a direct result of abnormal regulation glutamate concentrations synapse, and common neurotoxic mediator associated with neurodegenerative disorders. It well accepted that methamphetamine (METH), potent central nervous stimulant high abuse potential, human immunodeficiency virus (HIV)-1 are implicated progression neurocognitive malfunction. Both have been shown induce effects such as astrogliosis, compromised blood barrier integrity, excitotoxicity brain. Reduced uptake from neuronal synapses likely leads accumulation extracellular spaces. Astrocytes express transporters responsible for majority vesicular release. However, cellular molecular mechanisms astrocyte-mediated context METH HIV-1 undefined. Topics reviewed include dysregulation transporters, specifically amino acid transporter-2, metabotropic receptor(s) expression release by exocytosis. We also discuss concentration through astrocytic enzymes synthesis metabolism. Lastly, we recent evidence various astrocyte neuron crosstalk regulation. play an essential role neuropathologies METH/HIV-1-induced excitotoxicity. hope shed light on pathways astrocytes share during drug infection.