HIV-1 infected mononuclear phagocyte secretory products affect neuronal physiology leading to cellular demise: relevance for HIV-1-associated dementia

Viral and cellular products from HIV-l-infected and/or immune competent mon onuclear phagocytes (MP) (brain macrophages and microglia) affect neuronal function during HIV-l-associated dementia (HAD). Neurotoxic MP factors incl ude, but are not limited to, pro-inflammatory cytokines, chemokines, platel et activating factor, arachidonic acid and its metabolites, nitric oxide, p rogeny virions and viral structural and regulatory proteins. The mechanisms for immune-mediated neural injury in HAD, only now, are being unraveled. I n this regard, we reviewed the current knowledge of how postmitotic neurons , which can neither divide nor be replaced, are damaged by MP secretory act ivities. Linking neuronal function with brain MP activation was made possib le by placing viral and/or immune products onto neurons and measuring cell signaling events or through ex vivo electrophysiological tests on MP-treate d brain slices. Such linkages are shown, in this report, by select demonstr ations of MP factors which cause neuronal dysfunction in HAD.