50-75% of HIV-infected adults are affected with some degree of neurological problems, and 20% develop AIDS dementia. This injury occurs in the absence of opportunistic infections or metastasis and a hallmark is neuronal loss. Alcohol and HIV infection have been shown to produce similar neuropathological profiles, including frontal neuronal loss. There is evidence in the literature that chronic alcohol consumption potentiates AIDS-related neuropathy. HIV-positive patients with long-term (not short- term) substance abuse, including alcohol, are more likely to have greater neurologic disability. In addition, alcohol abuse and HIV infection have at least additive effects on abnormal brain electrophysiological measurements and alcohol abuse results in earlier abnormalities in the HIV disease process. Also, the adverse metabolic effects of HIV on the brain (as judged by cerebral phosphorous metabolites) are augmented by chronic ethanol abuse. However, the effects of alcohol on AIDS-related neuronal dysfunction have not been tested experimentally. We propose to investigate alcohol potentiation of AIDS neuropathy, by studying both the development of alcohol-increased neuropathy in an animal model (the SIV model in rhesus monkey) and the cellular mechanism of ethanol-increased injury from HIV viral proteins. These are our Specific Aims:
Specific Aim I : Test the hypothesis that Alcohol Enhances Neuropathology in the SIV Rhesus Monkey Model. We will monitor the development of cognitive/motor dysfunction in SIV-infected monkeys with and without chronic alcohol administration, and examine postmortem brain for signs of alcohol-enhanced injury.
Specific Aim II : Test the hypothesis that Ethanol Enhances HIV Neuropathy by Increased Inflammatory Injury and Excitotoxicity. By using an in vitro cultured neuronal cell model, we will determine the involvement of oxidative stress, excitotoxicity, inflammatory mediator formation, and compromised astrocytic neurotrophic activity on the effects of ethanol on neuronal injury induced by HIV viral coat proteins.
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