ALCOHOL POTENTIATION OF AIDS RELATED NEUROPATHY

50-75%的艾滋病毒感染成年人受到某种程度的影响， 神经系统问题，20%发展成艾滋病痴呆。这种伤害发生在 在没有机会性感染或转移的情况下， 神经元缺失 酒精和艾滋病毒感染已被证明产生类似的 神经病理学特征，包括额叶神经元损失。有 文献中的证据表明，长期饮酒 艾滋病相关神经病变。长期（而非短期）感染艾滋病毒的患者 包括酒精在内的药物滥用者， 神经系统残疾此外，酗酒和艾滋病毒感染 至少对异常脑电生理学的叠加效应 测量和酒精滥用导致早期异常的艾滋病毒 疾病过程。此外，艾滋病病毒对大脑的不良代谢影响 (as根据脑磷代谢物判断）， 乙醇滥用然而，酒精对艾滋病相关神经元的影响 功能障碍还没有经过实验测试。 我们建议调查酒精增强艾滋病神经病变， 研究酒精增加的动物神经病变的发展， 模型（恒河猴SIV模型）和细胞机制， 乙醇增加了HIV病毒蛋白的损伤。这些是我们的具体 目的： 具体目标I：检验酒精增强神经病理学的假设 SIV恒河猴模型我们会密切留意 SIV感染猴的认知/运动功能障碍， 长期酒精管理，并检查死后大脑的迹象， 酒精强化的损伤 具体目标II：检验乙醇增强HIV神经病变的假设 炎症性损伤和兴奋性毒性增加。通过使用体外 培养的神经元细胞模型，我们将确定参与 氧化应激、兴奋性毒性、炎症介质形成，以及 受损的星形胶质细胞神经营养活性对乙醇 HIV病毒外壳蛋白诱导的神经元损伤。

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.