ALCOHOL POTENTIATION OF AIDS RELATED NEUROPATHY

50%-75%的艾滋病毒感染者患有不同程度的 神经问题，20%患上艾滋病痴呆症。这种伤害会发生 在没有机会性感染或转移的情况下，标志是 神经元丢失。 酒精和艾滋病毒感染已被证明会产生类似的结果 神经病理特征，包括额叶神经元丢失。的确有 文献中的证据表明长期饮酒会增强 与艾滋病相关的神经病。HIV阳性患者长期(不是短期) 滥用药物，包括酒精，更有可能有更大的 神经性残疾。此外，酗酒和艾滋病毒感染 异常脑电生理的至少相加效应 测量和酗酒导致艾滋病毒早期异常 疾病过程。此外，艾滋病毒对大脑的不利新陈代谢影响 (根据大脑磷代谢产物判断)由慢性疾病引起 酒精滥用。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。 我们建议通过以下方式研究酒精对艾滋病神经病变的增强作用 研究酒精增加的神经病在动物中的发展 模型(恒河猴SIV模型)及其细胞机制 乙醇增加了艾滋病毒病毒蛋白的损伤。这些是我们的具体内容 目标： 具体目标一：检验酒精增强神经病理学的假说 在SIV恒河猴模型中。我们将密切关注 有无SIV感染猴的认知/运动功能障碍 长期饮酒，并检查死后大脑是否有 酒精加重的损伤。 具体目标二：检验酒精可增强艾滋病毒神经病的假设 通过增加炎症损伤和兴奋性毒性。通过使用体外培养的 培养的神经细胞模型，我们将确定是否参与 氧化应激，兴奋性毒性，炎症介质的形成，以及 乙醇对星形胶质细胞神经营养活性的影响 HIV病毒外壳蛋白引起的神经元损伤。

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.