ALCOHOL-MEMBRANE INTERACTION IN THE BRAIN--AGING EFFECT

有一个普遍的共识，自由基的产生导致 细胞膜的生物化学和生物物理性质的改变 反过来，这些变化可能导致病理表现， 衰老和退行性疾病。 我们实验室的最新数据显示， 表明促氧化剂可能参与了 神经退行性疾病，乙醇可能会加强这些 通过参与自由基反应来进行。 的 该项目的总体目标是评估假设， 加速老化过程和神经元功能丧失， 饮酒与自由基反应增强有关 乙醇。 由于谷氨酸受体的激活已被证明 会导致痴呆和严重的记忆障碍， 老化，我们将使用谷氨酸和其他促氧化剂（如螯合 铁和H2 O2）作为实验工具，以检查乙醇对 神经退化过程 这项建议的具体目标是： (1)来验证乙醇增强自由基的假设 神经退行性变过程的机制;（2）研究神经退行性变的机制， 参与氧化损伤的老化过程，并研究如何 酒精通过参与自由基反应影响衰老 和（3）研究可能的饮食和药物干预， 谷氨酸盐和其他促氧化剂引起酒精相关损伤 压力源 乙醇对促氧化剂诱导的细胞死亡和凋亡的影响 将在PC-12细胞和C57 BI/6 NNIA小鼠中检查组织损伤， 分别 氧化损伤将通过测定细胞 活性，硫代巴比妥酸反应物质（TBARS）的形成， 乳酸脱氢酶（LDH）释放、膜脂质组成和 膜酶的活性和摄取过程（例如Na-泵， 儿茶酚胺摄取等）。 此外，抗氧化剂的能力 (such维生素E和C）和药物（钙阻滞剂，水杨酸盐）， 保护免受乙醇引起的氧化损伤也将是 研究了 预计通过这次调查， 膜劣化机制的重要信息， 大脑由于老化和/或酒精摄入可以获得和预防 可以提出防止这些变化的措施。

There is a general consensus that free radical generation leads to alterations of biochemical and biophysical properties of cell membranes and in turn, these changes may lead to pathological manifestations in aging and in degenerative diseases. Recent data from our laboratory has indicated that pro-oxidant agents may be involved in the pathogenesis of neurodegenerative diseases and that ethanol may potentiate these processes through participating in the free radical reaction. The overall objective of this project is to evaluate the hypothesis that the accelerated aging process and loss of neuronal function associated with alcohol drinking is related to the enhancement of free radical reaction by ethanol. Since activation of the glutamate receptor has been shown to cause global dementia and severe memory impairment similar to that in aging, we will use glutamate and other pro-oxidants (such as chelated iron and H2O2) as experimental tools to examine the effects of ethanol on the neurodegenerative processes. The specific aims of this proposal are: (1) to test the hypothesis that ethanol potentiates the free radical mechanism of neurodegenerative process; (2) to investigate the involvement of oxidative insults on the aging process, and to examine how alcohol affects aging through participation in the free radical reactions and (3) to investigate possible dietary and drug interventions against the alcohol-related damage as caused by glutamate and other pro-oxidant stressors. The effects of ethanol on pro-oxidant-induced cell death and tissue damage will be examined in PC-12 cells and in C57BI/6NNIA mice, respectively. Oxidative damage will be assessed by determining cell viability, formation of thiobarbituric acid reactive substances (TBARS), lactic acid dehydrogenase (LDH) release, membrane lipid composition and activity of membrane enzymes and uptake processes (e.g. Na-pump, catecholamine uptake, etc). In addition, the ability of antioxidants (such as vitamins E and C), and drugs (Ca2+-blockers, salicylate) to protect against oxidative damage elicited by ethanol will also be investigated. It is anticipated that through this investigation, important information on the mechanism of membrane deterioration in the brain due to aging and/or alcohol intake may be obtained and preventive measures for protecting against these changes may be proposed.