ALCOHOL-MEMBRANE INTERACTION IN THE BRAIN--AGING EFFECT

人们普遍认为，自由基的产生会导致 细胞膜生化和生物物理性质的变化 而反过来，这些变化可能会导致 衰老和退行性疾病。我们实验室的最新数据显示 提示促氧化剂可能参与了糖尿病的发病机制。 神经退行性疾病和乙醇可能会加剧这些 通过参与自由基反应来进行。这个 该项目的总体目标是评估以下假设 加速衰老过程和神经元功能丧失与 饮酒与增强自由基反应有关 用乙醇。因为谷氨酸受体的激活已经被证明是 导致全球痴呆症和严重的记忆障碍，类似于 老化时，我们会使用谷氨酸和其他促氧化剂(如螯合物 铁和过氧化氢)作为实验工具来研究乙醇对 神经退化过程。这项建议的具体目标是： (1)检验乙醇增强自由基的假说 神经退行性变过程的机制；(2)研究 氧化侮辱在衰老过程中的参与，并研究如何 酒精通过参与自由基反应影响衰老 以及(3)调查可能的饮食和药物干预措施 谷氨酸和其他促氧化剂引起的酒精相关损害 压力源。乙醇对促氧化剂诱导的细胞死亡的影响及机制 组织损伤将在PC-12细胞和C57BI/6NNIA小鼠中进行检测， 分别进行了分析。氧化损伤的评估将通过检测细胞 活性，硫代巴比妥酸活性物质(TBARS)的形成， 乳酸脱氢酶(LDH)释放、膜脂组成和 膜酶活性和摄取过程(例如，钠泵、 儿茶酚胺摄取等)。此外，抗氧化剂的能力 (如维生素E和C)和药物(钙离子阻滞剂、水杨酸盐) 防止乙醇引起的氧化损伤也将是 调查过了。预计通过此次调查， 膜劣化机理的重要信息 脑部因衰老和/或饮酒可获得并预防 可能会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.