ALCOHOL-MEMBRANE INTERACTION ON THE BRAIN: AGING EFFECT

尽管酗酒和酗酒被认为是重要的健康 老年人的问题，对其病理生理学知之甚少 在这一人群中长期摄入乙醇的后果。主 这项研究的目的是检验酒精和 衰老会导致脑膜的恶化，而酒精 加速大脑老化过程，改变神经膜的完整性， 从细胞膜的物理性质、脂质成分、 运输酶，以及神经递质摄取和释放系统。 实验旨在评估酒精和衰老对健康的影响 脑突触膜的结构和功能。具体地说， 急、慢性酒精摄入对多种生物物理指标的影响 并对C57BL/6NNIA小鼠进行生化指标检测。 不同的年龄段。这些参数将与 急性酒精中毒的行为反应及其发展 不同年龄段的耐受性和身体依赖性。我们还将 比较不同年龄段的小鼠的恢复情况 慢性乙醇治疗。对于急性酒精研究，不同类型的小鼠 AGEs将给予乙醇灌胃或ip。注射。为 慢性研究，小鼠将被配对喂养含有Bioserv的液体饮食 5%(w/v)乙醇或Bioserv对照饲料。容忍度是在 不同年龄段的人将根据他们的睡眠时间和体温过低进行评估 刺激剂量乙醇(3.0g/kg)后的反应。突触体和 将分离突触质膜以用于各种生物物理和 生化研究：(1)膜物理性质的检测 (2)膜的分析 脂类成分(酸性磷脂和胆固醇)，(3) 神经递质摄取和释放过程的测定，以及(4)测定 膜结合酶，如(Na+K)-ATPase、乙酰胆碱酯酶和 5‘-核苷酸酶。此外，分离的突触膜的反应 从对照组和乙醇耐受小鼠到体外挑战 不同碳链长度的乙醇和脂肪醇将 在不同年龄组的小鼠中进行评估。据预计， 这次调查的结果将有助于进一步了解 酒精-膜在大脑中的相互作用，并提供了更好的见解 酒精在衰老过程中的作用。最终目标是 为酒精性损伤提供适当和有效的治疗 以及相关的中枢神经系统疾病。

Although alcoholism and alcohol abuse are recognized as important health problems among the elderly, little is known about the pathophysiological consequences of prolonged ethanol intake in this population. The main objective of this study is to test the hypothesis that both alcohol and aging can cause deterioration of brain membrane and that ethanol accelerates the brain aging process and alters neural membrane integrity, as evident from changes in membrane physical properties, lipid composition, transport enzymes, and neurotransmitter uptake and release systems. Experiments are designed to evaluate the effects of alcohol and aging on structure and functions of brain synaptic membranes. Specifically, the effects of acute and chronic ethanol administration on various biophysical and biochemical parameters will be examined in C57BL/6NNIA mice of different age groups. These parameters will be correlated to the behavioral response to acute ethanol intoxication and development of tolerance and physical dependence among different age groups. We will also compare mice from different age groups with respect to their recovery from chronic ethanol treatment. For acute ethanol studies, mice of different ages will be given ethanol intragastrically or by i.p. injection. For chronic studies, mice will be pair-fed the Bioserv liquid diet containing 5% (w/v) ethanol or the Bioserv control diet. Tolerance developed among different age groups will be assessed by their sleep time and hypothermic response after a challenge dose of ethanol (3.0g/kg). Synaptosomes and synaptic plasma membranes will be isolated for various biophysical and biochemical studies: (1) examination of the membrane physical properties (fluidity by ESR and fluorescence polarization), (2) analysis of membrane lipid composition (the acidic phospholipids and cholesterol), (3) measurement of neurotransmitter uptake and release processes, and (4) assay of membrane-bound enzymes such as (Na+K)-ATPase, acetylcholinesterase and 5'-nucleotidase. In addition, the response of synaptic membranes isolated from control and ethanol-tolerant mice towards in vitro challenge of ethanol and aliphatic alcohols of different carbon chain lengths will be evaluated among mice of different age groups. It is anticipated that the result of this investigation will lead to further understanding of alcohol-membrane interaction in the brain and provide greater insight into the action of alcohol on the aging process. The eventual goal is to provide appropriate and effective treatment for alcohol-induced impairment and related disorders of the central nervous system.