ALCOHOL-MEMBRANE INTERACTION ON THE BRAIN: AGING EFFECT

酒精与大脑膜的相互作用：衰老效应

• 批准号: 3108778
• 负责人: ALBERT Y SUN
• 金额: $ 13.44万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3108778
• 关键词: acylation; acyltransferase; affinity labeling; aging; alcoholic beverage consumption; alcoholism /alcohol abuse; animal age group; brain cell; brain metabolism; cell membrane; cholesterol; density gradient ultracentrifugation; drug tolerance; drug withdrawal; electron spin resonance spectroscopy; ethanol; fluorescence polarization; free fatty acids; gel electrophoresis; lysophospholipids; membrane lipids; membrane permeability; membrane structure; neurotransmitter metabolism; pathogenic diet; phosphoglycerides; physical chemical interaction; radiotracer; synaptosomes; tissue /cell culture

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.

虽然酗酒和酗酒被认为是重要的健康 老年人的问题，很少有人知道的病理生理 长期摄入乙醇的后果。 主要 这项研究的目的是检验酒精和 衰老会导致脑细胞膜的退化， 加速大脑老化过程并改变神经膜的完整性， 从膜物理性质，脂质组成， 转运酶和神经递质摄取和释放系统。 实验旨在评估酒精和衰老对 脑突触膜的结构和功能。 具体而言是 急性和慢性乙醇给药对各种生物物理 将在C57 BL/6 NNIA小鼠中检查生化参数， 不同年龄段的人。 这些参数将与 急性乙醇中毒的行为反应和 不同年龄组的耐受性和身体依赖性。 我们还将 比较来自不同年龄组的小鼠从 慢性酒精治疗 对于急性乙醇研究， AGES将通过胃内或腹膜内注射给予乙醇。 为 在慢性研究中，小鼠将成对喂食含有以下成分的Bioserv液体饮食： 5%（w/v）乙醇或Bioserv对照饲料。 容忍度的发展， 不同年龄组将通过他们的睡眠时间和体温过低来评估。 乙醇（3.0g/kg）刺激后的反应。 突触体和 突触质膜将被分离用于各种生物物理学和生物化学， 生物化学研究：（1）膜物理性质的检查 （通过ESR和荧光偏振的流动性），（2）膜的分析 脂质成分（酸性磷脂和胆固醇），（3） 神经递质摄取和释放过程的测量，和（4）测定 膜结合酶，如（Na+K）-ATP酶，乙酰胆碱酯酶和 5 '-核苷酸酶。 此外，分离的突触膜的反应 从对照和乙醇耐受小鼠向体外激发 乙醇和不同碳链长度的脂肪醇将被 在不同年龄组的小鼠中进行评估。 预计该 调查结果将有助于进一步了解 大脑中的酒精-膜相互作用，并提供更深入的了解 酒精在衰老过程中的作用。 最终目标是 为酒精引起的损害提供适当和有效的治疗 以及中枢神经系统的相关疾病。