ETHANOL CONSUMPTION AND LIVER AND BRAIN METABOLISM

乙醇消耗与肝脏和大脑的代谢

• 批准号: 6168161
• 负责人: CAROL C CUNNINGHAM
• 金额: $ 9.96万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6168161
• 关键词: adenosine triphosphate; alcoholic beverage consumption; alcoholic liver cirrhosis; brain metabolism; disease /disorder model; dopamine; ethanol; gamma aminobutyrate; glucose metabolism; glycolysis; laboratory rat; liver function; liver metabolism; mitochondria; neurotransmitter metabolism; norepinephrine; nuclear magnetic resonance spectroscopy; oxidative phosphorylation; oxidative stress; polymerase chain reaction; self medication; serotonin

The basis for ethanol-related alterations in the organism is intimately linked to the metabolism of ethanol and the changes ethanol elicits in normal metabolic pathways. While this principle is applicable in all organs affected by ethanol, the response in different tissues can vary widely. Thus, a study of the metabolism associated with ethanol can be focused on different responses in different organs. The studies encompassed in this application for a Senior Scientist award are directed toward the effects of ethanol on metabolic systems in liver and brain. With regard to the liver studies, the major goal is to relate alterations in metabolism to development of alcoholic liver disease. Included are studies of the effects of ethanol on 1) the integrity of the mitochondrial oxidative phosphorylation system and 2) the synthesis of ATP via the glycolytic pathway. Experiments are included to examine how ethanol-elicited alterations in the above mechanisms affect the structural and functional integrity of the hepatocyte. The interplay between oxidative stress and cellular energy state in the ethanol- related loss of hepatocyte viability will also be evaluated. The metabolic studies in the brain, which are a new area for me, are focused on establishing alterations in glucose and neurotransmitter metabolism that accompany the behavioral changes occurring when an individual self-administers ethanol. The synthetic pathways for the amino acid and biogenic amine neurotransmitters will be investigated in a rodent self-administration model. The purpose for the Senior Scientist application is to obtain enough research time to allow me to add the neurotransmitter metabolism study while I maintain current effort on my liver-ethanol program.

生物体中乙醇相关改变的基础与 与乙醇代谢和乙醇释放的变化有关， 正常的代谢途径。 虽然这一原则适用于所有 受乙醇影响的器官，不同组织的反应可能不同 广泛地。 因此，与乙醇相关的代谢研究可以 关注不同器官的不同反应。 研究 本高级科学家奖申请书包括 针对乙醇对肝脏代谢系统的影响， 个脑袋 关于肝脏研究，主要目标是 代谢的改变与酒精性肝病的发展有关。 包括乙醇对以下方面影响的研究：1） 线粒体氧化磷酸化系统和2）合成 通过糖酵解途径释放ATP。实验包括检查 乙醇引起的上述机制的改变如何影响 肝细胞的结构和功能完整性。 的相互作用 氧化应激和细胞能量状态之间的关系， 还将评价肝细胞活力的相关损失。 大脑的代谢研究对我来说是一个新领域， 专注于建立葡萄糖和神经递质的改变 新陈代谢伴随着行为变化发生时， 个人自行服用乙醇。 的合成途径 氨基酸和生物胺神经递质将在 啮齿动物自我给药模型。 老年人的目的 科学家申请是为了获得足够的研究时间，让我 加上神经递质代谢研究，同时我保持最新的 我的肝脏乙醇项目