ETHANOL CONSUMPTION AND LIVER AND BRAIN METABOLISM

乙醇消耗与肝脏和大脑的代谢

• 批准号: 6629530
• 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/6629530
• 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.

生物体中与乙醇相关的改变的基础是密切的 与乙醇的代谢以及乙醇引起的变化有关 正常的代谢途径。 虽然该原则适用于所有 受乙醇影响的器官，不同组织中的反应可能会有所不同 广泛。 因此，对与乙醇相关的代谢的研究可能是 专注于不同器官的不同反应。 研究 该申请中的高级科学家奖是 针对乙醇对肝脏代谢系统的影响 脑。 关于肝脏研究，主要目标是联系 代谢对酒精性肝病发展的改变。 包括乙醇对1）完整性的研究 线粒体氧化磷酸化系统和2）合成 ATP通过糖酵解途径。包括实验以检查 上述机制中乙醇引起的变化如何影响 肝细胞的结构和功能完整性。 相互作用 在乙醇中的氧化应激和细胞能态之间 还将评估肝细胞生存力的相关损失。 对我来说，大脑的代谢研究是 专注于建立葡萄糖和神经递质的改变 行为改变伴随的代谢 个体自我辅助乙醇。 的合成途径 将研究氨基酸和生物胺神经递质 啮齿动物自我管理模型。 高年级的目的 科学家的应用是要获得足够的研究时间，以使我能够 在保持电流时，添加神经递质代谢研究 在我的肝乙醇计划上努力。