Cerebral Metabolism of Ethanol-Derived Acetate

乙醇衍生的乙酸酯的脑代谢

• 批准号: 7111238
• 负责人: PETER C NICHOLAS
• 金额: $ 3.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111238
• 关键词: acetates; alcoholic beverage consumption; alcoholism /alcohol abuse; aminoacid; astrocytes; behavior test; behavioral /social science research tag; brain metabolism; chemical kinetics; drug addiction; drug withdrawal; ethanol; glucose; glutamates; laboratory rat; liver function; neurochemistry; neurotoxicology; nuclear magnetic resonance spectroscopy; oxidation; predoctoral investigator; radiotracer; serum; substance abuse related behavior

DESCRIPTION (provided by applicant): The focus of this proposal is the cerebral metabolism of acetate derived from ethanol. Acetate is the breakdown product of hepatic ethanol metabolism, and acetate is a substrate for cerebral metabolism in astrocytes. Astrocytes are responsible for removing the excitatory neurotransmitter glutamate from the extracellular space. We hypothesize that metabolic adaptation by astrocytes to use acetate as a substrate may hamper the ability of these cells to clear extracellular glutamate when acetate becomes unavailable during ethanol withdrawal. The initial aim of this proposal will determine the extent to which cerebral metabolism of acetate occurs following ethanol consumption. We will administer Carbon-13 enriched ethanol and analyze trafficking of this tracer into cerebral amino acids by Carbon-13 NMR spectroscopy of serum and extracts of brain and liver. Using similar techniques, we will determine whether cerebral utilization of acetate increases following chronic ethanol exposure. The second aim will determine whether chronic ethanol exposure alters cerebral metabolism of acetate and glucose during withdrawal from ethanol in a manner that could contribute to withdrawal-induced hyperexcitability.

描述（由申请人提供）：该提案的重点是乙醇衍生的乙酸盐的脑代谢。乙酸是肝乙醇代谢的分解产物，乙酸是星形胶质细胞脑代谢的底物。星形胶质细胞负责从细胞外空间去除兴奋性神经递质谷氨酸。我们假设，当乙醇戒断期间乙酸盐变得不可用时，星形胶质细胞对使用乙酸盐作为底物的代谢适应可能会阻碍这些细胞清除细胞外谷氨酸的能力。该提案的最初目的是确定乙醇消耗后大脑中醋酸盐代谢的程度。我们将使用富含碳 13 的乙醇，并通过血清以及脑和肝脏提取物的碳 13 核磁共振波谱分析该示踪剂向脑氨基酸的运输。使用类似的技术，我们将确定长期接触乙醇后大脑对醋酸盐的利用是否会增加。第二个目标将确定长期接触乙醇是否会改变乙醇戒断期间醋酸盐和葡萄糖的大脑代谢，从而导致戒断引起的过度兴奋。