BRAIN GLUCOSE METABOLISM BY 13C NMR

通过 13C NMR 测定脑葡萄糖代谢

基本信息

批准号：
2903352
负责人：
CAROL C CUNNINGHAM
金额：
$ 0.87万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-04-01 至 2000-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2903352
关键词：
aspartate brain metabolism carbon diagnosis design /evaluation ethanol gamma aminobutyrate glucose metabolism glutamates laboratory rat method development neurotransmitter biosynthesis neurotransmitter metabolism noninvasive diagnosis nuclear magnetic resonance spectroscopy tissue /cell culture

项目摘要

APPLICANT'S ABSTRACT: The effects of ethanol on the glutamate and gamma amino butyric acid (GABA) neurotransmitter systems, and behavioral responses involving these systems, are well established. Less is known of the influence of ethanol on the rates of synthesis of the amino acid neurotransmitters. The overall Objective of this project is to develop techniques that will allow us to measure the effects of ethanol administration on the rates of synthesis of the neurotransmitters, glutamate, GABA and aspartate, from glucose in the intact, conscious rat. The rates of neurotransmitter synthesis and patterns of glucose metabolism will be determined using "C NMR spectroscopy to analyze for the distribution of isotope into glucose metabolites. This technique allows for a quantitative evaluation of glucose incorporation into metabolites, including the neurotransmitters, by identifying the distribution of "C into particular carbon atoms within a metabolite. A long range goal is to determine the impact of ethanol on the metabolism of glucose through the glycolytic, anaplerotic and oxidative pathways in order to relate alterations in glucose metabolism to changes in the rates of neurotransmitter synthesis. Studies will be carried out utilizing a dose of ethanol which stimulates motor activity (0.25 g/kg body weight) and one which has a -sedative effect on the organism (1.0 g/kg body weight). It is expected that these two doses will influence the patterns of glucose metabolism and neurotransmitter synthesis differently since it has been previously demonstrated that they exert opposite effects on the uptake of glucose in certain brain regions. Techniques will also be developed to study the effects of ethanol on glucose and neurotransmitter metabolism in mixtures of isolated astrocytes and neurons (co-cultures). Once this latter technology is established, it will be utilized in future studies to differentiate between direct and indirect effects of ethanol on glucose and neurotransmitter metabolism in the brain, particularly in the cerebral cortex. 1:3C NMR spectroscopy will also be utilized in development of the techniques for following glucose and neurotransmitter metabolism in the co-cultures.

申请人的摘要：乙醇对谷氨酸和伽玛的影响氨基丁酸（GABA）神经递质系统和行为反应涉及这些系统，已经建立了良好。少知道乙醇对氨基酸合成速率的影响神经递质。该项目的总体目的是开发将使我们能够测量乙醇的影响的技术施用神经递质的合成速率，谷氨酸，GABA和天冬氨酸，来自完整，有意识的大鼠的葡萄糖。神经递质合成的速率和葡萄糖代谢的模式将使用“ C NMR光谱法来分析分布同位素成葡萄糖代谢产物。该技术允许将葡萄糖掺入代谢物的定量评估，包括神经递质，通过识别“ C到特定的分布代谢产物内的碳原子。一个远距离目标是确定乙醇对葡萄糖代谢的影响，通过糖酵解，为了关联葡萄糖的改变，变性和氧化途径神经递质合成速率变化的代谢。研究将使用刺激运动的乙醇剂量进行活性（0.25 g/kg体重），一种对有机体（1.0 g/kg体重）。预计这两种剂量会影响葡萄糖代谢和神经递质合成的模式自从以前证明它们发挥作用以来，以不同的方式对某些大脑区域葡萄糖摄取的影响相反。还将开发技术来研究乙醇对葡萄糖的影响孤立星形胶质细胞混合物中的神经递质代谢和神经递质代谢神经元（共培养）。一旦建立了后一种技术，它将在以后的研究中使用以区分直接和间接乙醇对大脑中葡萄糖和神经递质代谢的影响，特别是在大脑皮层中。 1：3C NMR光谱也将是用于遵循葡萄糖和的技术开发共培养中的神经递质代谢。