BRAIN GLUCOSE METABOLISM BY 13C NMR

申请者摘要：乙醇对谷氨酸和伽马的影响 氨基丁酸(GABA)神经递质系统和行为反应 涉及到这些系统，都是很成熟的。鲜为人知的是 乙醇对氨基酸合成速率的影响 神经递质。该项目的总体目标是开发 使我们能够测量乙醇的影响的技术 对神经递质合成速率的影响， 谷氨酸，氨基丁酸和天冬氨酸，从葡萄糖，在完整的清醒大鼠。 神经递质合成速率与糖代谢模式 将测定的碳核磁共振波谱用于分析其分布 将同位素转化为葡萄糖代谢物。这项技术允许 葡萄糖掺入代谢物的定量评估，包括 神经递质，通过确定“C”的分布。 代谢物中的碳原子。一个长期目标是确定 乙醇通过糖酵解对葡萄糖代谢的影响， 抗衰老和氧化途径与血糖变化相关 代谢与神经递质合成速率的变化有关。研究 将使用一定剂量的乙醇来刺激运动 活动(0.25克/千克体重)和一种对人体有镇静作用的 生物体(1.0g/kg体重)。预计这两剂将 影响糖代谢和神经递质合成的模式 不同的是，因为以前已经证明，他们会 对大脑某些区域的葡萄糖摄取有相反的影响。 还将开发技术来研究乙醇对葡萄糖的影响。 和神经递质在分离的星形胶质细胞和 神经元(共培养)。一旦后一种技术建立起来，它将 在未来的研究中用于区分直接和间接 酒精对大脑葡萄糖和神经递质代谢的影响 尤其是在大脑皮层。1：3C核磁共振波谱也将 用于开发跟踪葡萄糖和 共培养体系中的神经递质代谢。

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.