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Studies of brain amino acid metabolism in an animal model of neurological disfunction with ^<13>C-NMR spectroscopy

^ 13 C-NMR波谱研究神经功能障碍动物模型的脑氨基酸代谢

基本信息

批准号：
10680724
负责人：
KANAMATSU Tomoyuki
金额：
$ 1.86万
依托单位：
Institute of Life Science, Soka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Cerebral amino acid metabolism was investigated through the labeling of glutamate, glutamine and GABA from [1-^<13>C] or [2-^<13>C] glucose by ^<13>C-NMR spectroscopy.1) To detect the metabolic fate of ^<13>C-labels entering the brain amino acids through the anaplerotic pathway from [2-^<13>C] glucose, rats were injected intravenously with a bolus of [2-^<13>C] glucose. From this study, it is concluded that the anaplerotic pathway contributes to synthesized glutamate and GABA through the trafficking of glutamine from glia to neuron.2) To know the changes of brain amino acid metabolism, especially metabolic trafficking between neuron and glia, according to the alteration of brain function, rats were injected with [1-^<13>C] glucose 24 hours after treated with repeated electrconvulsive shock (ECS) for 6 days (once a day). The synthesis of glutamine and GABA was decreased by the repeated ECS.However, the synthesis of glutamate was not altered. From these findings it is concluded that rECS decrease the GABA synthesis from glutamate synthesized from glutamine which trafficked from glia to neuron.3) To estimate the cerebral TCA cycle rate and to find the correlation of TCA cycle rate and neuronal function, the non-invasive ^<13>C-MR spectroscopy technique was applied to the anesthetized normal and MPTP induced Parkinson's disease monkey. The TCA cycle rate of normal monkey brain was 0.56 ± 0.058 μmole/g/min, and that value was decreased about 30% in the case of MPTP treatment monkey. From this study, it is thought that the cerebral TCA cycle rate may reflect the neuronal activity.From these three experiments, it may be doubtless that the cerebral amino acid metabolism is intimately associated with brain function. The glutamate synthesis rate indicates the neuronal activity and the glutamine synthesis rate also shows the glial metabolism. Finally we believe that non-invasive measurement of brain amine acid make it possible to diagnosis the brain disorder.

通过^ 13 C-NMR光谱从[1-^ 13 C]或[2-^ 13 C]葡萄糖标记谷氨酸、谷氨酰胺和GABA来研究脑氨基酸代谢。1)检测^ 13 C-标记通过[2-^ 13 C]回补途径进入脑氨基酸的代谢命运。葡萄糖，给大鼠静脉内注射[2-13C]葡萄糖团注。本研究得出回补途径通过将谷氨酰胺从神经胶质细胞运输到神经元来合成谷氨酸和GABA。2)为了了解脑氨基酸代谢的变化，特别是神经元和神经胶质细胞之间的代谢运输的变化，根据脑功能的变化，在重复治疗24小时后注射[1-^13C]葡萄糖。电惊厥（ECS）6天（每天一次）。重复ECS使谷氨酰胺和GABA的合成减少，但谷氨酸的合成没有改变。从这些发现得出结论，rECS减少了从神经胶质细胞运输到神经元的谷氨酰胺合成的谷氨酸的GABA合成。3)为了估计脑TCA循环率并找出TCA循环率和神经元功能的相关性，将非侵入性^ 13 C-MR光谱技术应用于麻醉正常和MPTP诱导的患有帕金森病的猴子。正常猴脑的TCA循环率为0.56±0.058μmole/g/min，而MPTP治疗猴的该值下降了约30%。本研究认为，脑TCA循环率可能反映了神经元的活动。从这三个实验来看，脑氨基酸代谢与脑功能密切相关，这一点是毫无疑问的。谷氨酸合成率表明神经元活动，谷氨酰胺合成率也显示神经胶质代谢。最后我们相信，非侵入性测量脑氨基酸可以诊断脑部疾病。