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

用核磁共振波谱对[1-^&lt；13&gt；C]葡萄糖和[2-^&lt；13&gt；C]葡萄糖中的谷氨酸、谷氨酰胺和GABA进行标记，研究脑内氨基酸代谢的变化1)为了检测[2-^&lt；13&gt；C]葡萄糖通过逆行途径进入脑内氨基酸的代谢去向，大鼠静脉注射葡萄糖。2)为了解大鼠脑内氨基酸代谢的变化，特别是神经元与神经细胞之间的代谢变化，根据脑功能的变化，在反复电休克(ECS)后24小时内注射[1-1]葡萄糖(13&GT；C)，连续6天(每天1次)。重复电刺激可降低谷氨酰胺和GABA的合成，但不影响谷氨酸的合成。这些结果表明，RECs减少了谷氨酰胺合成的谷氨酸合成的GABA，谷氨酰胺从胶质细胞运输到神经元。3)为了估计大脑TCA周期速率，寻找TCA周期速率与神经元功能的关系，应用无创性~(13)C-MR波谱技术对麻醉正常和MPTP诱导的帕金森病猴进行了研究。正常猴脑的三氯乙酸循环频率为0.56±0.058μ摩尔/克/分，MPTP处理猴脑的三氯乙酸循环频率降低约30%。本研究认为，大脑TCA循环率可以反映神经元的活动情况，从这三个实验来看，脑内氨基酸代谢与脑功能密切相关。谷氨酸合成率表示神经元的活性，谷氨酰胺合成率也表示神经胶质的代谢。最后，我们认为，脑内氨基酸的非侵入性测量使诊断脑部疾病成为可能。

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.