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

通过用13 C-NMR光谱标记来自[1- 13 C]或[2- 13 C]葡萄糖的谷氨酸、谷氨酰胺和GABA来研究脑氨基酸代谢<13><13><13>。1）为了检测通过<13>回补途径从[2- 13 C]葡萄糖进入脑氨基酸的13 C-标记的代谢命运<13>，向大鼠静脉内注射推注的[2- 13 <13>C]葡萄糖。2）为了解脑氨基酸代谢的变化，特别是神经元与神经元之间的代谢转运，根据脑功能的改变，在<13>大鼠重复电休克（ECS）6天（1次/d）后24小时注射[1-^ C]葡萄糖，观察脑氨基酸代谢的变化。反复ECS可使谷氨酸和GABA的合成减少，但对谷氨酸的合成无明显影响。结论：rECS抑制了谷氨酸合成GABA的合成，而谷氨酸从神经元转运到神经元。3）为了估计脑TCA循环速率并发现TCA循环速率与神经元功能的相关性，将非侵入性的13 <13>C-MR波谱技术应用于麻醉的正常和MPTP诱导的帕金森病猴。正常猴脑TCA循环速率为0.56 ± 0.058 μmole/g/min，MPTP治疗组猴脑TCA循环速率降低约30%。本研究认为脑TCA循环率可反映神经元的活动，从这三个实验中，脑氨基酸代谢与脑功能密切相关是无疑的。谷氨酸的合成速率反映了神经元的活性，谷氨酰胺的合成速率也反映了神经胶质的代谢。最后，我们认为，脑氨基酸的无创性测量使诊断脑疾病成为可能。

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.