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

用^<13>C- nmr谱法标记[1-^<13>C]或[2-^<13>C]葡萄糖中的谷氨酸、谷氨酰胺和GABA，研究脑氨基酸代谢。1)为检测[2-^<13>C]葡萄糖经回凝途径进入脑氨基酸的^<13>C-标记物的代谢命运，大鼠静脉注射[2-^<13>C]葡萄糖。从本研究中，我们得出结论，倒转通路通过谷氨酰胺从胶质细胞转运到神经元，参与谷氨酸和GABA的合成。2)为了解脑氨基酸代谢，特别是神经元与神经胶质之间的代谢运输的变化，根据脑功能的改变，大鼠经反复电休克（ECS）治疗后24小时注射[1-^<13>C]葡萄糖，持续6天（每天1次）。反复ECS可降低谷氨酰胺和GABA的合成。然而，谷氨酸的合成并没有改变。由此可见，rECS减少了谷氨酰胺从神经胶质细胞转运到神经元的谷氨酸合成GABA的过程。3)应用非侵入性^<13>C-MR波谱技术对麻醉正常和MPTP诱导的帕金森病猴进行脑TCA循环率测定，并寻找TCA循环率与神经元功能的相关性。正常猴脑TCA循环速率为0.56±0.058 μmol /g/min， MPTP组降低约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是毫无疑问的。谷氨酸合成率反映了神经元的活动，谷氨酰胺合成率也反映了神经胶质的代谢。最后，我们认为无创测量脑胺酸使脑部疾病的诊断成为可能。

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.