2000 Fiscal Year Final Research Report Summary
Studies of brain amino acid metabolism in an animal model of neurological disfunction with ^<13>C-NMR spectroscopy
| Project/Area Number |
10680724
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Institute of Life Science, Soka University |
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Principal Investigator |
KANAMATSU Tomoyuki Institute of Life Science, Soka University, Associate Professor, 生命科学研究所, 助教授 (30104201)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASE Sayaka Institute of Life Science, Soka University, Associate Professor, 生命科学研究所, 助教授 (60236221)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Brain / animal model of neurological disfunction / monkey / glutamate / glutamine / ^<13>C-glucose / magnetic resonance spectroscopy / non-invasive measurement of brain function |
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| Research Abstract |
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.
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