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

Research Project

Project/Area Number 10680724
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionInstitute of Life Science, Soka University

Principal Investigator

KANAMATSU Tomoyuki  Institute of Life Science, Soka University, Associate Professor, 生命科学研究所, 助教授 (30104201)

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)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
KeywordsBrain / animal model of neurological disfunction / monkey / glutamate / glutamine / ^<13>C-glucose / magnetic resonance spectroscopy / non-invasive measurement of brain function / パーキンソン病 / ドーパミン / MPTP / [2-^<13>C]-ブドウ糖 / ビククリン / γ-アミノ酪酸(GABA) / てんかん発作 / ^<13>C / 反復電気痙攣刺激 / ガンマ-アミノ酪酸(GABA)
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.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] H.Watnabe, Y.Ishihara, K.Okamoto, K.Oshio, T.Kanamatsu, Y.Tsukada: "In vivo 3D localized ^<13>C spectroscopy using modifed INEPT and DEPT."J.Mag.Res.. 134. 214-222 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Tsukada, T.Kanamatsu, H.Watanabe, K.Okamoto: "In vivo investigation of glutamate-glutamine metabolism in hyper-ammonemic monkey brain using ^<13>C magnetic resonance spectroscopy."Dev.Neurosci.. 20. 427-433 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Okamoto, M.Umeda, Y.Ishihara, H.Watanabe, M.Oda, T.Kanamatsu, Y.Tsukada: "Human brain metabolism measurements by [1-^<13>C] glucose administration using high SNR ^<13>C-MRS pluse sequence."^<13>C Igaku. 8. 38-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kanamatsu, H.Takahara, Y.Tsukada: "Glutamine synthesized in astroglia is regarded as a precursor of GABA."^<13>C Igaku. 8. 40-41 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Okamoto, M.Umeda, Y.Ishihara, H.Watanabe, M.Oda, T.Kanamatsu, Y.Tsukada: "Non-invasive measurment of metabolism by ^<13>C-MRS"Medical Review. 71. 37-42 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Tsukada, T.Kanamatsu, H.Takahara: "Neurotransmitter release from the medial hyperstratum ventral of the chick forebrain accompanying filial imprinting behavior measured by in vivo microdialysis."Neurochem.Res.. 24. 315-320 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kanamatsu, Y.Tsukada: "Effects of ammonia on the anaplerotic pathway and amino acid metabolism in the brain : an ex vivo ^<13>C-NMR spectroscopic study of rats after administering [2-^<13>C] glucose with or without ammonium acetate."Brain Res.. 841. 11-19 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kanamatsu, T.Yuasa: "Effect of electroconvulsive shock on rat brain metabolism : Study using ^<13>C-magnetic resonance spectroscopy (^<13>C-MRS)."Neurological Medicine. 51. 405-412 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Watanabe, M.Umeda, Y.Ishihara, K.Okamoto, M.Oda, T.Kanamatsu, Y.Tsukada: "High sensitive in vivo ^<13>C-metabolite imaging using multislice HSQC."^<13>C Igaku. 9. 8-9 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kanamatsu, H.Takahara, Y.Tsukada, T.Yuasa: "Effects of repeated electroconvulsive shock on glucose-amino acid metabolism in rat brain with [1-^<13>C] glucose administration."^<13>C Igaku. 9. 10-11 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Watanabe, Y.Ishihara, K.Okamoto, K.Oshio, T.Kanamatsu, Y.Tsukada: "3D localized ^1H-^<13>C heteronuclear single-quantum choherence correlation spectroscop in vivo."Mag.Reson.Med.. 43. 200-210 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Watanabe, M.Umeda, Y.Ishihara, K.Okamoto, T.Kanamatsu, Y.Tsukada: "Human brain glucose metabolism mapping using multisclice 2D ^1H-^<13>C correlation HSQC spectrosccopy."Mag.Reson.Med.. 43. 525-533 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Ishihara, H.Watanabe, K.Okamoto, T.Kanamatsu, Y.Tsukada: "Temperature monitoring of intemal body heating induced by docoupling pulses in aminal ^<13>C-MRS experiments."Magn.Reson.Med.. 43. 796-803 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Kanamatsu, A.B.Patel, J.Wall, D.L.Rothman, K.B.Behar, R.G.Shulman: "Changes of glucose-amino acid metabolism during bicuculline seizures."^<13>C Igaku. 10. 34-35 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Watanabe, M.Umeda, Y.Ishihara, K.Okamoto, M.Oda, T.Kanamtsu, Y.Tsukada: "High sensitive in vivo ^<13>C metabolite imaging using multislice HSQC."^<13>C Igaku. 10. 36-37 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Watanabe,Y.Ishihara.K.Okamoto,K.Oshio,T.Kanamatsu,Y.Tsukada: "3D localized ^1H-^<13>C heteronuclear single-quantum choherence correlation spectroscopy in vivo"Mag.Reson.Med.. 43. 200-210 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Watanabe,M.Umeda,Y.Ishihara,K.Okamoto,T.Kanamatsu,Y.Tsukada: "Human brain glucose metabolism mapping using multislice 2D ^1H-^<13>C correlation HSQC spectroscopy"Mag.Reson.Med.. 43. 525-533 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Ishihara,H.Watanabe,K.Okamoto,T.Kanamatsu,Y.Tsukada: "Temperature monitoring of internal body heating induced by decoupling pulses in animal ^<13>C-MRS experiments"Mag.Reson.Med.. 43. 796-803 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 金松知幸,A.B.Patel,J.Wall,D.L.Rothman,K.B.Behar,R.G.Shulman: "Bicucullineによって誘発されたてんかん発作中のブドウ糖-アミノ酸代謝の変化"^<13>C医学. 10. 34-35 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 渡邉英宏,梅田国朗,石原康利,岡本和也,小田正記,金松知幸,塚田裕三: "^<13>C代謝物イメージング法の高感度化 第二報"^<13>C医学. 10. 36-37 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 金松知幸等: "Bicucullineによって誘発されたてんかん発作中のブドウ糖-アミノ酸代謝の変化"^<13>C医学. Vol.10. 34-35 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 金松知幸、湯浅龍彦: "電気刺激による脳内代謝の変化-^<13>C-MRスペクトロスコピ-法(^<13>C-MRS)による研究"神経内科. Vol.51. 405-412 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] T.Kanamatsu Y.Tsukada: "Effects of ammonia on the anaplerotic pathway and amiono acid metabolism in the brain:an ex vivo ^<13>C NMR spectroscopic study of rats after administering [2-^<13>C] glucose with or without ammonium acetate"Brain Research. Vol.841. 11-19 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 金松知幸、高原ひろみ、塚田裕三、湯浅龍彦: "反復電気痙攣刺激に伴う脳内ブドウ糖、アミノ酸代謝の変化-^<13>C-ブドウ糖を用いて-" ^<13>C医学. Vol.9(In press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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