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Mitochondrial dysfunction of neuronal cells and impaired metabolism of amino acid neurotransmitters in hepatic encephalopathy

Research Project

Project/Area Number 02454231
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionToyama Medical and Pharmaceutical University

Principal Investigator

WATANABE Akiharu  Professor, Third Department of Internal Medicine, 医学部内科学第3, 教授 (00033390)

Co-Investigator(Kenkyū-buntansha) SAITOH Seiji  Assistant Professor, Third Department of Internal Medicine, 附属病院第3内科, 講師 (70126522)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsSynaptosomes / Neuronal cells / Hepatic encephalopathy / Glutaminase / Ammonia / Neurotransmitter amino acids / Brain stem / GABA / 急性肝不全 / 神細細胞
Research Abstract

The binding of inhibitory and excitatory neurotransmitter amino acids to the synaptosomal membranes from various brain regions such as brain stem was investigated using D-galactosamine-treated rats with fulminant hepatic failure. Furthermore, isolation and primary culture of glial and neuronal cells from normal and liver-injured rats were tried in the present study.
1. The binding study of GABA (inhibitory neurotransmitter) and glutamic acid (excitatory neurotransmitter) to the membrane fraction of neuronal cells uas analysed according to Schafer's method. Although glutamine centents in the synaptosomes of the brain stem increased in hepatic failure rats, the binding of glutamine to the synaptosomal membrane (Km, Vmax) did not change in these rats. There was no alteration of glutamine decarboxylase activity and the binding of GABA to neuronal membranes in hepatic failure rats.
2. Glutaminase activity from the synaptosomal mitochondria was significantly inhibited by ammonia, short chain fatty acids, glutamic acid or GABA, and the data indicate that this might be a kind of feed-back inhibition under the high ammonia state.
3. The isolation of rats glial and neuronal cells was carried out according to the method of Farooq ; the slices of the brain stem was treated by trypsin and separated by the discontinious centrifugation on Ficoll. The cells obtained were microscopically and biochemically similar to the previously reported data. However, primary culture can not be successful, aryd thus further study should be continued with improvement of the culture system. The functional interaction of glia cells and neuronal cells will be further studied.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 渡辺 明治: "肝性脳症の成因と治療における分枝鎖アミノ酸の意義" ウイルス肝炎研究財団研究業績集. 11-19 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 渡辺 明治: "肝性脳症の病態と治療ー潜在性脳症を中心として" 富山医科薬科大学医誌. 3. 29-31 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Satoru Tominaga Akiharu Watanabe Takao Tsuji: "Synergistic effect of bile acid,endotoxin,and ammonia on brain edema" Metabolic Brain Disease. 6. 93-105 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akiharu Watanabe Tetsuya Shiota Takao Tsuji: "Cerebral edema during hepatic encephalopathy in fulminant hepatic failure" Journal of Medicine. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akiharu Watanabe Tetsuya Shiota: "Effect of ammonia and other putative substances on glutaminase activity in synaptosomal mitochondria from rat cerebrum and brain stem" Res.Commun.Chem.Pathol.Pharmacol.(1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 渡辺 明治: "最新内科学大系49肝硬変" 中山書書(分担), 15 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Satoru Tominaga, Akiharu Watanabe, Takao Tsuji: "Synergistic effect of bile acid, endotoxin, and ammonia on brain edema." Betabol. Brain Dis.6. 93-105 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akiharu Watanabe, Tetsuya Shiota, Takao Tsuji: "Cerebral edema during hepatic encephalopathy in fulminant hepatic failure." J. Med.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akiharu Watanabe, Tetsuya Shiota: "Effect of ammonia and other putative substances on glutaminase activity in synaptosomal mitochondria from rat cerebrum and brain stem" Res. Commun. Chem. Pathol. Pharmacol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Akiharu Watanabe;Tetsuya Shiota;Takao Tsuji: "Cerebral edema during hepatic encephalopathy in fulminant hepatic failure" Journal of Medicine. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akiharu Watanabe;Tetsuya Shiota: "Effect of ammonia and other putative sulstances on glutaminase activity in synaptosomal mitochondria from rat cerebrum and brain stem" Res.Commun.Chem.Pathel.Pharmacol.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Satoru Tominaga;Akiharu Watanabe;Takao Tsuji: "Synergistic effect of bile acid,endotoxin,and ammonia on brain edema" Metabolic Brain Disease. 6. 93-105 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 渡辺 明治: "肝性脳癌の病態と治療ー潜在性脳症を中心として" 富山医科薬科大学医誌. 3. 29-31 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Watanabe,A.: "Inhibitory effect of ammonia and other neurotoxic substances on type I glutaminase activity in synaptosomal mitochondria from rat brain stem" Exp.Med.

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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