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STUDY ON THE D-SERINE METABORISM IN THE BRAIN AND APPLICATION FOR THE TREATMENT OF SCHIZOPHRENIA

Research Project

Project/Area Number 13671043
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionTokyo Medical and Dental University Graduate School (2002)
National Center of Neurology and Psychiatry (2001)

Principal Investigator

YAMAMOTO Naoki  Tokyo Medical and Dental University, Graduate School, Research Associate, 大学院・医歯学総合研究科, 助手 (70312296)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsD-serine / glutamate / NMDA receptor / schizophrenia / serine / 精神分裂病(分裂病) / 抗精神病薬 / コアゴニスト / 大脳皮質 / dsr-1
Research Abstract

D-Serine is an endogenous agonist of NMDA type glutamale receptor in the mammalian central nervous system. To obtain insight into the origin and metabolic pathway of D-serine at cellular and molecular levels, we have examined the effect of selective destruction of local neuronal cell bodies on the D-serine tissue content. The results suggested that the D-serine content was regulated by local neurons rather than axonal terminals projected from other areas. Interaction between neurons and glial cells might be crucial for the regulation of tissue and extracellular D-serine contents in the central nervous system. We have also isolated a D-serine-regulated transcript, dsr-2 from the rat cerebral neocortex. The dsr-1 was expressed predominantly in the brain, lung and testis. The expression of dsr-1 was significantly and selectively enhanced by D-serine in the cerebral neocortex. Further understanding of the molecular mechanism of endogenous D-serine metabolism in the brain will be important for the development of novel antipsychotic drugs.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Tsuchida H et al.: "Cloning of a D-serine-regulated transcript dsr-1 from the rat cerebral cortex"Biochem Biophysiol Res Com. 280. 1189-1196 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N et al.: "Uptake of D-serine by synaptosomal P2 fraction isolated from rat brain"Synapse. 42. 84-86 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N et al.: "Inhibition of thyroid hormone binding to the nuclear receptor by mobilization of free fatty acids"Horm Metab Res. 33. 131-137 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山本直樹, 西川徹: "新たな抗精神病薬開発の未来"Schizophrenia Frontier. 2. 99-106 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山本直樹 他: "内在性D-セリンの代謝機構の解明と難治性分裂病症状の治療への応用"精神薬療研究年報. 34. 185-191 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue et al.: "Identification of S1 proteins B2, C1 and D1 asAUF1 isoforms and their major role as hnRNP proteins"Biochem J. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山本直樹 他: "D-セリンの脳内代謝機構の解明と統合失調症新規薬物治療への応用"精神薬療研究年報. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 柏淳 他: "逆耐性現象に関与する新規遺伝子mrt1と相互作用する分子の検索"精神薬療研究年報. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山本直樹, 西川徹: "コカイン関連精神障害"日本臨床. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsuchida H et al.: "Cloning of a D-serine-regulated transcript dsr-1 from the rat cerebral cortex"Biochem Biophysiol Res Com. 280. 1189-1196 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N et al.: "Uptake of D-serine by synaptosomal P2 fraction isolated from rat brain"Synapse. 42. 84-86 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto n et al.: "Inhibition of thyroid hormone binding to the nuclear receptor by mobilization of free fatty acids"Horm Metab Res. 33. 131-137 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N, Nishikawa T: "Challenge and prospect of doveloping novel antipsychotic drugs"Schizophrenia Frontier. 2. 99-106 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N et al.: "Study on the molecular mechanism of D-serine and its application for the development of novel anti-schizophrenic drugs"Ann Rep Mitsubishi Pharma Res Found. 34. 185-192 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue A et al.: "Identification of SI proteins B2, C1 and D1 as AUF1 isoforms and their major role as hnRNP proteins"Biochem J. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N et al.: "Study on the mechanism of D-serine metabolism in the brain and clinical application for the treatment of schizophrenia"Ann Rep Mitsubishi Pharma Res Found. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kashiwa A et al.: "Characterization of the mrt1-interacting proteins"Ann Rep Mitsubishi Pharma Res Found. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N, Nishikawa T: "Cocaine-related disorders"Nihonrinsyo. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山本直樹, 西川徹: "コカイン関連精神障害"日本臨床. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山本直樹, 岩間久行, 海野麻未, 他: "D-セリンの脳内代謝機構の解明と統合失調症新規薬物治療への応用"精神薬療研究年報. 35(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamoto, N. et al.: "Characterization of D-serine-regulated genes in rat cerebral cortex"神経化学. 41;3. 329 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuchida, H. et al.: "Cloning of a D-serine-regulared transcript dsr-1 from the rat cerebral cortex"Biochem Biophys Res Commun. 280. 1189-1196 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, N. et al.: "Uptake of D-serine by synaptosomal P2 fraction isolated from rat brain"Synapse. 42. 84-86 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, N. et al.: "Uptake and release of D-serine in rat brain synaptosome"Amino Acids. 21. 55-56 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, N. et al.: "Inhibition of thyroid hormone binding to the nuclear receptor by mobilization of free fatty acids"Horm Metab Res. 33. 131-137 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山本直樹, 他: "新たな抗精神病薬開発の未来"Schizophrenia Frontier. 2. 99-106 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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