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Studies on the dopaminergic and glutamatergic neurones in the brain involved in schizophrenic etiology

Research Project

Project/Area Number 03454287
Research Category

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

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TORU Michio  Professor Tokyo Medical and Dental University and chairman Department of Neuropsychiatry, 医学部, 教授 (20013972)

Co-Investigator(Kenkyū-buntansha) WATANABE Akiko  Technician ditto, 医学部, 技官 (40210992)
YAMADA Kazuo  Resident ditto, 医学部, 医員
ISHIMARU Masahiko  Lecturer ditto, 医学部, 助手 (50242219)
KURUMAJI Akeo  Lecturer ditto, 医学部, 助手
SHIBUYA Haruo  Associate Professor ditto, 医学部, 助教授 (10158959)
南海 昌博  東京医科歯科大学, 医学部, 助手 (20218069)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsSchizophrenia / Dopamine / Glutamic Acid / NMDA receptor / Glycine binding / Chronic schizophrenia / ド-パミン / ド-パミンD2受容体 / クリシン結合部位 / アスパラギン酸 / シグマ受容体
Research Abstract

In this research we found a significant increase in NMDA-associated glycine binding site in chronic schizophrenic brains. A significant increase was observed in the 6 cerebral cortices (supramarginal cortex, angular cortex, somesthetic cortex. visual areal, visual areas 2 and 3, and premotor area). As the other two glutamic acid receptors, such as kainic acid and NMDA, the increased values of binding negatively correlate with glutamic acid values. Thus, the increase in glutamic acid receptors may be postsynaptic compensation for glutamatergic hypofunction in the chronic schizophrenic brain. Hypoglutamatergic states in the chronic brain may be induced by hyperdopaminergic states which have existed for long time in the schizophrenic brain. It is demonstrated that dopamine or its agonists inhibit the release ofglutamic acid from the striatal slices. Recent study using microdialysis showed the same results.Our findings suggest that hyperdopaminergic states coexist with hypoglutamatergic states in the chronic schizophrenic brain. New drugs which activate glutamatergicfunction in the brain could be useful to the chronic states of schizophrenia.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report

Research Products

(63 results)

All Other

All Publications (63 results)

  • [Publications] 融 道男 ほか: "分裂病の神経化学的病因仮説" 臨床精神医学. 21. 179-185 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 阿部 哲夫 ほか: "精神分裂病の脳形態のMRI研究と生物学的仮説" 臨床精神医学. 21. 187-196 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 山田 和男 ほか: "精神病惹起物質(MAP,PCP)のコレシストキニンmRNAレベルに及ぼす作用" 精神薬療基金研究年報. 23. 193-199 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 白石 弘巳 ほか: "抗精神薬大量投与中の精神分裂病患者にみられた熱射病の一例" 精神医学. 34. 627-235 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shibuya,H.ほか: "Shigma receptors in schizophrenic cerebral cortices" Neurochemical Research. 17. 983-990 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 長瀬 泰子 ほか: "精神分裂病患者の脳波コヒーレンスについてー無投薬例についてーの検討" 臨床脳波. 34. 373-379 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toru,M ほか: "Excitatory amino acidergic neurones in chronic schizophrenic brain" Molecular Neuropharmacology. 2. 241-243 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kurumaji,A. ほか: "2-〔 ^3H〕Amino-3-hydroxy-5-methylisoxazole-4-propionicacid binding to human cerebral cortical menbranes;minimal changes in postmortem brains of chronic schizophrelcs." Journal of Neurochmistry. 59. 829-837 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 石丸 昌彦 ほか: "慢性分裂病死後脳の大脳皮質におけるストリキニン非感受性グリシン結分部位に関する研究" 脳と精神の医学. 3. 315-319 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 融 道男: "精神分裂病ードパミンとグルタミン酸ニューロンの異常ー" Clinical Neuroscience. 10. 1174-1176 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ishimaru,M.ほか: "NMDA-Associated glycine binding site increases in schizophrenic brains" Biological Psychiatry. 32. 379-380 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Watanabe,A.ほか: "Measurement of glutamate,aspartate and glycine and its potential precursors in human brain using high-perfor-mance liquid chromatography by pre-column derivatization with diethylamino-azobenzene sulphonyl chloride" Journal of Chromatography. 583. 241-245 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Motohashi,N.ほか: "Effect of sulpiride and oxypertine on the dopaminergic system in the rat striatum" Neuropsychobiology. 25. 29-33 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nagase,Y.ほか: "EEG coherence in unmadicated schzophrenic patients:topographical study of predominantly never medicated cases." Biological Psychiatry. 32. 1028-1034 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 融 道男: "「精神分裂病はどこまでわかったか」第五章神経伝達異常はどこまで解明されたかードーパミン・グルタミン酸仮説を中心にー" 町山幸輝、樋口輝彦編、星和書店, 99-121 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 融 道男: "「精神医学と生物学の語らいーその源流と現代の視点」2章 生物学的精神医学における分裂病研究のストラテジーー序論" 中沢恒幸、小島卓也、三国雅彦編、学会出版センター, 17-21 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 車地 暁生 ほか: "「精神医学と生物学の語らいーその源流と現代の視点」3章 精神分裂病と興奮生アミノ酸" 中沢恒幸、小島卓也、三国雅彦編、学会出版センター, 23-40 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 融 道男(編): "抗精神病薬の副作用" ライフサイエンス, 126 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toru,M.: "Progress in biological hypothesis on schizophrenia" Jap.J.neuropsychopharmacol.13. 61-66 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toru,M.: "Mesolimbocortical dopamine system." Brain Nerve. 43. 319-329 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toru,M.: "Dopamine-related side-effects of antipsychicotic drugs." Psychoneuropharmacology symposium. 17. 25-32 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoshikawa,T., et al.: "Blockade of behavioral sensitization to methamphetamine by lesion of hippocampo-accumbal pathway." Life Science. 48. 1325-1332 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kurumaji,A. et al.: "alpha-[^3H]-Amino-3-hydroxy-5-methyl-isoxazole-4- propionic acid binding to human cortical membranes; mininal changes in postmortem brains of chronic schizophrenics." Journal of Neurochemistry. 59. 829-837 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toru,M.: "Schizophrenia-abnormalities of dopaminergic and glutamatergic neurones" Clinical Neuroscience. 10. 1174-1176 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kurumaji,A. and Toru.: "Schizophrenia and excitatory amino acids." Talks between Psychiatry and Biology--the Source and Present Aspects(ed.by Nakazawa,T.et al.,) Gakkai Shuppan Center, Tokyo. 23-40 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ishimaru,M. et al.: "NMDA-associated glycine binding site increase in, schizophrenic brains." Biological Psychiatry. 32. 379-380 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Motohashi,N. et al.: "Effect of sulpiride and oxypertine on the dopaminergic system in the rat striatum." Neuropsychobiology. 25. 29-33 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toru,M. et al.: "Neurochemical hypothesis of schizophrenic etiology." Jap.J.Clinical Psychiatry. 21. 179-185 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamada,K. et al.: "Effects of Psychogenic agents on Choecystokinin gene expression." Ann.Pep.Pharmacopsychiat. Res. Found.23. 193-199 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shibuya,H. et al.: "Sigma receptors in schizophrenic cerebral cortices." Neurochemical Research. 17. 983-990 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Toru,M. et al.: "Excitatory amino acidergic neurones in chronic schizophrenic brain." Molecular Neuropharmacol.2. 241-243 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 融 道男 ほか: "分裂病の神経化学的病因仮説" 臨床精神医学. 21. 179-185 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 阿部 哲夫ほか: "精神分裂病の脳形態のMRI研究と生物学的仮説" 臨床精神医学. 21. 187-196 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 山田 和男ほか: "精神病惹起物質(MAP,PCP)のコレシストキニンmRNAレベルに及ぼす作用" 精神薬療基金研究年報. 23. 193-199 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 白石 弘巳ほか: "抗精神薬大量投与中の精神分裂病患者にみられた熱射病の一例" 精神医学. 34. 027-235 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shibuya,H.ほか: "Shigma receptors in schizophrenic cerebral cortices" Neurochemical Research. 17. 983-990 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 長瀬 泰子ほか: "精神分裂病患者の脳波コヒーレンスについて -無投薬例について-の検討" 臨床脳波. 34. 373-379 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Toru,M ほか: "Excitatory amino acidergic neurones in chronic schizophrenic brain" Molecular Neuropharmacoloqy. 2. 241-243 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kurumaji,A. ほか: "2-[^3H]Amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to human cerebral cortical menbranes;minimal changes in postmortem brains of chronic schizophrenics." Journal of Neurochmistry. 59. 829-837 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 石丸 昌彦ほか: "慢性分裂病死後脳の大脳皮質におけるストリキニン非感受性グリシン結合部位に関する研究" 脳と精神の医学. 3. 315-319 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 融 道男: "精神分裂病ードパミンとグルタミン酸ニューロンの異常ー" Clinical Neuroscience. 10. 1174-1176 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ishimaru,M. ほか: "NMDA-Associated qlycine binding site increases in schizophrenic brains" Biological Psychiatry. 32. 379-380 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Watanabe,A. ほか: "Measurement of qlutamate,aspartate and qlycine and its potential precursors in human brain using high-perfor-mance liquid chromatography by pre-column derivatization with diethylamino-azobenzene sulphonyl chloride" journal of.Chromatography. 583. 241-245 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Motohashi,N. ほか: "Effect of sulpiride and oxypertine on the dopaminergic system in the rat striatum" Neuropsychobiology. 25. 29-33 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nagase,Y. ほか: "EEG coherence in unmadicated schzophrenic patients:topographical study of predominantly never medicated cases." Biological psychiatry. 32. 1028-1034 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 融 道男: "「精神分裂病はどこまでわかったか」 第5章神経伝達異常はどこまで解明されたか -ドーパミン・グルタミン酸仮説を中心に-" 町山幸輝、樋口輝彦編、星和書店, 99-121 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 融 道男: "「精神医学と生物学の語らい-その源流と現代の視点」 2章 生物学的精神医学における分裂病研究のストラテジー-序論" 中沢恒幸、小島卓也、三国雅彦編、学会出版センター, 11-21 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 車地 暁生ほか: "「精神医学と生物学の語らい-その源流と現代の視点」 3章 精神分裂病と興奮生アミノ酸" 中沢恒幸、小島卓也、三国雅彦編、学会出版センター, 23-40 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 融 道男 (編): "抗精神病薬の副作用" ライフサイエンス, 126 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 融 道男: "精神分裂病の生物学的仮説の発展" 神経精神薬理. 13. 61-66 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Yoshikawa,H.Shibuya,S.Kaneno,M.Toru: "Blockade of behavioral sensitization to methamphetamine by lesion of hippocampoーaccumbal pathway" Life Science. 48. 1325-1332 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 吉川 武男ほか: "分裂病あるいは逆耐性現象におけるグルタミン酸ニュ-ロンの関与" 精神薬療基金研究年報. 22. 247-254 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 融 道男: "中脳ー辺縁・前頭皮質dopamine系" 脳と神経. 43. 319-329 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 融 道男,山田 佐登留: "躁うつ病仮説の現況" 精神科治療学. 6. 1023-1029 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 融 道男: "精神病裂病とグルタミン酸" 医学のあゆみ. 159. 169 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Toru,A.Kurumaji,S.Kumashiro,M.Ishimaru,I.Suga,T.Nishikawa: "Dopaminergic and glutamatergic abnormalities in postmortem schizophrenic brain" Biological Psychiatry (Proc.of 5th World Congress of Biological Psychiatry). 1. 501-503 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 仙波 純一,融 道男: "せん妄の生化学的病因をめぐって" 集中治療. 3. 1163-1167 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 融 道男: "抗精神病薬のド-パミン関連副作用について" 精神神経薬理シンポジウム. 17. 25-32 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Toru,A.Kurumaji,S.Kumashiro et al.: "Excitatory amino acidergic neurons in chronic schizophrenic brain" Mol.Neuropharmacology.

    • Related Report
      1991 Annual Research Report
  • [Publications] A.Kurumaji,M.Ishimaru,M.Toru: "( ^3H)AMPA binding to human cerebral cortical membranes:minimal changes in postーmortem brains of chronic schizophrenia" J.Neurochem.

    • Related Report
      1991 Annual Research Report
  • [Publications] H.Shibuya,H.Mori,M.Toru: "Sigma receptors in schizophrenic cerebral cortices" Neurochem.Res.

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Toru,H.Shibuya,H.Mitsushio,T.Nishikawa,I.Suga,Y.Kiuchi (ed.by T.Nakazawa): "Taniguchi Symposia on Brain Sciences No.14:Biological Basis of Schizophrenic Disorders" Karger,Basel, 91-100 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 融 道男(編): "精神科難治症例ー私の治療" 中外医学社, 369 (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-03-31   Modified: 2016-04-21  

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