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2001 Fiscal Year Final Research Report Summary

A pharmacological approach to the molecular basis of disturbed brain information processing of schizophrenia

Research Project

Project/Area Number 12470192
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NISHIKAWA Toru  Tokyo Medical and Dental University Professor, 大学院・医歯学総合研究科, 教授 (00198441)

Co-Investigator(Kenkyū-buntansha) KURUMAJI Akeo  Tokyo Medical and Dental University Lecturer, 医学部・附属病院, 講師 (00251504)
Project Period (FY) 2000 – 2001
KeywordsSchizophrenia / Methamphetamine / Phencyclidine / Neocortex / Positive symptoms / Negative symptoms / RNA arbitrarily primed PCR / Postnatal development
Research Abstract

Schizophrenic symptoms occur after adolescence and the ability of psychotogenic drugs to induce schizophrenia-like psychosis is also age-dependent. Moreover, the behavioral responses to psychotogenic drugs in experimental animals apparently depend upon postnatal development. To obtain insight into the molecular basis of schizophrenia from a developmental point of view, we investigated in the developing rats the effects of schizophrenomimetic drugs, methamphetamine (MAP : a DA agonist which causes positive symptoms) and phencyclidine (PCP : a NMDA antagonist which causes positive and negative symptoms), on gene expression in the brain using a differential cloning technique and RT-PCR. We identified a developmentally-regulated and MAP-responsive (mrtl) or PCP-responsive (prtl) gene in the neocortex A selective D1 antagonist SCH23390 attenuated a MAP-induced upregulation of neocortical mrtlexpression, while a D2-preferring antagonist haloperidol failed to inhibit the increasing effects of PCP on prtl expression. Anti-mrt1 oligonucleotide blocked the ability of repeated MAP injection to produce reverse tolerance (behavioral sensitization : a model of the onset or relapse of positive symptoms of schizophrenia). The present data suggest that mrtl or prtl might be involved in the pathophysiology of positive or negative symptoms of schizophrenia, respectively.

  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Yamamoto N, Tomita U, Umino A, Nishikawa T: "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
  • [Publications] Murata M, Kashiwa A, Oshima A, Umino A, Kurachi M, Nishikawa T: "Nomifensine-induced c-fos mRNA expression in the discrete brain areas of the developing rat"Neurosci Lett. 303. 99-102 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] 黒田安計, 西川 徹: "覚せい剤による遺伝子発現"分子精神医学. 2. 31-37 (2002)

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      「研究成果報告書概要(和文)」より
  • [Publications] 車地暁生, 西川 徹: "精神分裂病の神経発達障害仮説から見た新薬開発の可能性"臨床精神薬理学. 4. 189-196 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] 山本直樹, 西川 徹: "新たな抗精神病薬開発の未来.特集「抗精神病薬50年のあゆみ」"Sschizophrenia Frontier. 2. 99-106 (2001)

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  • [Publications] 西川 徹: "D体のアミノ酸が脳ではたらく"科学. 71. 984-988 (2001)

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  • [Publications] 西川 徹: "覚醒剤精神病の分子生物学"Current Insights in Neurological Science. 9. 2-4 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] 柏 淳, 西川 徹: "メタアンフェタミン, コカイン 特集1「薬物依存の分子機構」"脳21. 4. 30-34 (2001)

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  • [Publications] Kurumaji A, Nomoto H, Yamada K, Yoshikawa T, Toru M: "No association of two missense variations of the benzodiazepine recepor (peripheral) gene and mood disorders in a Japanese sample"Am J Med Genet. 105. 172-175 (2001)

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  • [Publications] Ohtsuki T, Sakurai K, Dou H, Toru M, Yamakawa-Kobayashi K, Arinami T: "Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia"Mol Psychiacry. 6. 211-216 (2001)

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  • [Publications] Ishiguro H, Ohtsuki T, Okubo Y, Kurumaji A, Arinami T: "Association analysis of the pituitary adenyl cyclase activating peptide gene (PACAP) on chromosome 18p11 with schizophrenia and bipolar disorders"J Neural Transm. 108. 849-854 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kurumaji A, Kuroda T, Yamada K, Yoshikawa T, Toni M: "An association of the polymorphic repeat of tetranucleotide (TCAT) in the first intron of the human tyrosine hydroxylase gene with schizophrenia in a Japanese sample"J Neural Transm. 108. 489-495 (2001)

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  • [Publications] Kurumaji A, Nomoto H, Okano T, Toru M: "An association study between polymorphism of LlCAM gene and schizophrenia in a Japanese sample"Am J Med Genet. 105. 99-104 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Yoshikawa T, Kikuchi M, Saito K, Watanabe A, Yamada K, Shibuya H, Nankai M, Kurumaji A, Hattori E, Ishiguro H, Shimizu H, Okubo Y, Toru M, Detera-Wadleigh SD: "Evidence for association of the myo-inositol monophosphatase 2 (IMPA2) gene with schizophrenia in Japanese samples"Mol Psychiacry. 6. 202-210 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] 車地暁生, 西川 徹: "ストレス応答関連遺伝子と神経回路-ストレスによるc-fosとCRH遺伝子発現の変化"Current Insights in Neurological Science. 9(3). 2-4 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Tsuchida H, Yamamoto N, Kajii Y, Umino A, Nishikawa T: "Cloning of a D-serine-regulaed transcript dsr-1 from the rat cerebral cortex"Biochem Biophysiol Res Corn. 280. 1189-1196 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Shirayama Y, Mitsushio H, Takahashi K, Nishikawa T: "Differential effects of haloperidol on phencyclidine-induced reduction in substance P contents in rat brain regions"Synapse. 35. 292-299 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toda S, Kajii Y, Sato M, Nishikawa T: "Reciprocal expression of infant-and adult-preferring transcripts of CDCrel-lseptin gene in the rat neocortex"Biochem Biophysiol Res Corn. 273. 723-726 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 西川 徹: "精神疾患の克服 脳を守る 21世紀生命科学の展望"生体の科学. 51. 68-73 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 西川 徹: "不安の薬物療法-不安の神経生物学と新しい抗不安薬"医学のあゆみ. 192. 1133-1137 (2000)

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  • [Publications] 西川 徹, 山本直樹, 土田英人, 海野麻未, 川口直恵: "哺乳類脳における内在性D-セリン"日本神経精神薬理学雑誌. 20. 33-39 (2000)

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  • [Publications] 村岡新一郎, 西川 徹: "薬理学的精神分裂病モデル動物の分子病態 特集「精神分裂病へのアプローチ〜次世代への展望〜」"分子精神医学. 1. 19-26 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 西川 徹: "精神分裂病の分子メカニズムを探る"脳21. 3. 171-176 (2000)

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      「研究成果報告書概要(和文)」より
  • [Publications] 柏 淳, 西川 徹: "グルタミン酸と精神疾患"Brain Medical. 12. 181-186 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] 黒田安計, 西川 徹: "DNAチップ"臨床精神医学. 29. 1310-1312 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kajii Y, Toda S, Umino A, Nishikawa T: "A molecular approach to identify essential factors for establishment of psychostimulantinduced behavioral sensitization. In Contemporary Neuropsychiatry (Proceedings of the 3rd International Congress of Neuropsychiatry)"Springer-Verlag. 341-346 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 村岡新一郎, 西川 徹: "VII.モデル動物のゲノム解析によるアプローチ.臨床精神医学講座S11巻 精神疾患と遺伝"中山書店. 77-89 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto N, Tomita U, Umino A and Nishikawa T: "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
  • [Publications] Murata M, Kashiwa A, Oshima A, Umino A, Kurachi M and Nishikawa T: "Nomifensine-induced c-fos mRNA expression in the discrete brain areas of the developing rat"Neurosci Lett. 303. 99-102 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuchida H, Yamamoto N, Kajii Y, Umino A and Nishikawa T: "Cloning of a D-serine-regulated transcript dsr-l 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
  • [Publications] Shirayama Y, Mitsushio H, Takahashi K and Nishikawa T___________-: "Differential effects of haloperidol on phencyclidine-induced reduction in substance P contents in rat brain regions"Synapse. 35. 292-299 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toda S, Kajii Y, Sato M, and Nishikawa T: "Reciprocal expression of infant- and adult-preferring transcripts of CDCrel-1septin gene in the rat neocortex"Biochem Biophysiol Res Com. 273. 723-726 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kajii Y, Toda S, Umino A and Nishikawa T: "A molecular approach to identify essential factors for establishment of psychostimulant-induced behavioral sensitization"Contemporary Neuropsychiatry (Proceedings of the 3rd International Congress of Neuropsychiatry), pp. 341-346, Springer-Verlag, Tokyo. (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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