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Identification of novel candidate genes for schizophrenia: using postmortem brain study

Research Project

Project/Area Number 12670937
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionKobe University Hospital

Principal Investigator

HASHIMOTO Takeshi  Kobe University Hospital, lecturer, 医学部附属病院, 講師 (60294229)

Co-Investigator(Kenkyū-buntansha) SHIRAKAWA Osamu  Kobe University Graduate School of Medicine, assistant professor, 大学院・医学系研究科, 助教授 (40243307)
MAEDA Kiyoshi  Kobe University Graduate School of Medicine, professor, 大学院・医学系研究科, 教授 (80116251)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsschizophrenia / postmortem brain / mRNA / gene / NMDA receptor / western blot / 前頭前野 / SAPAP / 精神分裂病 / 死後剖検脳 / 逆耐性 / グルタミン酸 / 候補遺伝子
Research Abstract

In our Scientific Research (C)(2) project from 2000 to 2002, we found changes in several signal transduction systems in the brains of animal models for schizophrenia, and the postmortem brains of schizophrenia. In addition, we analyzed gene expression in the postmortem brains of schizophrenia, in order to identify novel candidate genes for schizophrenia.
1) We found that calcineurin proteins decreased, while phosphothreonine-DARPP-32 increased in the striatum of Meth-sensitized rats. These results indicate that the activity of signal transduction via CaN is functionally decreased in the striatum of Meth-sensitized rats.
2) A deteriorated serotonin2A receptor-G protein q alpha (Gq alpha) -phosphoinositide-specific phospholipase C beta1 (PLC beta1) cascade has been found in the left, but not right, the superior temporal cortex of patients with schizophrenia.
3) We screened for genetic variations in the region of the NR2B subunit gene encoding the carboxyl-terminal intracellular domain in patients with schizophrenia and studied the association between schizophrenia and a novel polymorphism of the NR2B subunit gene. One silent mutation (2664C/T) was identified. No significant differences in the frequencies of 2664C/T genotypes and alleles were found between patients with schizophrenia and healthy comparison subjects.
4) We searched for genes that are induced by phencyclidine using the mRNA differential-display technique. Analyses of the nucleus accumbens of the treated animals and matched controls revealed changes in the expression of genes related to glutamatergic transmission and the intracellular transmission in the brain of the animal model for schizophrenia.
5) We investigated gene expression patterns in brain regions of patients with schizophrenia. A cDNA array was used to screen pools of samples from the prefrontal cortex of patients with schizophrenia. Of the examined genes, 33 mRNA were increased and 22 were decreased.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] 橋本 健志: "精神分裂病死後脳におけるポスホリパーゼCの変化"精神薬療研究年報. 32. 85-93 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 見野 耕一: "双極性障害に対する気分安定薬とリスペリドンの併用効果"臨床精神薬理. 4(8). 1153-1159 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 橋本健志: "救急医療における精神科的問題,精神運動興奮,臨床精神医学講座S7巻,総合診療における精神医学,三好好峰,前田潔編"中山書店. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishiguchi N., Shirakawa O., Ono H., Hashimoto T., Maeda K.: "Novel polymorphism in the gene region encoding the carboxyl-terminal intracellular domain of the human NMDA receptor 2B subunit: analysis of association with schizophrenia"Am J Psychiatry. 157. 1329-1331 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi M., Shirakawa O., Toyooka K., Kitamura N., Hashimoto T., Maeda K., Koizumi S., Wakabayashi K., Takahashi H., Someya H., Nawa H.: "Abnormal expression of brain-derived neurotrophic factor in the corticolimbic system of schizophrenic patients"Mol Psychiatry. 5 (3). 293-300 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Taniguchi T., Kawamata T., Mukai H., Hasegawa H., Isagawa T., Yasuda M., Hashimoto T., Terashima A., Nakai M., Ono Y., Tanaka C.: "Phosphorylation of tau is regulated by pkn"J Biol Chem. 276(13). 10025-10031 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakai K., Gao X-M., Hashimoto T., Tamminga CA.: "Traditional and new antipsychotic drugs differentially alter neurotransmission markers in basal ganglia-thalamocortical neural pathways"Synapse. 39 (2). 152-160 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shirakawa O., Kitamura N., Lin X-H., Hashimoto T., Maeda K.: "Abnormal neurochemical asymmetry in the temporal lobe of schizophrenia"Prog Neuropsychopharmacol Biol Psychiatry. 25 (4). 867-877 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Lin X-H., Hashimoto T., Kitamura N., Murakami N., Shirakawa O., Maeda K.: "Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine"Synapse. 44. 181-187 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono H., Shirakawa O., Kitamura N., Hashimoto T., Nishiguchi N., Nishimura A., Nushida H., Ueno Y., Maeda K.: "Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls"Mol Psychiatry. 7 (10). 1127-1132 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawamata T., Taniguchi T., Mikami H., Hashimoto T., Hasegawa H., San-Yu N., Terashima A., Nakai M., Yasuda M., Maeda K., Ono Y., Tanaka C., Tanaka C., McGeer PL., Ihara Y., eds.: "Possible role of tau phosphorylation on ER membrane in Alzheimer pathology, in Neuroscientific Basis of Dementia"Birkhauser.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono H, Shirakawa O, Kitamura N, Hashimoto T, Nishiguchi N, Nishimura A, Nushida H, Ueno Y, Maeda K: "Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls"Mol Psychiatry. 7(10). 1127-1132 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lin XH, Hashimoto T, Kitamura N, Murakami N, Shirakawa O, Maeda K: "Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine"Synapse. 44(3). 181-187 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aoyama S., Shirakawa O., Ono H,.Hashimoto T., Kajimoto Y., Maeda K.: "Mutation and association analysis of the DAP-1 gene with schizophrenia"Psychiatry and Clinical Neurosciences. 57(5)(In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shirakawa, O. et al.: "Abnormal neurochemical asymmetry in the temporal lobe of schizophrenia"Prog Neuropsychopharmacol Biol Psychiatry. 25(4). 867-877 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Lin, X-H, et al.: "Decreased Calcineurin and Increased Phosphothreonine-DARPP-32 in the Striatum of Rats Behaviourally Sensitized to Methamphetamine"SYNAPSE. (IN PRESS). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi,M: "Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients"Moles.Psychiatry. 5. 293-300 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishiquchi,N.: "a novel polymorphism in the region encoding the carboxyl-terminal intracellular domain of the human NMDA receptor 2B subunit and association analysis in schizophrenia"Am J Psychiatry. 157. 1329-1331 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] shirakawa,O: "Abnormal neurochemical asymmetry in the temporal lobe of schizophrenia"Prog-Neuro-Psychopharmacol.& Biol.Psychiatri.(In press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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