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AN INVESTIGATION OF BRAIN MOLECULAR MECHANISM RELATED TO ONSET AND PATHOPHYSIOLOGY OF ANXIETY DISORDERS

Research Project

Project/Area Number 17591196
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

Principal Investigator

KURUMAJI Akeo  Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院医歯学総合研究科, 准教授 (00251504)

Co-Investigator(Kenkyū-buntansha) KASHIWA Atsushi  Tokyo Medical and Dental University Medical Hospital, Psychiatry, Assistant Professor, 医学部附属病院, 講師 (10301227)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsANXIETY DISORDERS / HIPPOCAMPUS / ANXIOGENIC DRUG / GENE EXPRESSION / STRESS / AGING / RT-PCR / MICROARRAY / 大脳皮質 / 遺伝子 / FG7142 / in situ hybridization
Research Abstract

We examined an effect of FG 7142, and anxiogenic drug, on gene expression in the hippocampus, where play an important role in the pathophysiology of anxiety disorders, of three developmental stages of mice to find some age-dependent and stress-responsive genes. A microarray experiment revealed that FG 7142 produced a significant increase in the expression of 13 genes in the hippocampus of 18-month old mice. A quantitative RT-PCR method reproduced a statistically significant increase in the level of mRNA of 11 genes, but not of two genes. The drug-induced increase in the mRNA of 11 genes was also observed in the hippocampus of 8-week old mice, but not of 8-day old mice.
The RT-PCR experiment examined an effect of acute immobilization stress on the expression of 11 genes in the hippocampus of the old, the young adult and the neonatal mice. There was a statistically significant up-regulation in mRNA of three of 11 genes in the old mice, while only two of the three genes were enhanced by the stress in the young adult mice. However, none of 11 genes was changed by stress in the gene expression of the new born animals. The magnitude of increase induced by stress in the serum level of corticosterone was similar (from 50 to 120%) among the three stages of mice, while the basal level of the infant was about one tenth of that of older mice.
Consequently, the present study demonstrated that there were age-related and stress-responsive genes in the hippocampus of mice. Further studies are required to clarify the molecular cascade of the stress response.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (20 results)

All 2007 2006 2005

All Journal Article (16 results) Book (4 results)

  • [Journal Article] Selective serotonin reuptake inhibitors, fluoxetine and paroxetine, attenuate the expression of the established behavioral sensitization induced by methamphetamine2007

    • Author(s)
      Kaneko Y et al.
    • Journal Title

      Neuropsychopharmacol 32

      Pages: 658-664

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective serotonin reuptake inhibitors, fluoxetine and paroxetine, attenuate the expression of the established behavioral sensitization induced by methamphetamine.2007

    • Author(s)
      Kaneko Y et al.
    • Journal Title

      Neuropsychopharmacol 32

      Pages: 658-664

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective serotonin reuptake inhibitors, fluoxetine and paroxetine, attenuate the expression of the established behavioral sensitization induced by methamphetamine2007

    • Author(s)
      Kaneko Y, et al.
    • Journal Title

      Neuropsychopharmacol 32

      Pages: 658-664

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evidence for involvement of glial cell activity in the control of extracellular D-serine contents in the rat2006

    • Author(s)
      S.Kanematsu et al.
    • Journal Title

      J Neural Transm 113

      Pages: 1717-1721

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 修正型電気けいれん療法(m-ECT)が著効した両室性ペースメーカーを植え込まれたうつ病の1症例2006

    • Author(s)
      光定博生 他
    • Journal Title

      臨床精神医学 35

      Pages: 1207-1212

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 経過中にせん妄を呈した血管性うつ病の1症例2006

    • Author(s)
      横溝美緒 他
    • Journal Title

      精神科 8

      Pages: 165-170

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 新規抗精神病薬-急性に対する使い方-2006

    • Author(s)
      熱田英範, 車地暁生
    • Journal Title

      Current Therapy 24

      Pages: 60-64

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Evidence for involvement of glial cell activity in the control of extracellular D-serine contents in the rat brain.2006

    • Author(s)
      Kanematsu S et al.
    • Journal Title

      J Neural Transm 113

      Pages: 1717-1721

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neuroanatomical and molecular changes in stress responses. PTSD brain mechanisms and clinical implications.2006

    • Author(s)
      Nishikawa T et al.
    • Journal Title

      Springer-Verlag, Tokyo (Kato N, Kawata M, Pitman RK (eds.))

      Pages: 3-11

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Evidence for involvement of glial cell activity in the control of extracellular D-serine contents in the rat2006

    • Author(s)
      S.Kanematsu, et al.
    • Journal Title

      J Neural Transm 113

      Pages: 1717-1721

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 修正型電気けいれん療法(M-ECT)が著効した両室性ペースメーカーを植え込まれたうつ病の1症例2006

    • Author(s)
      光定博生, 他4名
    • Journal Title

      臨床精神医学 35

      Pages: 1207-1212

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 経過中にせん妄を呈した血管性うつ病の1症例2006

    • Author(s)
      横溝美緒, 他7名
    • Journal Title

      精神科 8

      Pages: 165-170

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 統合失調症の神経発達障害仮説と神経変性仮説2005

    • Author(s)
      車地 暁生
    • Journal Title

      精神科治療学 20

      Pages: 3-10

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 統合失調症の病理病態生理成因-神経化学2005

    • Author(s)
      車地 暁生
    • Journal Title

      最新医学別冊 新しい診断と治療のABC 32 32

      Pages: 39-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 治療経過中に退行し、復職プログラムと集団精神療法が有効であった遷延うつ病の症例2005

    • Author(s)
      黒田裕子 他
    • Journal Title

      精神科 6

      Pages: 65-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 統合失調症の病理病態生理成因-神経化学2005

    • Author(s)
      車地 暁生
    • Journal Title

      最新医学別冊 新しい診断と治療のABC32 32

      Pages: 39-47

    • Related Report
      2005 Annual Research Report
  • [Book] 身体表現性障害を経過中にBipolarII Disorderを呈し、炭酸リチウム投与によって寛解に至った1症例(Bipolar Disorder研究会編)(Bipolar Disorder 4)2006

    • Author(s)
      車地暁生 他
    • Publisher
      アルタ出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Neuroanatomical and molecular changes in stress responses. PTSD brain mechanisms and clinical implications (Kato N, Kawata M and Pitman RK (eds.))2006

    • Author(s)
      Nishikawa T et al.
    • Publisher
      Springer-Verlag
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Bipolar Disorder 4(Bipolar Disorder研究会編)(アルタ出版)2006

    • Author(s)
      車地暁生, 他7名
    • Publisher
      身体表現性障害を経過中にBipolarII Disorderを呈し、炭酸リチウム投与によって寛解に至った1症例.
    • Related Report
      2006 Annual Research Report
  • [Book] Neuroantomical and molecular changes in stress responses during early life: implication for stress disorders.In PTSD: Brain Mechanism and Clinical Imolications. Eds by N. Kato, M Kawata, R.K. Pitman2006

    • Author(s)
      T.Nishikawa, A., Kurumaji, T.Ito, A., Umino, S.Ishii
    • Publisher
      Springer
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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