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Molecular biological study on the pathophysiology of bipolar disorders

Research Project

Project/Area Number 15591206
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KUSUMI Ichiro  Hokkaido Univ., Hokkaido Univ.Hospital, Lecturer, 病院, 講師 (30250426)

Co-Investigator(Kenkyū-buntansha) SUZUKI Katsuji  Hokkaido Univ., Hokkaido Univ.Hospital, Instructor, 病院・助手 (70344512)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsBipolar disorder / Ca-ATPase pump (SERCA) / Proteinkinase C / Calmojurin / Thapsigargin / ATP2A2 gene / XBP1 gene / Ca mobilization / カルシウム / 血小板 / 小胞体ストレス反応 / セロトニン / TCI / NEO-FFI / ATP2A2遺伝子変異 / 一過性細胞質内カルシウム増加 / 容量依存性カルシウム流入
Research Abstract

We examined thapsigargin (microsomal Ca-ATPase inhibitor)-induced transient intraplatelet calcium increase (TCI) and capcitative calcium entry (CCE) in the patients with bipolar disorder and major depressive disorder, and normal controls. There was no significant difference in thapsigargin-induced TCI or CCE among the three groups. However, in bipolar disorders, the inhibitory effect of proteinkinase C (PKC) stimulator on CCE was increased, and the stimulatory effect of PKC inhibitor on CCE was decreased. No significant differences in the effect of calmodulin inhibitor were observed among the three groups. These results suggest that the PKC function in bipolar disorders is compensatively enhanced to maintain the homeostasis of intracellular calcium (Ca) concentrations.
Enhanced Ca mobilization to various agonists in peripheral blood cells in one of a few confirmed biological markers for bipolar disorders. Recently, a polymorphism of XBP1, a pivotal gene in the endoplasmic reticulum stress response, was shown to contribute to the genetic risk factor for bipolar disorder. Thus, in this study, we examined the relationship between the XBP1 gene polymorphism and the Ca signaling in the platelets of healthy subjects. The present results suggest no significant difference in the basal Ca level or serotonin-induced Ca mobilization among normal subjects with -116C/C, C/G, G/G genotypes.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (4 results)

  • [Journal Article] Possible association between-116C/G polymorphism of the XBP1 gene and response to lithium in bipolar disorder2005

    • Author(s)
      Masui T
    • Journal Title

      Int J Nenropsychoparmacolagy (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Possible association between-116C/G polymorphism of the XBP1 gene and response to lithium in bipolar disorder2005

    • Author(s)
      Masui T
    • Journal Title

      Int J Neuropsychoparmacology (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Effects of lithium and valproate on agonist-induced platelet intracellular calcium mobilization : relevance to myosin light chain kinase2004

    • Author(s)
      Suzuki K
    • Journal Title

      Prog Neuro-Psychopharmacol & Biol Psychiatry 28

      Pages: 67-72

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lack of association between XBP1 genotype and calcium signaling in the platelets of healthy subjects2004

    • Author(s)
      Kusumi I
    • Journal Title

      Neuroscience Letters 369

      Pages: 1-3

    • NAID

      120000959306

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Effects of lithium and valproate on agonist-induced platelet intracellular calcium mobilization : relevance to myosin light chain.2004

    • Author(s)
      Suzuki K et al.
    • Journal Title

      Prog Neuro-psychopharmacol & Biol Psychiatry 28

      Pages: 67-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lack of association between XBP1 genotype and calcium Signaling in the platelets of healthy subjects.2004

    • Author(s)
      Kusumi I et al.
    • Journal Title

      Neuroscience Letters 369

      Pages: 1-3

    • NAID

      120000959306

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Darier病遺伝子と気分障害の病態研究2003

    • Author(s)
      久住 一郎
    • Journal Title

      分子精神医学 3

      Pages: 94-98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Altered 5-HT-induced calcium response in the presence of staurosporine in blood platelets from bipolar disorder patients2003

    • Author(s)
      Suzuki K
    • Journal Title

      Neuropsychoparmacology 28

      Pages: 1210-1214

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder2003

    • Author(s)
      Kakiuchi C
    • Journal Title

      Nature Genetics 35

      Pages: 171-175

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Altered 5-HT-induced calcium response in the presence of staurosporine in blood platelets from bipolar disorder patients.2003

    • Author(s)
      Suzuki K et al.
    • Journal Title

      Neuropsychopharmacology 28

      Pages: 1210-1214

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder.2003

    • Author(s)
      Kakiuchi C et al.
    • Journal Title

      Nature Genetics 35

      Pages: 171-175

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Possible association between-116C/G polymorphism of the XBP1 gene and response to lithium in bipolar disorder.

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

      Int J Neuropsychopharmacology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 久住 一郎: "Darier病遺伝子と気分障害の病態研究"分子精神医学. 3. 94-98 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki K: "Altered 5-HT-induced calcium response in the presence of staurosporine in blood platelets from bipolar disorder patients"Neuropsychoparmacology. 28. 1210-1214 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kakiuchi C: "Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder"Nature Genetics. 35. 171-175 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki K: "Effects of lithium and valproate on agonist-induced platelet intracellular calcium mobilization : relevance to myosin light chain kinase"Prog Neuro-Psychopharmacol & Biol Psychiatry. 28. 67-72 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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