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The involvement of the BDNF signal transduction to the pathogenesis of ssstress-related psychiatric disorders

Research Project

Project/Area Number 07671046
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MORINOBU Shigeru  Yamagata University School of Medicine, Assstant Professor, 医学部, 講師 (30191042)

Co-Investigator(Kenkyū-buntansha) 川勝 忍  山形大学, 医学部, 助手 (00211178)
十束 志朗 (十束 支朗)  山形大学, 医学部, 教授 (80009133)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsBDNF / trkB / MAP kinase / Stress / phosphodiesterase / antidepressant / forskolin / trk B / Articlepreiiant / phothodiestrerait / Gurikolin / Trk B / MAP / phosdhodiesterase / Ant deorpsiant / Trk-B / 抗うつ薬 / Phrsphodiesterasc / ストレス
Research Abstract

To elucidate the involvement of the dysfunction of the BDNF signal transduction to the pathogenesis of stress-related psychiatric illnesses including depression, at first, the influence of various chronic stress paradigms on the expression of BDNF and trkB mRNA, and the activity of mitogen activated protein (MAP) kinase was examined in rat frontal cortex and hippocampus. In second, the effect of co-administration of a phosphodiesterase IV (PDE4) inhibitor on the induction of the BDNF signal transduction by antidepressant treatments, and NKH477 (water-soluble forskolin derivative) administration on the BDNF signal transduction were determined. Various acute and chronic stress paradigms significantly decreased the expression of BDNF and trkB mRNA in rat brain. While both acute and chronic restraint stress significantly increased the activity of MAP kinase in rat brain mediately after stress, both stress paradigms did not change the activity of MAP kinase i or 3 h after stress. The co-administration of a PDE4 inhibitor with an antidepressant as well as NKH477 administration significantly induced the expression of BDNF and trkB mRNA, and the increase in MAP kinase activity in rat brain. This co-administration (7 days) and NKH477 administration (1 h) shortened the time required for the significant induction of BDNF and trkB mRNA by antidepressant treatments (21 days). The results of this study may indicate that the decrease in BDNF mRNA expression by stress dose not affect the postsynaptic BDNF signa transductiorn However, it is possible that the enhancement of MAP kinase activity by stress may mask the decrease in MAP kinase activity due to the reduction of BDNF and trkB expression. The present results indicating the activation of the BDNF signal transduction by this co-administration and NKH477, raise the possibility that the stimulation of the cAMP signal transduction may have potential as a novel pharmacotherapy for depression.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Nibuya M,Mornobu S etal: "Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments" J.Neuroscience. 15. 7539-7547 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morinobu S,etal: "Regulation ofc-Fos and NGF1-A by antidepressant treatments" Synapse. 7. 273-278 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morinobu S,etal: "Stimulation of adenylyl cyclase and induction of brain-derived neurotrophic factor and trkB mRNA by NKH477.anoveland potent froskolin derivative" J.Neurochemistry. 72 (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nibuya M,Morinobu S,Duman RS: "Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments." J.Neurosci. 15. 7239-7547 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morinobu S,Strausbaugh H,Terwilliger R,Duman RS.: "Regulation of c-Fos and NGF 1-A by antidepressant treatments." Synapse. 25. 313-320 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morionobu S,Fujimaki K,Okuyama N,Takahashi M,Duman RS: "Stimulation of adenylyl cyclase and induction of brain-derived neurotrophic factor and trkB mRNA by NKH477, a novel and potent froskolin derivative." J.Neurochem. 72 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morinobu S: "Regulation of cfor and NGF1-A by antidepressant treatments" Synapse. 25. 313-320 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 森信繁: "感情障害発病に関わるcAMP情報伝達機能変化と遺伝子発現変化" 精神社会学組織. 98・11. 937-942 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 森信繁: "社会表因子情報伝達機能" 脳と精神の医学. 7・3. 273-278 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morinobu S: "Regvltior of C-fos and NGFI-A by artidepressant treatrents" Synu PS'C. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 高橋道宏 他: "抗うつ薬の脳内Brain-Derived Neirotunphic Poctor mRNA発現への効果" 日本神経精神薬理学雑誌. 15. 604-604 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 森信繁: "情報伝達機能研究の最近の進歩-BDHF情報伝達機能-" 脳と精神の医学. 7. (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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