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Activity-dependent gene expression of neuropeptide in neurons and screening of compounds effective for the expression

Research Project

Project/Area Number 15390022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

TSUDA Masaaki  Toyama med.& Pharm.Univ., Fac.Pharm.Sci., Professor, 薬学部, 教授 (80132736)

Co-Investigator(Kenkyū-buntansha) TABUCHI Akiko  Toyama Med.& Pharm.Univ., Fac.Pharm.Sci., Assistant Prof., 薬学部, 講師 (40303234)
IMAMURA Lisa  Toyama Med.& Pharm.Univ., Fac.Pharm.Sci., Head Researcher, 薬学部, 助手 (10232620)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥6,300,000 (Direct Cost: ¥6,300,000)
KeywordsBDNF / PACAP / calcium / CREB / NRSF / neurogenesis / cAMP / TrkB / 脳由来神経栄養因子BDNF / USF / サイレンサー / ERK / ハンチントン病
Research Abstract

Brain -derived nauotrophic factor (BDNF), a member of the neuzotrophin family, plays an important role in promoting neuronal survival, differentiation and synaptic plasticity. The BDNF gene consists of four short 5'-exons (exons I, II, III and IV) and a common 3'-exon V encoding a prepro-BDNF and four promoters, BDNF promoter I, II, III and IV (BDNF-PI, -PII, -PIII and -PIV) are located upstream of the 5'-exons, respectively. In this study, we demonstrated that the expression of BDNF exon III transcripts was secondarily induced by an administration of BDNF to the rat cortical neuronal cells in culture. This secondary induction was caused 24 hrs after the primary induction. And required the activation of TrkB receptors and the Ca^<2+> signalings for it. The regulational systems for this secondary induction is thought to be involeved in a consolidation of memory in the brain. On the other hand, the maximum expression of PACAP (pituitary adenylate cyclase-activating polypeptide) mRNA and its maximum promoter activity was obtained by a simultaneous addition of Ca^<2+> and cAMP signals in neurons. These signals can be evoked via activation of NMDA and dopamine D1 receptors, respetively., which is involeved in reward learning and drug addiction. In addition, we found that the PACAP mRNA stability was prolonged by the Ca^<2+> signals, which may be involved in synaptic plasticity. Finally, we found that neuro-restrictive silencing factor (NRSF) was repressive to the BDNF-PI and that the activation of BDNF-PI was induced irrespective of the repression of BDNF-PI by NRSF. This mechanisms regulating the BDNF exon I mRNA expression seems to be involved in the differentiation of neuronal stem cells in the dentate gyrus of hippocampus. We have already established the multi-screening method for surveying the drugs that are effective to enhance the BDNF gene transcription.

Report

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

    (22 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Publications (6 results)

  • [Journal Article] Additional repression of activity-dependent c-fos and BDNF mRNA expression by lipophilic compounds accompanying a decrease in Ca2+ influx into neurons2005

    • Author(s)
      Lisa Imamura
    • Journal Title

      NeuroToxicology 26

      Pages: 17-25

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Additional repression of activity-dependent c-fos and BDNF mRNA expression by lipophilic compounds accompanying a decrease in Ca2+ influx into neurons.2005

    • Author(s)
      Imamura L., Kurashina K., Kawahira T., Omoteno M., Tsuda M.
    • Journal Title

      Neuro Toxicology 26

      Pages: 17-25

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Additional repression of activity-dependent c-fos and BDNF mRNA expression by lipophilic compounds accompanying a decrease in Ca2+ influx into neurons2005

    • Author(s)
      Lisa Imamura
    • Journal Title

      Neuro Toxicology 25

      Pages: 17-25

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activity-dependent transcriptional activation and mRNA stabilization for cumulative expression of pituitary adenylate cyclase-activating polypeptide mRNA2004

    • Author(s)
      Mamoru Fukuchi
    • Journal Title

      J.Biol.Chem. 279

      Pages: 47856-47865

    • 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] Activity-dependent increase in b-amyloid precursor protein mRNA expression in neurons2004

    • Author(s)
      Akiko Tabuchi
    • Journal Title

      NeuroReport 15

      Pages: 1329-1333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calcium signal-mediated expression of the vasoactive intestinal polypeptide gene and its small contribution to the activity-dependent survival2004

    • Author(s)
      Mamoru Fukuchi
    • Journal Title

      J.Neurosci.Res. 77

      Pages: 26-34

    • 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] 細胞内カルシウムによる神経栄養因子の発現調節機構2004

    • Author(s)
      津田 正明
    • Journal Title

      Clinical Neuroscience, 神経栄養因子-その新しい展開 39

      Pages: 945-949

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 記憶・学習における神経活動依存性遺伝子発現と殺虫剤によるかく乱2004

    • Author(s)
      今村 理佐
    • Journal Title

      Brain medical 特集「脳の発達障害」 16

      Pages: 63-68

    • 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] Activity-dependent transcriptional activation and mRNA stabilization for cumulative expression of pituitary adenylate cyclase-activating polypeptide mRNA controlled By calcium and cAMP signals in neurons.2004

    • Author(s)
      Fukuchi M., Tabuchi A., Tsuda M.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 47856-47865

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activity-dependent increase in b-amyloid precursor protein mRNA expression in neurons.2004

    • Author(s)
      Tabuchi A., Fukuchi M., Kobayashi S., Suzuki T., Tsuda M.
    • Journal Title

      Neuro Report 15

      Pages: 1392-1333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Calcium signal-mediated expression of the vasoactive intestinal polypeptide gene and its small contribution to the activity-dependent survival of mouse cerebellar granule cells.2004

    • Author(s)
      Fukuchi M., Sakuragawa S., Tabuchi A., Tsuda M.
    • Journal Title

      J.Neurosci.Res. 77

      Pages: 26-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activity-dependent increase in b-amyloid precursor protein mRNA expression in neurons2004

    • Author(s)
      Akiko Tabuchi
    • Journal Title

      Neuro Report 15

      Pages: 1329-1333

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 細胞内カルシウムによる神経栄養因子の発現調節機構2004

    • Author(s)
      津田 正明
    • Journal Title

      Clinical Neuroscience,神経栄養因子-その新しい展開 39

      Pages: 945-949

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Alminum maltolate inhibits brain-derived neurotrophic factor-induced Free calcium elevations in cultured rat hippocampal neurons.2003

    • Author(s)
      Konoha K., Imamura L., Tsuda M., Kawahara M.
    • Journal Title

      Biomed.Res.Elements 14

      Pages: 290-292

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain-derived neurotrophic factor protects cultured rat hippocampal neurons From almium.2003

    • Author(s)
      Kawahara M., Kato-Negishi M., Hosoda R., Imamura L., Tsuda M., Kuroda Y.
    • Journal Title

      J.Inorg.Biochem. 97

      Pages: 124-131

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inactivation of aconitase during the apoptosis of mouse cerebellar granule neurons induced by a deprivation of membrane depolarisation.2003

    • Author(s)
      Tabuchi A., Funaji K., Nakatsubo J., Fukuchi M., Tsuchiya T., Tsuda M.
    • Journal Title

      J.Neurosci.Res. 71

      Pages: 504-515

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Mamoru Fukuchi: "Calcium signal-mediated expression of the vasoactive intestinal polypeptide gene and its small contribution to the activity-dependent survival of mouse cerebellar granule cells"J.Neurosci.Res.. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Masahiro Kawahara: "Brain-derived neurotrophic factor protects cultured rat hippocampal neurons from alminum maltolate neurotoxicity"J.Inorg.Biochem.. 97. 124-131 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akiko Tabuchi: "Inactivation of aconitase during the apoptosis of mouse cerebellar granule neurons induced by a deprivation of membrane depolarization"J.Neurosci.Res.. 71. 504-515 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Keiko Konoha: "Almiunum maltolate inhibits brain-derived neurotrophic factor-induced intracellular free calcium elevations in cultured rat hippocampal neurons"Biomed.Res.Elements. 14. 290-292 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 津田 正明: "細胞内カルシウムによる神経栄養因子の発現調節機構"Clinical Neuroscience「神経栄養因子-その新しい展開」. 22. 257-259 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 津田 正明: "脳由来神経栄養因子BDNFと記憶・学習"ファルマシア. 39. 945-949 (2003)

    • Related Report
      2003 Annual Research Report

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

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