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The alteration of adult neural network by pre/post-natal alcohol and addictive drug exposure

Research Project

Project/Area Number 16390327
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

SAITO Toshikazu  Sapporo Medical Univ, Dept of Neuropsy, Professor, 医学部, 教授 (50128518)

Co-Investigator(Kenkyū-buntansha) IKEDA Hiroshi  Sapporo Medical Univ, Dept of Neuropsy, Assistant Professor, 医学部, 講師 (30232193)
HASHIMOTO Eri  Sapporo Medical Univ, Dept of Neuropsy, Assistant Professor, 医学部, 講師 (30301401)
SOHMA Hitoshi  Sapporo Medical Univ, Dept of Bioengineering, Assistant Professor, 医学部, 助教授 (70226702)
YAMAMOTO Megumi  Sapporo Medical Univ, Dept of Neuropsy, Assistant Professor, 医学部, 講師 (90347170)
KATO Tadafumi  Riken Brain Institute, Aging and Psychiatric Research Group, Group Director, 老化・精神疾患研究グループ, グループディレクター (30214381)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2004: ¥8,600,000 (Direct Cost: ¥8,600,000)
Keywordsalcohol damage / neural stem cell / fetal alcohol syndrome / neurogenesis / regenerative medicine / BDNF / NRSF / REST / CREB / エタノール / 神経栄養因子 / MAP2 / リン酸化Akt / リン酸化Erk
Research Abstract

We analyzed cellbiological change of damaged brain by prenatal and young adult ethanol exposure, focusing on the alteration of neural network maintenance function. First, we investigated the effect of ethanol on the Ca^<2+> signaling and Ca^<2+> binding protein using cultured cells and animal models and demonstrated pivotal role of NF-kB activation and CREB reduction on the impairment of premature neuronal cell development and mature neuron survival. We next proceeded the analysis of molecular mechanism of brain neural network change by ethanol using cultured neural stem cells derived from fetal rat brain, and revealed that ethanol decreased neural stem cell differentiation to neurons, but promoted their differentiation to astrocytes and to oligodendrocytes dose dependently. These were indicated that the reduction of neurotrophic factor signaling and activation of transcriptional suppressor NRSF/REST play an important role on the neural stem function change induced by ethanol. In the additional experiment, we demonstrated the decrease activity of neural stem cell proliferation and increase of gliogenesis in cultured neural stem cells derived from the fetal alcohol syndrome model. It was also indicated that the differentiation of neural stem cells derived from the model, sensitively decreased by the 2nd time ethanol exposure. These results strongly suggest that prenatal exposure of ethanol can induce neural stem cell function impairment in fetus brain, and might cause serious incidence on the neural network abnormal development of children's brain.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (19 results)

All 2006 2005 2004

All Journal Article (18 results) Book (1 results)

  • [Journal Article] Implication of increased NRSF/REST binding activity in the mechanism of ethanol inhibition of neuronal differentiation.2006

    • Author(s)
      Tateno M et al.
    • Journal Title

      J Neural Transm 113(3)

      Pages: 283-293

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Implication of increased NRSF/REST binding activity in the mechanism of ethanol inhibition of neuronal differentiation.2006

    • Author(s)
      Tateno M
    • Journal Title

      J Neural Transm 113(3)

      Pages: 283-293

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation of brain derived neurotrophic factor (BDNF) by ethanol and cytoprotective effect of exogenous BDNF against ethanol damage in neuronal cells2005

    • Author(s)
      Sakai R et al.
    • Journal Title

      J Neural Transm 112(8)

      Pages: 1005-1013

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] The effect of ethanol on cell fate determination of neural stem cells2005

    • Author(s)
      Tateno M et al.
    • Journal Title

      Alcohol Clin Exp Res 29(12S)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Neurotrophic factor signaling in alcoholism2005

    • Author(s)
      Pandy et al.
    • Journal Title

      Alcohol Clin Exp Res 29(6)

      Pages: 1098-1105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] The effects of ethanol on neuronal and glial differentiation and devepopment2005

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

      Alcohol Clin Exp Res 29(11)

      Pages: 2070-2075

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] アルコールによる神経新生抑制における転写因子NRSF/RESTの役割2005

    • Author(s)
      館農 勝 他
    • Journal Title

      アルコールと医学生物学 25

      Pages: 43-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Attenuation of brain derived neurotrophic factor (BDNF) by ethanol and cytoprotective effect of exogenous BDNF against ethanol damage in neuronal cells.2005

    • Author(s)
      Sakai R
    • Journal Title

      J Neural Transm 112(8)

      Pages: 1005-1013

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The effect of ethanol on cell fate determination of neural stem cells.2005

    • Author(s)
      Tateno M
    • Journal Title

      Alcohol Clin Exp Res 29(12S)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Neurotrophic factor signaling in alcoholism2005

    • Author(s)
      Pandy
    • Journal Title

      Alcohol Clin Exp Res 29(6)

      Pages: 1098-1105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The effects of ethanol on neuronal and glial differentiation and development.2005

    • Author(s)
      Saito T
    • Journal Title

      Alcohol Clin Exp Res 29(11)

      Pages: 2070-2075

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] アルコール依存の分子生物学2005

    • Author(s)
      鵜飼 渉 他
    • Journal Title

      Curr Insights Neurol Sci 13(3)

      Pages: 2-4

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Attenuation of brain-derived neurotrophic factor(BDNF) by thanol and cytoprotective effect on exogenous BDNF against ethanol damage in neuronal cells2004

    • Author(s)
      Sakai R, Hashimoto E, et al.
    • Journal Title

      J Neural Transm (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ethanol inhibition of neural stem cell differentiation is reduced by neurotrophic factors.2004

    • Author(s)
      Tateno M, Hashimoto E, et al.
    • Journal Title

      Alcohol Clin Exp Res 8Suppl

    • Related Report
      2004 Annual Research Report
  • [Journal Article] エタノールによる脳内神経回路網改変の可能性 エタノールの神経細胞の新生及び生存に与える影響2004

    • Author(s)
      山本 恵 他
    • Journal Title

      日本アルコール・薬物医学会雑誌 39・1

      Pages: 51-60

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 薬物・アルコールの生物学的研究 エタノールによる神経幹細胞内シグナル伝達変化と分化制御2004

    • Author(s)
      齋藤 利和 他
    • Journal Title

      日本アルコール・薬物医学会雑誌 39・4

      Pages: 276-277

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 依存症のニューロサイエンス アルコール依存症の神経生物学2004

    • Author(s)
      山本 恵 他
    • Journal Title

      Clinical Neuroscience 22・6

      Pages: 670-672

    • Related Report
      2004 Annual Research Report
  • [Journal Article] エタノールによる神経幹細胞内シグナル変化と分化制御2004

    • Author(s)
      館農 勝, 橋本 恵理 他
    • Journal Title

      アルコールと医学生物学 24

      Pages: 61-65

    • NAID

      10013456330

    • Related Report
      2004 Annual Research Report
  • [Book] 新現代精神医学文庫 アルコール性障害2006

    • Author(s)
      齋藤利和
    • Total Pages
      124
    • Publisher
      新興医学出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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