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The post-genomic research for the pathophysiology and treatment of alcohol and drug addictions.

Research Project

Project/Area Number 14370292
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, Neuropsy School of Medicine, Professor, 医学部, 教授 (50128518)

Co-Investigator(Kenkyū-buntansha) SOHMA Hitoshi  Sapporo Medical Univ, Dept of Biochem School of Medicine, Assisant Professor, 医学部, 助教授 (70226702)
YAMAMOTO Megumi  Sapporo Medical Univ, Neuropsy School of Medicine, 医学部, 助手 (90347170)
OZAWA Hiroki  Nagasaki Univ, Division of Neuropsy Dept of Neurosensory Medicine, Professor, 医学部, 教授 (50260766)
KATO Tadafumi  Riken Brain Science Institute, Dept of Molecular Dynamics of Mental Disorders, Laboratory Head, 精神疾患動態研究チーム, チームリーダー (30214381)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2003: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2002: ¥8,500,000 (Direct Cost: ¥8,500,000)
KeywordsAlcohol dependence / cAMP / AnnexinIV / CREB / NE-κB / BDNF / Neurotrophic factor / Neural stem cell / アルコール依存 / c-AMP / アルコール / Ca^<2+> / Ca^<2+>-結合蛋白質 / NFκB / SH-SY5Y細胞
Research Abstract

We have previously demonstrated that the cellular cAMP-signaling is changed in blood cells in family-history positive alcoholic patients : quantitative reduction of type 1 adenylyl cyclase(AC1), ACVIII and G_<sα> mRNA. Since the cellular Ca^<2+> signaling alternation by the chronic alcohol consumption has been attended as well as cAMP signaling, we investigated the effect of alcohol on the Ca^<2+> signaling, using postmortem human brains and cultured cells. The Ca^<2+>-binding protein, annexinIV was increased in the alcoholic patients, and the level of annexinIV was increased in alcohol-treated A549 cells. The cellular downstream signaling molecule of cAMP,cAMP responsive element binding protein(CREB) helps to regulate long-term potentiation and synaptic plasticity, it is plausible that EtOH affects the CREB-induced gene transcriptions, which may affect neural differentiation/development. We focused on the mechanism of the EtOH induced cell damage and examined the role of the neurotrop … More hic factor on the effect of EtOH with neurobalstoma cells(SH-SY5Y). The cellular damage was induced by Ethanol treatment in dose-dependently. The CREB activity and the secretion of brain-derived neurotrophic factor(BDNF) which expression is regulated by CREB were both diminished in the ethanol treated SH-SY5Y cells. On the other hand, the transcriptional activity of NF-κB was activated by Ethanol. These are demonstrated that the decrased CREB-BDNF pathway impairment and NE-κB activation are involved in the mechanisms of Ethanol induced damage and neuronalplasticity change. We next investigated the effects of EtOH on neuronal differentiation in neural stem cells(NSCs). EtOH(20 to 100mM) inhibited neuronal differentiation, without affecting survival rate. The addition, of either IGF-1 or BDNF diminished inhibitory effect of EtOH on NSC differentiation. Thus, it is suggested that neurotrophic factors play important roles not only in differentiation but also defense from EtOH-induced cellular damage. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Sohma H: "Augmentation of ethanol-induced cell damages and activation of nuclear factor-kappa B by annexin IV in cultured cells."Alcohol Clin.Exp.Res.. 27. 64S-67S (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 館農 勝: "神経幹細胞の分化誘導制御に対するエタノールの影響"アルコールと医学生物学. 23. 115-120 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山本 恵: "エタノールによる脳内神経回路網改変の可能性"日本アルコール・薬物医学会雑誌. 39. 51-60 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwamoto K: "Decreased expression of PCP4/PEP19 in the prefrontal cortex of alcoholics revealed by oligonucleotide microarray analysis."Mol.Brain Res.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tateno M: "Ethanol inhibition of neural stem cell differentiation is reduced by neurotrophic factors."Alcohol Clin.Exp.Res.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 山本恵: "アルコール依存の神経生物学"Clini.Nuerosci.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 池田 官司: "単純酩酊 別冊日本臨床 領域別症候群40(精神医学症候群III-器質・症状性精神障害など-)"日本臨床社. 394-397 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohkawa H: "Ethanol induced augmentation of annexin IV in cultured cells and the enhancement of cytotoxicity by overexpression of annexin IV by ethanol."Biophim.Biophys.Acta.. 1488. 217-225 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sohma H: "Ethanol-induced augmentation of annexin IV expression in rat C6 glioma and human A549 adenocarcinoma cells."Alcohol Cli.Exp.Res.. 26. 44S-48S (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sohma H: "Augmentation of ethanol-induced cell damage and activation of nuclear factor-kappa B by annexin IV in cultured cells."Alcohol Cli.Exp.Res.. 27. 64S-67S (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tateno M: "Ethanol inhibition of neural stem cell differentiation is reduced by neurotrophic factors."Alcohol Cli.Exp.Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwamoto K: "Decreased expression of PCP4/PEP 19 in the prefrontal cortex of alcoholics revealed by oligonucleotide microarray analysis."Mol.Brain Res.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sohma H: "Augmentation of ethanol-induced cell damage and activation of nuclear factor-kappa B by annexin IV in cultured cells."Alcohol Clin.Exp.Res.. 27. 64S-67S (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 畠山佳久: "喫煙者と非喫煙者における視覚的注意過程の検討"日本アルコール・薬物医学会雑誌. 38. 341-349 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 館農 勝: "神経幹細胞の分化誘導制御に対するエタノールの影響"アルコールと医学生物学. 23. 115-120 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 山本 恵: "エタノールによる脳内神経回路網改変の可能性"日本アルコール・薬物医学会雑誌. 39. 51-60 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 齋藤利和: "アルコールの診断と治療"精神神経学雑誌. 106. 102-107 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwamoto K: "Decreased expression of PCP4/PEP19 in the prefrontal cortex of alcoholics revealed by oligonucleotide microarray analysis."Mol.Brain Res.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Tateno M: "Ethanol inhibition of neural stein cell differentiation is reduced by neurotrophic factors."Alcohol Clin.Exp.Res.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 山本 恵: "アルコール依存の神経生物学"Clini.Neurosci.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 池田官司: "別冊日本臨床 領域別症候群40 精神医学症候群III-器質・症状性精神障害など- (単純酩酊)"日本臨床社. 4 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 池田官司: "別冊日本臨床 領域別症候群40 精神医学症候群III-器質・症状性精神障害など- (アルコール幻覚症)"日本臨床社. 4 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sohma, H.: "Ethanol-induced augmentation of annexin IV expression in rat C6 glioma and human A549 adenocarcinoma cells"Alcohol. Clin. Exp. Res.. 26. 44S-48S (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohkawa, H.: "Ethanol-Induced Augmentation of Annexin IV in Cultured Cells and the Enhancement of Cytotoxicity by Overexpression of Annexin IV by Ethanol"Biochim. Biophys. Acta. 1588. 217-225 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 相馬 仁: "アルコールによる細胞内Ca^<2+>情報伝達素子の発現変化と細胞障害性"アルコールと医学生物学. 22. 4-9 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 大川 浩子: "痴呆の分子マーカー-血中に出現するカルシウム結合蛋白質アネキシンを指標にして-"老年精神医学雑誌. 14. 227-235 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 齋藤 利和: "アルコール依存症のメカニズム"月刊精神科. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 齋藤 利和: "アルコール依存症の生物学的研究とその臨床的応用"精神神経学雑誌. 104. 191-200 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 齋藤 利和: "アルコール・薬物関連障害の診断・治療ガイドライン"株式会社じほう. 237 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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