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Molecular biological approach to explore the cause of brain damage after prenatal ethanol exposure

Research Project

Project/Area Number 16390310
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

FUKUI Yoshihiro  The University of Tokushima, Graduate School Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (50144168)

Co-Investigator(Kenkyū-buntansha) SAWADA Kazuhiko  The University of Tokushima, Graduate School Institute of Health Biosciences, Associate Professor, 大学院ヘルスバイオサイエンス研究部, 助教授 (10284324)
SAKATA Hiromi (HAGA Hiromi)  The University of Tokushima, Gradate School Institute of Health Biosciences, Assistant Professor, 大学院ヘルスバイオサイエンス研究部, 講師 (50294666)
IMAGAWA Tomohiro  The University of Tokushima, School of Medecine, Associate Professor, 医学部, 助教授 (20232605)
MIKI Takanori  The University of Tokushima, School of Medecine, Associate Professor, 医学部, 助教授 (30274294)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
Keywordsfetal alcohol syndrome / serotonin / BDNF / NGF / astrocyte / NFG / チロシン水酸化酵素 / FGF8 / TGFβ / GFAP / ビメンチン / Fetal alcohol syndrome / Dopamine / Serotonin / Shh / Hippocampus / Pyramidal cell
Research Abstract

To identify genes and factors which are responsible for brain alterations after prenatal ethanol exposure, we examined expression of genes and determination of neurotransmitters or neurotrophic factors in ethanol-exposed rat brains. Immunohistochemical study using anti-5-HT antibody revealed that prenatal ethanol exposure resulted in a reduction in the number and defects of migration of serotonin-positive neurons in the dorsal and medial raphe nuclei of rat fetuses. In ethanol-exposed rat fetuses, amounts of both 5-HT and its metabolite (5-HIAA) were decreased as well. RT-PCR analysis revealed a reduction of sonic hedgehog (Shh) expression in the brains of ethanol-exposed rat fetuses. Because Shh is related to the fate of 5-HT neuron, we concluded that prenatal exposure to ethanol impairs the development of 5-HT neurons, and this might have resulted in the reduction of Shh expressions. Therefore, the reduction of 5-HT neurons seen in the raphe persisted into adulthood, and prenatal ethanol-exposed rats showed anxiety-like behavior. In ethanol-exposed rat cerebellum, BDNF mRNA was decreased but NGF and its receptor (Trk A) mRNA expression were increased. Also, reduction of OMgp and GDNF mRNA expression was observed in the hippocampus and the septum nucleus, respectively. Thus, it is established that ethanol can affect expression of certain neurotrophic factors and their receptors. We monitored the intracellular calcium concentration after glutamate stimulation in ethanol-treated astrocytes derived from the hippocampus of neonatal rat (Day 3), and revealed that the glutamate-reactive cell number was decreased compared to non-ethanol-treated astrocytes. Since the calcium concentration in astrocytes might be related to maturation of synapse, the result suggests that ethanol may affect development of the neural circuit via a calcium signaling cascade in astrocytes.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (24 results)

All 2006 2005 2004

All Journal Article (23 results) Book (1 results)

  • [Journal Article] Alterations in circadian rhythm phase shifting ability in rats following ethanol exposure during the third trimester brain growth spurt2006

    • Author(s)
      Sakata-Haga H, et al.
    • Journal Title

      Alcoholism : Clinical and Experimental Research 30

      Pages: 899-907

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Oligodendrocyte myelin glycoprotein (OMgp) in rat hippocampus is depleted by chronic ethanol consumption.2006

    • Author(s)
      Okamoto H, et al.
    • Journal Title

      Neurosci Lett. 406

      Pages: 76-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of chronic ethanol administration on the expression levels of neurotrophic factors in the rat hippocampus.2006

    • Author(s)
      Okamoto H, et al.
    • Journal Title

      Okajimas Folia Anat Jpn. 83

      Pages: 1-6

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Alterations in circadian rhythm phase shifting ability in rats following ethanol exposure during the third trimester brain growth spurt2006

    • Author(s)
      Sakata-Haga H et al.
    • Journal Title

      Alcoholism : Clinical and Experimental Research 30

      Pages: 899-907

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oligodendrocyte myelin glycoprotein(OMgp)in rat hippocampus is depleted by chronic ethanolconsumption.2006

    • Author(s)
      Okamoto H, et al.
    • Journal Title

      Neurosci Lett 406

      Pages: 76-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of chronic ethanol administration on the expression levels of neurotrophic factors in the rat hippocampus.2006

    • Author(s)
      Okamoto H, et al.
    • Journal Title

      Okajimas Falia Anat Jpn. 83

      Pages: 1-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Morphological study on the inferior olivary nuclear complex of the donkey (Equus asinus)2006

    • Author(s)
      RASHED R, et al.
    • Journal Title

      Tisssue and Cell 38

      Pages: 353-359

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Interaction between glycogen body cell and neuron : examination in co-culture system2006

    • Author(s)
      Imagawa T, et al.
    • Journal Title

      Journal of Veterinary Medical Science 68(in press)

    • NAID

      110004820612

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of lactate dehydrogenase-A and-B mRNAs in chick glycogen body.2006

    • Author(s)
      Imagawa T, et al.
    • Journal Title

      Poultry Science 85

      Pages: 1232-1238

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions2006

    • Author(s)
      Teraoka H, et al.
    • Journal Title

      Toxicology and Applied Pharmacology 212

      Pages: 24-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Oligodendrocyte myelin glycoprotein(OMgp)in rat hippocampus is depleted by chronic ethanolconsumption.2006

    • Author(s)
      Okamoto H, et al.
    • Journal Title

      Neurosci Lett. 406

      Pages: 76-80

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of chronic ethanol administration on the expression levels of neurotrophic factors in the rat hippocampus.2006

    • Author(s)
      Okamoto H, et al.
    • Journal Title

      Okajimas Folia Anat Jpan. 83

      Pages: 1-6

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Morphological study on the inferior olivary nuclear complex of the donkey (Equusasinus)2006

    • Author(s)
      RASHED R, et al.
    • Journal Title

      Tissue and Cell 38

      Pages: 353-359

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interaction between glycogen body cell and neuron : examination in co-culture system2006

    • Author(s)
      Imagawa T, et al.
    • Journal Title

      Journal of Veterinary Medical Science 68

      Pages: 1081-1087

    • NAID

      110004820612

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of lactate dehydrogenase-A and -B mRNAs in chick glycogen body.2006

    • Author(s)
      Imagawa T, et al.
    • Journal Title

      Poultry Science 85

      Pages: 1232-1238

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Alterations in circadian rythm phase shifting ability in rats following ethanol exposure during thee third trimester brain growth spurt2006

    • Author(s)
      Sakata-Haga H, et al.
    • Journal Title

      Alcohol Clin Exp Res (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effects of chronic ethanol administration on the expression levels of neurotrophic factors in the rat hippocampus2006

    • Author(s)
      Hanayo O, et al.
    • Journal Title

      Okajima Folias Anatomica Japonica (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fetal alcohol effects potential treatments from basic science2005

    • Author(s)
      Consuelo guerri M Pascual, et al.
    • Journal Title

      Alcoholism Clinical and Experimental Research 29(6)

      Pages: 1074-1079

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fetal Alcohol Effects : Potential Treatment From Basic Science (proc.)2005

    • Author(s)
      Consuelo G, et al.
    • Journal Title

      Alcohol Clin Exp Res 29

      Pages: 1074-1079

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A quantitative study of the Purkinje cells in the cerebellum and the inferior olivary neurons in the chicken2005

    • Author(s)
      Rashed R, et al.
    • Journal Title

      Journal of Veterinary Medical Science 67

      Pages: 1261-1263

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hydrocephalus following prenatal exposure to ethanol2004

    • Author(s)
      Sakata-Haga H, et al.
    • Journal Title

      Acta Neuropathologica 108

      Pages: 393-398

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of age and alcohol exposure during early life on pyramidal cell numbers in the CA1-CA3 region of the rat hippocampus2004

    • Author(s)
      Miki T, et al.
    • Journal Title

      Hippocampus 14(1)

      Pages: 124-134

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of age and alcohol exposure during early life on pyramidal cell numbers in the CA1-CA3 region of the rat hippocanpus2004

    • Author(s)
      Takanori Miki, et al.
    • Journal Title

      Hippocampus 14(1)

      Pages: 124-134

    • Related Report
      2004 Annual Research Report
  • [Book] 女性とアルコール2005

    • Author(s)
      坂田 ひろみ
    • Publisher
      特定非営利活動法人 お茶の水学術事業会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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

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