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Spinal nerve defects induced by prenatal valproic acid exposure

Research Project

Project/Area Number 26461634
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionThe University of Tokushima

Principal Investigator

FUKUI Yoshihiro  徳島大学, 大学院医歯薬学研究部(医学系), 教授 (50144168)

Co-Investigator(Kenkyū-buntansha) 坂田 ひろみ  金沢医科大学, 医学部, 准教授 (50294666)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords抗てんかん薬 / バルプロ酸 / 脊髄神経 / 発達障害 / 神経管閉鎖不全 / 葉酸 / ホールマウント免疫染色
Outline of Final Research Achievements

We examined effects of prenatal exposure to valproic acid (VPA) on the development of the nervous system. VPA (100-400 mg/kg) was subcutaneously injected to pregnant ICR mice on gestational day (GD) 6, 7, 8, or 9. And their embryos were collected on GD 10. The whole-mount immunostaining using an anti-neurofilament antibody clearly identified nerve fiber bundles and dorsal ganglia consisting of spinal nerves. The incidence of these spinal nerve defects (SNDs) was significantly increased in the embryos exposed to VPA on GD 8. The incidence of SNDs caused by VPA administration was increased in a dose dependent manner Folic acid supplementation (3 mg/kg/day) during GD 6-10 reduced the incidence of VPA-induced neural tube defects (NTDs), but not SNDs. Thus, NTDs and SNDs after prenatal VPA-exposure might be induced by different mechanisms.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] A 5HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, mitigates developmental neurotoxicity of ethanol to serotonergic neurons2016

    • Author(s)
      Tsukasa Ishiguro, Hiromi Sakata-Haga, Yoshihiro Fukui
    • Journal Title

      Congenital Anomalies

      Volume: 56 Pages: 163-171

    • NAID

      130008079164

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Spinal nerve defects in mouse embryos prenatally exposed to valproic acid2016

    • Author(s)
      Bold J, Sakata-Haga H, Fukui Y
    • Journal Title

      Anat Sci Int

      Volume: 0 Issue: 1 Pages: 1-7

    • DOI

      10.1007/s12565-016-0363-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Postnatal Change in Sulcal Length Asymmetry in Cerebrum of Cynomolgus Monkeys (Macaca fascicularis)2014

    • Author(s)
      Sakamoto K, Sawada K, Fukunishi K, Imai N, Sakata-Haga H, Fukui Y
    • Journal Title

      Anatomical Record (Hoboken)

      Volume: 297(2) Issue: 2 Pages: 200-207

    • DOI

      10.1002/ar.22847

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] バルプロ酸が脊髄神経の形成に及ぼす影響2016

    • Author(s)
      坂田ひろみ、Bold Juramt、福井義浩、島田ひろき、八田稔久
    • Organizer
      日本解剖学会 第76回中部支部学術集会
    • Place of Presentation
      信州大学(長野県・松本市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胎生期バルプロ酸曝露による脊髄神経の形成異常2015

    • Author(s)
      坂田ひろみ、ボルド・ジュラムト、浅井佑介、澤田直樹、福井義浩
    • Organizer
      第55回日本先天異常学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-07-25
    • Related Report
      2015 Research-status Report 2014 Research-status Report
  • [Presentation] 胎生期エタノール曝露がもたらす中枢神経系の発達障害2015

    • Author(s)
      坂田ひろみ、福井義浩
    • Organizer
      第55回日本先天異常学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-07-25
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Abnormal running of spinal nerve fibers in mice induced by prenatal valproic acid exposure2015

    • Author(s)
      Juramt Bold, Hiromi Sakata-Haga, Yoshihiro Fukui
    • Organizer
      脳科学クラスターリトリート
    • Place of Presentation
      徳島大学(徳島県徳島市)
    • Year and Date
      2015-01-31
    • Related Report
      2014 Research-status Report
  • [Presentation] 母仔分離のタイミングが成熟後の脂肪蓄積に与える影響2014

    • Author(s)
      澤田直樹、坂田ひろみ、福井義浩
    • Organizer
      第54回日本先天異常学会学術集会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Year and Date
      2014-07-26 – 2014-07-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 胎生期フェニトイン曝露が神経系の発達に及ぼす影響2014

    • Author(s)
      坂田ひろみ、白井尚弘、福西克弘、福井義浩
    • Organizer
      第54回日本先天異常学会学術集会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Year and Date
      2014-07-26 – 2014-07-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 2a/2c receptor agonist prevents reduction of serotonergic neurons in raphe nuclei of rat offspring caused by maternal ethanol intake2014

    • Author(s)
      Yoshihiro Fukui, Tsukasa Ishiguro, Hiromi Sakata-Haga
    • Organizer
      9th the FENS Forum Neuroscience 2014
    • Place of Presentation
      Milan(Italy)
    • Year and Date
      2014-07-06 – 2014-07-09
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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