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Impact of epileptic seizures on developing brain: a study using forebrain-specific Cdk5 conditional knockout mice

Research Project

Project/Area Number 22591118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionAsahikawa Medical College

Principal Investigator

TAKAHASHI Satoru  旭川医科大学, 医学部, 講師 (10431404)

Project Period (FY) 2010-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsてんかん / けいれん / 神経変性 / 炎症 / 皮質形成異常 / Cdk5 / 脳・神経 / モデル動物 / cyclin-dependent kinase 5 / 脳形成異常 / 神経細胞移動 / ノックアウトマウス / tissue-type plasminogen activator
Research Abstract

Neuronal migration disorders are often identified in patients with epilepsy refractory to medical treatment. The prolonged or repeated seizures are known to cause neuronal death; however, the mechanism remains to be elucidated. The objective of this study is to elucidate the impact of epileptic seizures on the developing brain using forebrain-specific Cdk5 knockout (Cdk5cKO) mice which show neuronal migration defects and seizures. The forebrain of the mice showed neurodegenerative changes accompanied by neuronal loss and microglial activation. Treatment with PPAR-gamma agonist pioglitazone ameliorated gliosis and neuronal loss in Cdk5cKO mice, suggesting that inflammation contributes to the pathogenesis of the seizure-induced neuronal death. This study may provide impetus for considering the development of anti-inflammatory therapies that can be used to avoid the progressive decline of neuronal function in patients with neuronal migration disorders and epilepsy.

Report

(4 results)
  • 2013 Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (8 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (4 results)

  • [Journal Article] Suppression of neuroinflammation in forebrain-specific Cdk5 conditional knockout mice by PPAR-gamma agonist improves neuronal loss and early lethality.2014

    • Author(s)
      Utreras E, Hamada R, Prochazkova M, Terse A, Takahashi S, Ohshima T, Kulkarni AB
    • Journal Title

      J Neuroinflammation

      Volume: in press Issue: 1

    • DOI

      10.1186/1742-2094-11-28

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypomyelination Phenotype Caused by Impaired Differentiation of Oligodendrocytes in Emx1-cre Mediated Cdk5 Conditional Knockout Mice2011

    • Author(s)
      He X, Takahashi S, Suzuki H, Hashikawa T, Kulkarni AB, Mikoshiba K, Ohshima T
    • Journal Title

      Neurochem Res

      Volume: 36(7) Issue: 7 Pages: 1293-1303

    • DOI

      10.1007/s11064-010-0391-0

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypomyelination Phenotype caused by impaired differentiation of oligodendrocytes in Emxl-cre mediated Cdk5 conditional knockout mice.2011

    • Author(s)
      Xe H, Takahashi S, Suzuki H, Hashikawa T, Kulkarni AB, Mikoshiba K, Ohshima T
    • Journal Title

      Neurochemical Research

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of P27Kipl at Thr187 by Cyclin-dependent Kinase 5 Modulates Neural Stem Cell Differentiation.2010

    • Author(s)
      Zheng YL, Li BS, Rudrabhatla P, Shuk la V, Amin ND, Maric D, Kesavapany S, Kanungo 」, Pareek TK, Takahashi S, Grant P, Kulkarni AB, Pant HC
    • Journal Title

      Molecular Biology of the Cell

      Volume: Vol.21 Pages: 3601-3614

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] PPARg agonist treatment of neurodegeneration in Cyclin-dependent kinase 5 conditional KO mice2013

    • Author(s)
      Hamada R, Takahashi S, Kulkarni AB, Ohshima T
    • Organizer
      Neuro
    • Related Report
      2013 Final Research Report
  • [Presentation] Inhibition of tissue-type plasminogen activator expression does not ameliorate neuro-inflammation in forebrain-specific Cdk5 conditional knockout mice2012

    • Author(s)
      Utreras E, Prochazkova M, Terse A, Takahashi S, Kulkarni AB
    • Organizer
      Society for Neuroscience Annual Meeting
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Inhibition of tissue-type plasminogen activator expression does not ameliorate neuro-inflammation in forebrain-specific Cdk5 conditional knockout mice.2012

    • Author(s)
      Utreras E, Prochazkova M, Terse A, Takahashi S, Kulkarni AB
    • Organizer
      Society for Neuroscience Annual Meeting
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] PPARg agonist treatment of neurodegeneration in Cyclin-dependent kinase 5 conditional KO mice

    • Author(s)
      Hamada R, Takahashi S, Kulkarni AB, Ohshima T
    • Organizer
      Neuro 2013(第36回日本神経科学大会、第56回日本神経化学会大会、第23回日本神経回路学会大会 合同大会)
    • Place of Presentation
      京都市
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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