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The role of 17beta-estradiol on pilocarpine-induced epilepsy and the downregulation of hippocampal membrane GluR2 and HCN1 channel protein levels in ovariectomized mice

Research Project

Project/Area Number 25430070
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOhu University

Principal Investigator

SEKI Kenjiro  奥羽大学, 薬学部, 講師 (50342803)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsシナプス可塑性 / 脳神経疾患 / 興奮性-抑制性神経バランス / 精神疾患 / 月経随伴性てんかん発作 / エストロゲン / 海馬 / ピロカルピン / HCN1チャネル / AMPA-GluR2 / てんかん発作 / AMPA受容体 / シグナル伝達系 / HCNチャネル / GluR2 / 細胞内トラフィッキング / マウス
Outline of Final Research Achievements

Estrogen is thought to be a risk factor for catamenial epilepsy E2 significantly increased seizure severity. In this study, we found that the E2 prolonged the latency to status epilepticus (SE) and reduced mortality. Pilocarpine-induced epilepsy reduced the protein level of the AMPA receptor GluR2 subunit at the plasma membrane. However, E2 suppressed this reduction in GluR2 and inhibited Ser880 phosphorylation during epilepsy. Next, we attempted to block GluR2-lacking AMPA receptors via intraventricular administration of 1-Naphthylacetyl spermine (Naspm) to mimic the effects of E2 treatment in freely moving mice. Treatment of Naspm after pilocarpine injection at 3 min, the latency to SE was increased and mortality was reduced. This timing of the effects of Naspm is consistent with the onset of the GluR2 phosphorylation. These results suggest that E2 promotes survival by inhibiting the GluR2 internalization.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (3 results)

All 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results) Presentation (1 results)

  • [Journal Article] Lipopolysaccharide-induced depressive-like behavior is associated with α1-adrenoceptor dependent downregulation of the membrane GluR1 subunit in the mouse medial prefrontal cortex and ventral tegmental area.2014

    • Author(s)
      Miyu Sekio, Kenjiro Seki
    • Journal Title

      International Journal of Neuropsychopharmacology

      Volume: 18(1) Issue: 1 Pages: 1-12

    • DOI

      10.1093/ijnp/pyu005

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Exendin-4 promotes the membrane trafficking of the AMPA receptor GluR1 subunit and ADAM10 in the mouse neocortex.2014

    • Author(s)
      Nobuaki Ohtake, Mieko Saito, Masaaki Eto, Kenjiro Seki
    • Journal Title

      Regulatory Peptides

      Volume: 190-191C Pages: 1-11

    • DOI

      10.1016/j.regpep.2014.04.003

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 17β-estradiolによるマウス海馬 GluR2 サブユニットのセリン残基(S880)のリン酸化阻害及び internalization 阻害作用とてんかん重積発作後の生存率上昇効果に関する研究2014

    • Author(s)
      関健二郎、大竹伸知、飯塚有紀
    • Organizer
      日本薬理学会
    • Place of Presentation
      仙台国際センター
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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