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Epileptogenesis in Mesial Temporal Lobe Epilepsy

Research Project

Project/Area Number 15K06751
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionNiigata University

Principal Investigator

Kitaura Hiroki  新潟大学, 脳研究所, 助教 (80401769)

Co-Investigator(Kenkyū-buntansha) 柿田 明美  新潟大学, 脳研究所, 教授 (80281012)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsてんかん / 海馬 / 海馬硬化症 / Kir4.1 / アストロサイト / ヒト脳スライス標本 / 苔状線維 / 海馬支脚 / 海馬硬化 / 脳スライス / イメージング
Outline of Final Research Achievements

The majority of seizures originate primarily from the hippocampus in patient of Mesial temporal lobe epilepsy (MTLE). The resected hippocampal tissue often shows severe neuronal loss, a condition referred to as hippocampal sclerosis. Here we investigated epileptiform activities ex vivo using living hippocampal tissue taken from patients with MTLE. Flavoprotein fluorescence imaging and local field potential recordings revealed that epileptiform activities developed from the subiculum. Moreover, physiological and morphological experiments revealed possible impairment of K+ clearance in the subiculum affected by HS. Stimulation of mossy fibers induced recurrent trans-synaptic activity in the granule cell layer of the dentate gyrus, suggesting that mossy fiber sprouting in HS also contributes to the epileptogenic mechanism. These results indicate that pathophysiological alterations involving the subiculum and dentate gyrus could be responsible for epileptogenesis in patients with MTLE.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (6 results) (of which Invited: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Pathophysiological characteristics associated with epileptogenesis in Human Hippocampal sclerosis.2018

    • Author(s)
      Kitaura H, Shirozu H, Masuda H, Fukuda M, Fujii Y, Kakita A
    • Journal Title

      EBioMedicine

      Volume: 29 Pages: 38-46

    • DOI

      10.1016/j.ebiom.2018.02.013

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biallelic Variants in CNPY3 , Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy2018

    • Author(s)
      Mutoh Hiroki、Kato Mitsuhiro、Akita Tenpei、Shibata Takuma、Wakamoto Hiroyuki、Ikeda Hiroko、Kitaura Hiroki、Aoto Kazushi、Nakashima Mitsuko、Wang Tianying、Ohba Chihiro、Miyatake Satoko、Miyake Noriko、Kakita Akiyoshi、Miyake Kensuke、Fukuda Atsuo、Matsumoto Naomichi、Saitsu Hirotomo
    • Journal Title

      The American Journal of Human Genetics

      Volume: 102 Issue: 2 Pages: 321-329

    • DOI

      10.1016/j.ajhg.2018.01.004

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aquaporin PET differentiates between grade III and IV human astrocytoma.2018

    • Author(s)
      Suzuki Y, Nakamura Y, Yamada K, Kurabe S, Okamoto K, Aoki H, Kitaura H, Kakita A, Fujii Y, Huber VJ, Igarashi H, Kwee IL, Nakada T
    • Journal Title

      Neurosurgery

      Volume: 印刷中 Issue: 6 Pages: 842-846

    • DOI

      10.1093/neuros/nyx314

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Features of amygdala in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An MRI volumetric and histopathological study.2017

    • Author(s)
      Nakayama Y, Masuda H, Shirozu H, Ito Y, Higashijima T, Kitaura H, Fujii Y, Kakita A, Fukuda M.
    • Journal Title

      Epilepsy Res

      Volume: 135 Pages: 50-55

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca2+-permiable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma.2017

    • Author(s)
      Kitaura H, Sonoda M, Teramoto S, Shirozu H, Shimizu H, Kimura M, Masuda H, Ito Y, Takahashi H, Kwak S, Kameyama S, Kakita A.
    • Journal Title

      Epilepsia

      Volume: 58 Issue: 4 Pages: 59-63

    • DOI

      10.1111/epi.13700

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Characteristic p57/Kip2 immunoreactivity of balloon cells in focal cortical dysplasia.2015

    • Author(s)
      Kimura T, Kitaura H, Masuda H, Kameyama S, Saito Y, Otsuki T, Nakazawa A, Morota N, Yamamoto T, Iida K, Takahashi H, Kakita A.
    • Journal Title

      Neuropathology

      Volume: 00 Issue: 5 Pages: 000-000

    • DOI

      10.1111/neup.12199

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] フラビン蛍光イメージングによるてんかん原性の解析2015

    • Author(s)
      北浦弘樹、柿田明美
    • Journal Title

      Epilepsy

      Volume: 19 Pages: 4-5

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb2015

    • Author(s)
      Nakashima M, Saitsu H, Takei N, Tohyama J, Kato M, Kitaura H, Shiina M, Shirozu H, Masuda H, Watanabe K, Ohba C, Tsurusaki Y, Miyake N, Zheng Y, Sato T, Takebayashi H, Ogata K, Kameyama S, Kakita A, Matsumoto N
    • Journal Title

      Ann. Neurol.

      Volume: 78 Issue: 3 Pages: 375-386

    • DOI

      10.1002/ana.24444

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 海馬硬化症におけるてんかん原性の病態生理学的解析2017

    • Author(s)
      北浦弘樹
    • Organizer
      第40回日本てんかん外科学会
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Presentation] 海馬硬化症の病態病理2017

    • Author(s)
      北浦弘樹
    • Organizer
      第58回日本神経病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] グリア細胞のてんかん原性2017

    • Author(s)
      北浦弘樹
    • Organizer
      第51回日本てんかん学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 海綿状血管腫におけるヘモジデリン沈着とてんかん原性の検討2016

    • Author(s)
      北浦弘樹
    • Organizer
      第57回日本神経病理学会
    • Place of Presentation
      ホテルニューキャッスル(青森県弘前市)
    • Year and Date
      2016-06-01
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト脳スライス標本を用いたてんかん病巣のイメージング解析2016

    • Author(s)
      北浦弘樹
    • Organizer
      第5回 新潟脳研-生理研合同シンポジウム
    • Place of Presentation
      生理学研究所・愛知県岡崎市
    • Year and Date
      2016-03-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Epileptogenesis in mesial temporal lobe epilepsy: Physiological and Histological features2015

    • Author(s)
      北浦弘樹
    • Organizer
      第56回日本神経病理学会総会学術研究会
    • Place of Presentation
      九州大学百年講堂・福岡県福岡市
    • Year and Date
      2015-06-03
    • Related Report
      2015 Research-status Report
  • [Book] Epilepsy2016

    • Author(s)
      北浦弘樹、武井延之、中島光子、松本直通、柿田明美
    • Total Pages
      6
    • Publisher
      メディカルレビュー
    • Related Report
      2016 Research-status Report
  • [Remarks] 研究成果:側頭葉てんかんの新たな発症メカニズムを解明しました

    • URL

      http://www.bri.niigata-u.ac.jp/result/path/000988.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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