Epileptogenesis in Mesial Temporal Lobe Epilepsy

• Project/Area Number: 15K06751
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Niigata 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: ¥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.

Research Products

• [Journal Article] Pathophysiological characteristics of the subiculum 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
  • Peer Reviewed / Open Access
• [Journal Article] Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy. (2018)
  • 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: Am J Hum Genet Volume: 102 Pages: 321-329
  • DOI: 10.1016/j.ajhg.2018.01.004
  • Peer Reviewed / Open Access
• [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: 82 Pages: 842-846
  • DOI: 10.1093/neuros/nyx314
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed
• [Journal Article] Ca2+ -permeable 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 Pages: 59-63
  • DOI: 10.1111/epi.13700
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Characteristic expression of p57/Kip2 in 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 Pages: 000-000
  • DOI: 10.1111/neup.12199
  • 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
  • Peer Reviewed
• [Journal Article] Somatic Mutations in MTOR Cause Focal cortical dysplasia Type IIb (2015)
  • 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 Pages: 375-386
  • DOI: 10.1002/ana.24444
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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
• [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
• [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
  • 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
• [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
• [Presentation] Epileptogenesis in mesial temporal lobe epilepsy: Physiological and Histological features (2015)
  • 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
• [Book] Epilepsy (2016)
  • 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
• [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