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The Pathophysiological Role of Neurogenesis and Neuronal Loss in the Temporal Lobe Epilepsy

Research Project

Project/Area Number 13671011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionKagawa Medical University

Principal Investigator

MORIMOTO kiyoshi  Department of Neuropsychiatry, Kagawa Medical University, Associate Professor, 医学部, 助教授 (20166432)

Co-Investigator(Kenkyū-buntansha) HIRAO toru  Department of Neuropsychiatry, Kagawa Medical University Assistant Professor, 医学部, 助手 (10314915)
WATANABE takemi  Department of Neuropsychiatry, Kagawa Medical University Assistant Professor, 医学部附属病院, 助手 (50304598)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
KeywordsTemoral lobe epilepsy / Kainate Model / Dentate granule cell neurogenesis / NMDA receptors / Neuronal Loss / カイニン酸モ
Research Abstract

To investigate the mechanism of synaptic reorganization in epileptogenesis, we studied dentate granule cell neurogenesis and neuronal loss in the rat kainate model of temporal lobe epilepsy, and their possible association with NMDA receptor activation. In rats, kainate was microinjected into the left amygdala, and limbic status epilepticus was induced. After the kainate injection, bromodeoxyuridine (BrdU) immunohistochemistry and Nissl staining were performed. In addition, MK-801, a selective NMDA receptor antagonist, was administered systemically either once or three times. Kainate-treated rats showed a marked increase in BrdU-positive cells in the bilateral dentate gyrus, while clear neuronal loss was apparent in the CA3 and CA1 regions only on the side ipsilateral to the site of kainate injection. Single pretreatment with MK-801 had no significant effect on kainate-induced enhancement of neurogenesis, whereas treatment with MK-801 three times slightly reduced it. MK-801 also showed significant protective effects against CA1 neuronal damage, but no significant protective effects against CA3 neuronal damage. These results indicate that kainate-induced focal seizure activity enhances adult neurogenesis in the dentate gyrus, which may lead to epileptogenesis independent of hippocampal neuronal damage. The seizure-induced enhancement of neurogenesis may be partly mediated via NMDA receptor activation.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 森本 清, 平尾 徹: "グルタミン酸受容体:発作発現とてんかん原性における役割"分子精神医学. 1・4. 367-374 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kodama K, Yamada N, Sato K, Sato T, Morimoto K, Kuroda S: "The insular but not the perirhinal cortex is involved in the expression of fully-kindled amygdoid seizures in rats"Epilepsy Research. 46. 169-178 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 森本 清: "てんかんの神経科学研究の現況と展望"てんかん学の最前線. 3. 1-5 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 二宮貴至, 森本 清, 渡辺岳海, 平尾徹, 安原治, 木村 浩, 洲脇 寛: "側頭葉てんかんにおける海馬歯状回顆粒細胞新生の病理学的意義-カイニン酸モデルを用いた実験的研究"てんかん研究. 21・2. 157-166 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morimoto K, Miyatake R, Nakamura M, Watanabe T, Hirao T, Suwaki H: "Delusional disorder ; Molecular genetic evidence for dopamine psychosis"Neuropsychopharmacology. 26. 794-801 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morimoto K, Miyatake R, Nakamura M: "Catecholamine Research : From Molecular Insights to Clinical Medicine"Dopamine psychosis in schizophrenia? : Molecular genetic study on delusional disorder. 4 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kodama K, Yamada N, Sato K, Sato T, Morimoto K, Kuroda S:: "The insular but not the perirhinal cortex is involved in the expression of fully-kindled amygdoid seizures in rats"Epilepsy Research. 46. 169-178 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takashi Ninomiya, Kiyoshi Morimoto, Takemi Watanabe, Tohru Hirao, Osamu Yasuhara, Hiroshi Kimura, Hiroshi Suwaki: "Status epilepticus-induced neurogenesis and neuron loss in the kainate model of temporal lobe epilepsy"Journal of Japan Epilepsy Society. 21. 157-166 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morimoto K, Miyatake R, Nakamura M, Watanabe T, Hirao T, Suwaki H:: "Delusional disorder, Molecular genetic evidence for dopamine psychosis"Neuropsychopharmacology. 26. 794-801 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morimoto K, Miyatake R, Nakamura M: Nagatsu T, Nabeshima T, McCarty R, Goldstein DS (Dds): "Dopamine psychosis in schizophrenia?: Molecular genetic study on delusional disorder. In: Catecholamin Research: From Molecular Insights of Clinical Medicine"Klumer Academic/Plenum Press. 409-412 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 森本 清, 平尾 徹: "グルタミン酸受容体:発作発現とてんかん原性における役割"分子精神医学. 1・4. 367-374 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kodama K, Yamada N, Sato K, Sato T, Morimoto K, Kuroda S: "The insular but not the perirhinal cortex is involved in the expression of fully-kindled amygdoid seizures in rats"Epilepsy Research. 46. 169-178 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森本 清: "てんかんの神経科学研究の現況と展望"てんかん学の最前線. 3. 1-5 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 二宮貴至, 森本 清, 渡辺岳海, 平尾 徹, 安原 治, 木村 宏, 洲脇 寛: "側頭葉てんかんにおける海馬歯状回顆粒細胞新生の病理学的意義-カイニン酸モデルを用いた実験的研究"てんかん研究. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 森本 清, 平尾 徹: "グルタミン酸受容体:発作発現とてんかん原性における役割"分子精神医学. 1・4. 367-374 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kodama K, Yamada N, Sato K, Sato T, Morimoto K, Kuroda S: "The insular but not the perirhinal cortex is involved in the expression of fully-kindled amygdaloid seizures in rats"Epilepsy Research. 46. 169-178 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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