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Possible role of hyperpolarization-activated cation (HCN) channels in the generation of absence seizures.

Research Project

Project/Area Number 15591140
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNippon Medical School

Principal Investigator

MARU Eiichi  Nippon Medical School, Associate Professor, 医学部, 助教授 (80221597)

Co-Investigator(Kenkyū-buntansha) YAMAGATA Kanato  Tokyo Metropolitan Institute for Neuroscience, Director of Neuropharmacology Department, 東京都神経科学総合研究所・神経薬理学, 副参事研究員 (20263262)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsAbsence epileptic seizures / hyperpolarization-activated cation channels / HCN2 subunit / ZD7288 / spike and wave discharge(SWD) / spontaneously epileptic rat(SER) / γ-butyrolactone / kindling / 欠神発作 / 遺伝性てんかんラット / SER / spike and wave discharge / 免疫染色法 / ラット / γ-hydroxybutyric acid
Research Abstract

Absence seizure, a form of idiopathic generalized epilepsy, is characterized by a brief loss of consciousness (behavioral arrest) associated with EEG recordings of spike and wave discharges(SWDs). Previous studies have demonstrated that the rhythmic bursting activity produced by the thalamocortical neural network is critical for the generation of SWD characteristic of absence epilepsy. Because HCN2, a subunit of the hyperpolarization-activatied cation (HCN) channel, -deficient mice exhibit spontaneous absence seizures, we examined the possible role of HCN channels in the generation of absence seizures in the following 3 experiments.
1.Intracerebroventricularly administered ZD7288 (more than 500 μM, 4 μL), a HCN channel blocker, induce behaviorally sudden arrests and SWDs frequently in normal Wistar-strain rats. ZD7288-induced epileptic EEG patterns were quite similar to the SWDs and sustained rhythmic slow waves induced by γ-butyrolactone (GBL).
2.Effects of the HCN channel blocker on the strength of partial epileptic seizures was examined in the amygdala kindled rat, a well-known animal model of partial epilepsy. ZD7288 (500 μM,4 μL) had no significant effects on the duration of afterdischarge in amygdala kindled rats, when injected intracerebroventriclularly 30 min previously.
3.The expression of HCN2 protein was examined immunochemically in the thalamus of spontaneously epileptic rats(SER), double mutants (zi/zi and tm/tm) showing absence-like seizures. HCN2 protein expression was significantly lower in the thalamus of SERs than in that of Wistar control rats.
When absence seizures were induced by GBL in non-epileptic Wistar rats, the expression of HCN2 was significantly up-regulated in the thalamus 2-3 days after the absence seizures.
These results indicate that HCN channels prevent intrinsically the generation of absence seizures, and its expression in the thalamic nuclei is dynamically regulated by seizure acivities.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (5 results)

All 2004 2003 Other

All Journal Article (4 results) Publications (1 results)

  • [Journal Article] てんかんの病態生理 -抑制から発作へ-2004

    • Author(s)
      丸 栄一
    • Journal Title

      神経研究の進歩 48

      Pages: 917-927

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epileptic seizures generated by GABA-mediated synaptic transmission.2004

    • Author(s)
      Eiichi Maru
    • Journal Title

      Advances in Neurological Sciences (in Japanese) 48(6)

      Pages: 917-927

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] てんかんの病態生理-抑制から発作へ-2004

    • Author(s)
      丸 栄一
    • Journal Title

      神経研究の進歩 48(6)

      Pages: 917-927

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inducible brain COX-2 facilitates the recurrence of hippocampal seizures in mouse rapid kindling.2003

    • Author(s)
      Takako Takemiya
    • Journal Title

      Prostaglandins & other Lipid Mediators 71

      Pages: 205-216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Takemiya, T., et al.: "Induciblle brain COX-2 facilitates the recurrence of hippocampal seizures in mouse rapid kindling."Prostaglandins & other Lipid Mediators. 71. 205-216 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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