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REDUCTION OF FUNCTIONAL GABA_A RECEPTOR EXPRESSION IN THE NEOCORTEX OF EL MICE

Research Project

Project/Area Number 13670681
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionUniversity of Occupational and Environmental Health

Principal Investigator

YUHI Tomoaki  University of Occupational and Environmental Health, School of Medicine, Research Associate, 医学部, 助手 (60330982)

Co-Investigator(Kenkyū-buntansha) UENO Susumu  University of Occupational and Environmental Health, School of Medicine, Research Assistant Professor, 医学部, 講師 (00279324)
FUETA Yukiko  University of Occupational and Environmental Health, School of health sciences, Research Associate, 産業保健学部, 助手 (10132482)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsEl mice / GABA_A receptor / Xenopus oocytes / gene expression / messengerRNA / neocortex slices / α1 subunit / bicuculline / EIマウス / GABA受容体
Research Abstract

There is extensive evidence indicating a crucial role for γ-aminobutyric acid (GABA) in epileptogenesis. The El (epilepsy-like) mouse is an epilepsy model developed from the ddY mouse and is very susceptible to seizure. El mice have been found to exhibit a decrease in GABA-mediated inhibition. However, previous studies remained nuclear about relationship between the GABA receptor function and epileptogenesis. In the present study, we investigated the GABA_A receptor gene expression and function in the neocortex of unstimulated El mice and ddY control mice (18-20 weeks old).
1) Northern blot analysis showed 30% decrease in GABA_A receptor α1 subunit messenger RNA (mRNA) level in El mice, compared to ddY mice. On the other hand, β2 and γ2 subunit mRNA levels did not show any significant differences.
2) GABA_A receptor functions were analyzed by the measurement of GABA-induced currents using Xenopus oocytes expression system. The maximal GABA-induced currents obtained from oocytes injected with neocortex mRNA of El mice, were significantly smaller than those obtained from oocytes injected with mRNA of ddY mice.
3) Extracellular recordings from the neocortex slices using single-pulse configuration showed significant difference in the GABA_A receptor antagonist (bicuculline: BMI and picrotoxin:PTX)-induced changes of field significant decrease in the BMI and PTX-induced changes of the amplitude of field potentials in El(-) mice.
These results suggest that, in the neocortex of El(-) mice, there is a decrease in GABA_A receptor expression and recurrent GABAergic inhibition, which may be related to the epileptogenesis in the El strain.

Report

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

    (6 results)

All Other

All Publications (6 results)

  • [Publications] T.YUHI, S.UENO, Y.FUETA, N.YANAGIHARA.T.TSUJI: "Reduction of functional GABA_A receptor expression in the neocortex of El mice"Society for neuroscience 32nd annual meeting : Neuroscience 2002 program. (CD-ROM). 433.4 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Ueno, T.Yuhi, Y.Fueta, S.Tsuji, N.Yanagihara: "Change in GABA_A receptor function in the neocortex of El mice"Neuroscience research. 26. S134 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Susumu Ueno, Tomoaki Yuhi, Yukiko Fueta, Sadatoshi Tsuji, Nobuyuki Yanagihara: "CHANGES IN GABA_A RECEPTOR FUNCTION IN THE NEOCORTEX OF EL MICE"Neuroscience research. 26. S134 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. YUHI, S. UENO, Y. FUETA, N. YANAGIHARA, T. TSUJI: "Reduction of functional GABA_A receptor expression in the neocortex of El mice"Society for neuroscience 32nd annual meeting: Neuroscience 2002 program, CD-ROM. No. 433.4. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.YUHI, S.UENO, Y.FUETA, N.YANAGIHARA, T.TSUJI: "Reduction of functional GABA_A receptor expression in the neocortex of EI mice"Society for neuroscience 32nd annual meeting : Neuroscience 2002 program. 11-11 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Ueno, T.Yuhi, Fueta, S.Tsuji, N.Yanagihara: "Change in GABA_A receptor function in the neocortex of EI mice"Neuroscience research. (In press).

    • Related Report
      2002 Annual Research Report

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

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