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Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model

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  • N. Lozovaya

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon
    INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette
    University Paris Descartes, CEA, Gif sur Yvette)

  • S. Gataullina

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon
    INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette
    University Paris Descartes, CEA, Gif sur Yvette)

  • T. Tsintsadze

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • V. Tsintsadze

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • E. Pallesi-Pocachard

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • M. Minlebaev

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon
    Laboratory of Neurobiology, Kazan Federal University)

  • N. A. Goriounova

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • E. Buhler

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • F. Watrin

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • S. Shityakov

    (University of Würzburg)

  • A. J. Becker

    (University of Bonn Medical Center)

  • A. Bordey

    (Neurosurgery, Yale University School of Medicine)

  • M. Milh

    (APHM, CHU Timone)

  • D. Scavarda

    (APHM, CHU Timone)

  • C. Bulteau

    (INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette
    University Paris Descartes, CEA, Gif sur Yvette
    Foundation Rothschild)

  • G. Dorfmuller

    (INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette
    University Paris Descartes, CEA, Gif sur Yvette
    Foundation Rothschild)

  • O. Delalande

    (Foundation Rothschild)

  • A. Represa

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • C. Cardoso

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • O. Dulac

    (INSERM U1129; University Paris Descartes, CEA, Gif sur Yvette
    University Paris Descartes, CEA, Gif sur Yvette
    Foundation Rothschild
    APHP, Necker Hospital)

  • Y. Ben-Ari

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

  • N. Burnashev

    (INSERM U901, INMED, Parc Scientifique et Technologique de Luminy 163
    UMR901, Aix-Marseille University, 58 Boulevard Charles Livon)

Abstract

Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1+/− mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (

Suggested Citation

  • N. Lozovaya & S. Gataullina & T. Tsintsadze & V. Tsintsadze & E. Pallesi-Pocachard & M. Minlebaev & N. A. Goriounova & E. Buhler & F. Watrin & S. Shityakov & A. J. Becker & A. Bordey & M. Milh & D. Sc, 2014. "Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5563
    DOI: 10.1038/ncomms5563
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    Cited by:

    1. Vasiliki Karalis & Franklin Caval-Holme & Helen S. Bateup, 2022. "Raptor downregulation rescues neuronal phenotypes in mouse models of Tuberous Sclerosis Complex," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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