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Suppression of epileptogenesis by modification of N-methyl-d-aspartate receptor subunit composition

Authors

  • Johan Bengzon,

    1. Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden
    2. National Institute of Bioscience and Human-Technology, 1-1, Higashi, Tsukuba, Ibaraki, 305, Japan
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  • Shigeo Okabe,

    1. Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden
    2. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, 36 Convent Drive, Bethesda, MD 20892-4092, USA
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  • Olle Lindvall,

    1. Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden
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  • Ronald D. G. McKay

    1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, 36 Convent Drive, Bethesda, MD 20892-4092, USA
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Dr Johan Bengzon, as above.
E-mail: johan.bengzon@neurol.lu.se

Abstract

The effects of altered N-methyl-d-aspartate (NMDA) receptor subunit composition on seizure development in kindling epilepsy were assessed in transgenic mice expressing high neuronal levels of NR2D under control of the calcium/calmodulin kinase II alpha subunit (αCaMKII) promoter. The NR2D subunit is normally present at very low levels in the mature forebrain. Transgenic mice showed a marked reduction of amygdala kindling development. Spread of epileptic activity was retarded and generalized seizures appeared later in animals overexpressing NR2D compared with wild-type mice. The progressive lengthening of epileptiform activity, which normally occurs in kindling, was also dampened in transgenic animals. We conclude that NMDA receptor subunit composition determines the progression of experimental epilepsy.

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