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. 2007 Mar;25(3):675-85.
doi: 10.1016/j.nbd.2006.11.006. Epub 2006 Dec 22.

A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression

Silvana Franceschetti  1 , Giulio Sancini, Andrea Buzzi, Silvia Zucchini, Beatrice Paradiso, Giuseppina Magnaghi, Carolina Frassoni, Maia Chikhladze, Giuliano Avanzini, Michele Simonato
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A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression

Silvana Franceschetti et al. Neurobiol Dis. 2007 Mar.

Abstract

Unverricht-Lundborg disease (EPM1), the most common progressive myoclonic epilepsy, is associated with a defect of cystatin B (CSTB), a protease inhibitor. We used CSTB knockout mice to test the hypothesis that EPM1 onset is related to a latent hyperexcitability and that progression depends on higher susceptibility to seizure-induced cell damage. Hippocampal slices prepared from CSTB-deficient mice were hyperexcitable, as they responded to afferent stimuli in CA1 with multiple population spikes and kainate perfusion provoked the appearance of epileptic-like activity earlier than in WT mice. This hyperexcitability may depend on loss of inhibition, because the density of GABA-immunoreactive cells was reduced in the hippocampus of CSTB knockouts. In vivo, CSTB-deficient mice treated with kainate displayed increased susceptibility to seizures, with shorter latency to seizure onset and increased seizure severity compared with WT littermates. Furthermore, a greater degree of neuronal damage was observed in CSTB-deficient than in WT mice after seizures of identical grade, indicating increased susceptibility to seizure-induced cell death.

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