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.

Franceschetti, S., Sancini, G., Buzzi, A., Zucchini, S., Paradiso, B., Magnaghi, G., et al. (2007). A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression. NEUROBIOLOGY OF DISEASE, 25(3), 675-685 [10.1016/j.nbd.2006.11.006].

A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression

SANCINI, GIULIO ALFREDO;
2007

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.
Articolo in rivista - Articolo scientifico
Unverricht-Lundborg disease (EPM1); cystatin B (CSTB); Neurodegeneration; Epilepsy; Microglia; Excitotoxicity; EPM1
English
Franceschetti, S., Sancini, G., Buzzi, A., Zucchini, S., Paradiso, B., Magnaghi, G., et al. (2007). A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression. NEUROBIOLOGY OF DISEASE, 25(3), 675-685 [10.1016/j.nbd.2006.11.006].
Franceschetti, S; Sancini, G; Buzzi, A; Zucchini, S; Paradiso, B; Magnaghi, G; Frassoni, C; Chikhladze, M; Avanzini, G; Simonato, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/6673
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