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].
|Citazione:||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].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Titolo:||A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression|
|Autori:||Franceschetti, S; Sancini, G; Buzzi, A; Zucchini, S; Paradiso, B; Magnaghi, G; Frassoni, C; Chikhladze, M; Avanzini, G; Simonato, M|
|Data di pubblicazione:||2007|
|Rivista:||NEUROBIOLOGY OF DISEASE|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.nbd.2006.11.006|
|Appare nelle tipologie:||01 - Articolo su rivista|