| First Author | Franceschetti S | Year | 2007 |
| Journal | Neurobiol Dis | Volume | 25 |
| Issue | 3 | Pages | 675-85 |
| PubMed ID | 17188503 | Mgi Jnum | J:119089 |
| Mgi Id | MGI:3701161 | Doi | 10.1016/j.nbd.2006.11.006 |
| Citation | Franceschetti S, et al. (2007) A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression. Neurobiol Dis 25(3):675-85 |
| abstractText | 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. |
