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A pathogenetic hypothesis of Unverricht–Lundborg disease onset and progression
- Source :
-
Neurobiology of Disease . Mar2007, Vol. 25 Issue 3, p675-685. 11p. - Publication Year :
- 2007
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *RODENTS
*DEVELOPMENTAL disabilities
*EPILEPSY
*BRAIN diseases
Subjects
Details
- Language :
- English
- ISSN :
- 09699961
- Volume :
- 25
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Neurobiology of Disease
- Publication Type :
- Academic Journal
- Accession number :
- 24220891
- Full Text :
- https://doi.org/10.1016/j.nbd.2006.11.006