Viral clostridial light chain gene-based control of penicillin-induced neocortical seizures. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Molecular Therapy Année : 2007

Viral clostridial light chain gene-based control of penicillin-induced neocortical seizures.

Résumé

Restraining excitatory neurotransmission within a seizure focus provides a nondestructive treatment strategy for intractable neocortical epilepsy. Clostridial toxin light chain (LC) inhibits synaptic transmission by digesting a critical vesicle-docking protein, synaptobrevin, without directly altering neuronal health. This study tests the treatment efficacy of adenoviral vector delivered LC (AdLC) on a model of seizures in rats induced by motor cortex penicillin (PCN) injection. LC expression significantly reduced electroencephalogram (EEG) frequency, amplitude, duration, and latency compared to control groups injected with either an adenoviral vector bearing green fluorescent protein (AdGFP) or phosphate buffered solution (PBS). Correspondingly, LC gene expression improved behavioral manifestations including seizure severity and latency. There was no statistical difference in motor function before and after vector administration between treatment and control groups. Histological analysis revealed spatially discrete LC expression with corresponding synaptobrevin depletion in the cortex surrounding the injection site. Thus, vector-mediated LC gene delivery is capable of improving both the EEG and behavioral manifestations of PCN-induced focal neocortical seizures through synaptobrevin depletion.

Dates et versions

inserm-00383828 , version 1 (13-05-2009)

Identifiants

Citer

Jun Yang, Qingshan Teng, Thais Federici, Imad Najm, Stephan J. Chabardes, et al.. Viral clostridial light chain gene-based control of penicillin-induced neocortical seizures.. Molecular Therapy, 2007, 15 (3), pp.542-51. ⟨10.1038/sj.mt.6300069⟩. ⟨inserm-00383828⟩

Collections

INSERM
62 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More