title: Tetanus neurotoxin-induced epilepsy in mouse visual cortex.
abstract: Tetanus neurotoxin (TeNT) is a metalloprotease that cleaves the synaptic protein VAMP/synaptobrevin, leading to focal epilepsy. Although this model is widely used in rats, the time course and spatial specificity of TeNT proteolytic action have not been precisely defined. Here we have studied the biochemical, electrographic, and anatomic characteristics of TeNT-induced epilepsy in mouse visual cortex (V1). We found that VAMP cleavage peaked at 10 days, was reduced at 21 days, and completely extinguished 45 days following TeNT delivery. VAMP proteolysis was restricted to the injected V1 and ipsilateral thalamus, whereas it was undetectable in other cortical areas. Electrographic epileptiform activity was evident both during and after the time window of TeNT effects, indicating development of chronic epilepsy. Anatomic analyses found no evidence for long-term tissue damage, such as neuronal loss or microglia activation. These data show that TeNT reliably induces nonlesional epilepsy in mouse cortex. Due to the excellent physiologic knowledge of the visual cortex and the availability of mouse transgenic strains, this model will be useful for examining the network and cellular alterations underlying hyperexcitability within an epileptic focus.
authors.affiliation: CNR Neuroscience Institute, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mainardi
authors.forename: Marta
authors.initials: M
authors.lastname: Pietrasanta
authors.forename: Eleonora
authors.initials: E
authors.lastname: Vannini
authors.forename: Ornella
authors.initials: O
authors.lastname: Rossetto
authors.forename: Matteo
authors.initials: M
authors.lastname: Caleo
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013744:Tetanus Toxin / Q000633:toxicity*; D013997:Time Factors; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009498:Neurotoxins; D013744:Tetanus Toxin; D050988:Vesicle-Associated Membrane Protein 2; D010751:Phosphopyruvate Hydratase