Tetanus neurotoxin-induced epilepsy in mouse visual cortex

Epilepsia
Marco MainardiMatteo Caleo

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 epile...Continue Reading

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Citations

Jan 10, 2013·PLoS Pathogens·Laura RestaniGiampietro Schiavo
Nov 14, 2012·Science Translational Medicine·Robert C WykesDimitri M Kullmann
Mar 19, 2014·Nature Reviews. Neurology·Dimitri M KullmannRobert C Wykes
Jul 2, 2014·Epilepsy Research and Treatment·Guglielmo LuccheseDarja Kanduc
Jul 29, 2015·Seizure : the Journal of the British Epilepsy Association·Michael P RassnerThomas M Freiman
Jan 21, 2014·Brain Structure & Function·Alex S FerecskóJohn G R Jefferys
Jul 18, 2020·Frontiers in Cellular Neuroscience·Gabriele LignaniVincenzo Marra
Jul 11, 2018·Nature Medicine·Andreas LiebDimitri M Kullmann
Dec 11, 2019·Journal of Clinical Medicine·Megumi AndohRyuta Koyama
Dec 29, 2020·Frontiers in Cellular Neuroscience·Eleonora VanniniVincenzo Marra
Mar 5, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jennifer C WongAndrew Escayg
Aug 22, 2021·Brain, Behavior, and Immunity·Gaia ScabiaUNKNOWN “Train the Brain” Consortium

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