Antiepileptic effects of botulinum neurotoxin E

Laura Costantin, Yuri Bozzi, Cristina Richichi, Alessandro Viegi, Flavia Antonucci, Marcella Funicello, Marco Gobbi, Tiziana Mennini, Ornella Rossetto, Cesare Montecucco, Lamberto Maffei, Annamaria Vezzani, Matteo Caleo

Research output: Contribution to journalArticle

Abstract

Experimental studies suggest that the delivery of antiepileptic agents into the seizure focus might be of potential utility for the treatment of focal-onset epilepsies. Botulinum neurotoxin E (BoNT/E) causes a prolonged inhibition of neurotransmitter release after its specific cleavage of the synaptic protein synaptosomal-associated protein of 25 kDa (SNAP-25). Here, we show that BoNT/E injected into the rat hippocampus inhibits glutamate release and blocks spike activity of pyramidal neurons. BoNT/E effects persist for at least 3 weeks, as determined by immunodetection of cleaved SNAP-25 and loss of intact SNAP-25. The delivery of BoNT/E to the rat hippocampus dramatically reduces both focal and generalized kainic acid-induced seizures as documented by behavioral and electrographic analysis. BoNT/E treatment also prevents neuronal loss and long-term cognitive deficits associated with kainic acid seizures. Moreover, BoNT/E-injected rats require 50% more electrical stimulations to reach stage 5 of kindling, thus indicating a delayed epileptogenesis. We conclude that BoNT/E delivery to the hippocampus is both antiictal and antiepileptogenic in experimental models of epilepsy.

Original languageEnglish
Pages (from-to)1943-1951
Number of pages9
JournalJournal of Neuroscience
Volume25
Issue number8
DOIs
Publication statusPublished - Feb 23 2005

Fingerprint

Anticonvulsants
Synaptosomal-Associated Protein 25
Hippocampus
Seizures
Kainic Acid
Partial Epilepsy
Pyramidal Cells
botulinum toxin type E
Electric Stimulation
Neurotransmitter Agents
Glutamic Acid
Epilepsy
Theoretical Models
Proteins

Keywords

  • Hippocampal kindling
  • Kainic acid
  • Morris water maze
  • Neuronal death
  • Neurotransmitter release
  • Seizures

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Costantin, L., Bozzi, Y., Richichi, C., Viegi, A., Antonucci, F., Funicello, M., ... Caleo, M. (2005). Antiepileptic effects of botulinum neurotoxin E. Journal of Neuroscience, 25(8), 1943-1951. https://doi.org/10.1523/JNEUROSCI.4402-04.2005

Antiepileptic effects of botulinum neurotoxin E. / Costantin, Laura; Bozzi, Yuri; Richichi, Cristina; Viegi, Alessandro; Antonucci, Flavia; Funicello, Marcella; Gobbi, Marco; Mennini, Tiziana; Rossetto, Ornella; Montecucco, Cesare; Maffei, Lamberto; Vezzani, Annamaria; Caleo, Matteo.

In: Journal of Neuroscience, Vol. 25, No. 8, 23.02.2005, p. 1943-1951.

Research output: Contribution to journalArticle

Costantin, L, Bozzi, Y, Richichi, C, Viegi, A, Antonucci, F, Funicello, M, Gobbi, M, Mennini, T, Rossetto, O, Montecucco, C, Maffei, L, Vezzani, A & Caleo, M 2005, 'Antiepileptic effects of botulinum neurotoxin E', Journal of Neuroscience, vol. 25, no. 8, pp. 1943-1951. https://doi.org/10.1523/JNEUROSCI.4402-04.2005
Costantin L, Bozzi Y, Richichi C, Viegi A, Antonucci F, Funicello M et al. Antiepileptic effects of botulinum neurotoxin E. Journal of Neuroscience. 2005 Feb 23;25(8):1943-1951. https://doi.org/10.1523/JNEUROSCI.4402-04.2005
Costantin, Laura ; Bozzi, Yuri ; Richichi, Cristina ; Viegi, Alessandro ; Antonucci, Flavia ; Funicello, Marcella ; Gobbi, Marco ; Mennini, Tiziana ; Rossetto, Ornella ; Montecucco, Cesare ; Maffei, Lamberto ; Vezzani, Annamaria ; Caleo, Matteo. / Antiepileptic effects of botulinum neurotoxin E. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 8. pp. 1943-1951.
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