Proconvulsant actions of intrahippocampal botulinum neurotoxin B in the rat

S. Bröer, D. Zolkowska, M. Gernert, Michael A Rogawski

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits.•Intrahippocampal BoNT/B caused delayed proconvulsant actions and seizures.•BoNT/B differs from other BoNTs that have been found to confer seizure protection.•The pro-epileptic actions of BoNT/B may be due to its ability to inhibit GABA release. Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target SNAP-25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000. unit) by convection-enhanced delivery caused a reduction in myoclonic twitch and clonic seizure thresholds in response to intravenous PTZ beginning about 6. days after the infusion. Handling-evoked and spontaneous convulsive seizures were observed in many BoNT/B-treated animals but not in vehicle-treated controls. Spontaneous electrographic seizure discharges were recorded in the dentate gyrus of animals that received local BoNT/B infusion. In addition, there was an increased frequency of interictal epileptiform spikes and sharp waves at the same recording site. BoNT/B-treated animals also exhibited tactile hyperresponsivity in comparison with vehicle-treated controls. This is the first demonstration that BoNT/B causes a delayed proconvulsant action when infused into the hippocampus. Local infusion of BoNT/B could be useful as a focal epilepsy model.

Original languageEnglish (US)
Pages (from-to)253-261
Number of pages9
JournalNeuroscience
Volume252
DOIs
StatePublished - Nov 12 2013

Fingerprint

Seizures
Neurotoxins
Pentylenetetrazole
Synapses
rimabotulinumtoxinB
Vesicle-Associated Membrane Protein 2
Convection
Partial Epilepsy
Dentate Gyrus
Brain
Touch
gamma-Aminobutyric Acid
Neurotransmitter Agents
Hippocampus

Keywords

  • Botulinum neurotoxin
  • Convection-enhanced delivery
  • Epilepsy
  • Hippocampus
  • Pentylenetetrazol
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Proconvulsant actions of intrahippocampal botulinum neurotoxin B in the rat. / Bröer, S.; Zolkowska, D.; Gernert, M.; Rogawski, Michael A.

In: Neuroscience, Vol. 252, 12.11.2013, p. 253-261.

Research output: Contribution to journalArticle

Bröer, S. ; Zolkowska, D. ; Gernert, M. ; Rogawski, Michael A. / Proconvulsant actions of intrahippocampal botulinum neurotoxin B in the rat. In: Neuroscience. 2013 ; Vol. 252. pp. 253-261.
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