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Proconvulsant actions of intrahippocampal botulinum neurotoxin B in the rat
- Source :
- Neuroscience. 252:253-261
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- 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 1,000 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.
- Subjects :
- Male
Botulinum Toxins
hippocampus
polyaryletheretherketone
Hippocampus
Convulsants
vesicle-associated membrane protein 2
Neurodegenerative
Pharmacology
Type A
Rats, Sprague-Dawley
chemistry.chemical_compound
Epilepsy
Psychology
EEG
Botulinum Toxins, Type A
Neurotransmitter
CED
ANOVA
General Neuroscience
botulinum neurotoxin
Electroencephalography
pentylenetetrazol
Foodborne Illness
Infectious Diseases
VAMP2
synaptosomal-associated protein of 25 kDa
Neurological
Excitatory postsynaptic potential
Cognitive Sciences
medicine.drug
analysis of variance
Intraventricular
seizure
unit
PTZ
Convection
Inhibitory postsynaptic potential
BoNT
Article
Injections
PEEK
Seizures
medicine
Animals
Ictal
Pentylenetetrazol
Injections, Intraventricular
Neurology & Neurosurgery
convection-enhanced delivery
Animal
business.industry
Dentate gyrus
Neurosciences
electroencephalogram
medicine.disease
Rats
Brain Disorders
Disease Models, Animal
chemistry
Disease Models
SNAP-25
Pentylenetetrazole
Sprague-Dawley
business
Neuroscience
Subjects
Details
- ISSN :
- 03064522
- Volume :
- 252
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....85ca6e4b908783ec86b58ec3c8843b75