title: vGLUT2 heterozygous mice show more susceptibility to clonic seizures induced by pentylenetetrazol.
abstract: Glutamate, the most abundant excitatory neurotransmitter in the central nervous system, is well known to be implicated in epileptic seizures. Therefore, impairments in glutamate transport could have an involvement in the mechanism of epileptogenesis. The uptake of glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (vGLUTs). There are three known vGLUT isoforms, vGLUT1-3. In this study, we are particularly interested in the vGLUT2 isoform. We investigated the possible role of vGLUT2 in pentylenetetrazol (PTZ)-induced seizure generation. Seizure threshold of PTZ was compared in vGLUT2 heterozygous knock out (HET) and wild type (WT) mice. In comparison with their WT littermates a lower dose of PTZ was needed in the vGLUT2 HET mice until the onset of the first myoclonic jerk. The threshold for PTZ-induced clonic seizure activity was also lower in the vGLUT2 HET mice. These results indicate, for the first time, that vGLUT2 is likely involved in the epileptogenesis of generalized seizures.
authors.affiliation: Department of Pharmaceutical Chemistry, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Schallier
authors.forename: Ann
authors.initials: A
authors.lastname: Massie
authors.forename: Ellen
authors.initials: E
authors.lastname: Loyens
authors.forename: Diederik
authors.initials: D
authors.lastname: Moechars
authors.forename: Wilhelmus
authors.initials: W
authors.lastname: Drinkenburg
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D003292:Convulsants; D004569:Electroencephalography; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000235:genetics; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced* / Q000235:genetics*; D006579:Heterozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics*; D013686:Telemetry; D013788:Thalamus / Q000187:drug effects / Q000502:physiology; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics*
chemical_list: D003292:Convulsants; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D010433:Pentylenetetrazole