vGLUT2 heterozygous mice show more susceptibility to clonic seizures induced by pentylenetetrazol.
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.
Schallier
Anneleen
A
Department of Pharmaceutical Chemistry, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
Massie
Ann
A
Loyens
Ellen
E
Moechars
Diederik
D
Drinkenburg
Wilhelmus
W
Michotte
Yvette
Y
Smolders
Ilse
I
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*
D003292:Convulsants; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D010433:Pentylenetetrazole