Glial glutamate transporters in animal models of epilepsy

• Main Author: Ingram, E.
• Published: University of Cambridge 2001
• Subjects: 615.1
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604933

The two glial transporters, GLAST (<SUB>L</SUB>-glutamate/L-aspartate transporter) and GLT-1 (<SUB>L</SUB>-glutamate transporter), are critical in regulating extracellular glutamate levels, being responsible for the majority of glutamate reuptake. The present study investigated GLAST and GLT-1 mRNA and protein levels in two animal models of inherited epilepsy: the EL (epileptic) mouse, a convulsive seizure model, and the GAERS (genetic absence epilepsy rat from Strasbourg) rat, a model of absence epilepsy. Additionally, tissue glutamate concentrations were determined in these animals by high pressure liquid chromatography (HPLC). Initially, polyclonal antibodies specific to mouse and rat GLT-1 and GLAST were generated and characterised. These antibodies revealed distribution patterns for the two transporters confirming those previously reported. <I>In situ</I> hybridisation and Western blot analysis revealed widespread reductions in GLT-1 mRNA in the brains of EL mice compared with control animals, accompanied by a decrease in GLT-1 protein in the parietal cortex, a region crucial to seizure initiation in this model. An increase in tissue glutamate concentration in the parietal cortex of EL mice was additionally observed. GLAST mRNA was also reduced in various brain regions of EL mice, with a reduction in protein observed in the hippocampus, a region essential for seizure generalisation. Glial glutamate transporter downregulation in these two regions may therefore play a role in seizure initiation and generalisation in the EL mouse. Similar analyses in GAERS rats revealed upregulation of GLT-1 and GLAST mRNA in thalamic and cortical regions, respectively, when compared with controls.