Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 28

In addition to receptor abnormalities, glutamate transporters, responsible for the removal of glutamate from the extracellular fluid, have been implicated in epilepsy (Meldrum et al., 1999). In situ hybridization studies have shown that the mRNA responsible for the rat glial glutamate transporter (GLT) is reduced in several brain regions in epilepsy-prone rats (Meldrum et al., 1999). GLT ‘knockout’ mice have been bred to provide homozygous mice, in which the GLT protein is not detected. In such mutant mice, glutamate uptake in cortical synaptosomes is 5.8% compared with the wild-type (Meldrum et al., 1999). The mutant mice show spontaneous seizures, with wild running and tonic extension, which is frequently fatal. In chronic seizure models (kindled seizures, spontaneous seizures and genetically epilepsy-prone rats), there are numerous reports of increases in extracellular glutamate during seizures (Meldrum et al., 1999). This strongly suggests that in these chronic models there are sustained functional alterations in mechanisms relating to the synaptic release of glutamate or its transport. GLT-1 astrocytic expression was reduced in four Shetland sheepdogs with IE (Morita et al., 2005). In these dogs it was suggested that decreased expression of the transporter might be related to development of status epilepticus.

There is not as yet any genetically determined epilepsy syndrome occurring spontaneously in man or mouse that can be ascribed to a primary gene defect involving a glutamate receptor or transporter.