Abstracts

RATIONALE: We have compared the expression of genes at cortical epileptic foci with the expression of the same genes at non-spiking regions of the same cortex taken at epilepsy surgery as a means of identifying genes that promote or maintain the epileptic state of that tissue.
METHODS: We have used microarray analysis to screen for genes that are abnormally expressed at human epileptic foci in cortex mapped using subdural grid recording electrodes. Genes identified, were confirmed by RT-PCR and localized in adjacent cortical regions by in situ hybridization.
RESULTS: Microarray analysis revealed genes with both increased and decreased expression levels at the focus. One of these genes identified to be reduced at the epileptic focus was the Glutamate Transporter-1 gene (GLT-1). Adjacent brain tissue from the same epileptic focus analyzed by in situ hybridization revealed that GLT-1 mRNA was expressed in neurons. RT-PCR demonstrated similar reductions in GLT-1 mRNA levels in cortical epileptic foci of some, but not all patients examined.
CONCLUSIONS: This study lays the groundwork for the development of methods to map gene expression patterns as a function of electrical excitability in human cortex and raises the exciting possibility that the hyperexcitability of epileptic cortex may arise in part from a failure in the reuptake of glutamate through reduced GLT-1 expression in neurons. Consistently, a recent report has found that mice deficient in this gene have lethal spontaneous seizures.
Support: This work was funded by a Junior Investigaor Award from the Epilepsy Foundation (JAL) and a Ralph Wilson Biomedical Scholar Award (JAL).