Abstracts

The development of epilepsy, epileptogenesis, involves changes in gene expression. Pharmacological modulation of gene expression has been suggested as an approach to inhibit epileptogenesis. Levetiracetam (LEV) has antiepileptogenic properties, whereas phenytoin (PHT) does not. We hypothesized that regional alteration of gene expression after LEV treatment might point to brain regions that are important for epileptogenesis., Female Wistar rats were fed perorally with LEV (150 mg/kg) or PHT (75 mg/kg) twice daily for 90 days. N = 7 in each group. Affymetrix oligonucleotide-based microarrays were used to identify regional alterations in gene expression in pons/medulla oblongata, hippocampus and frontal cortex., LEV treatment caused changes in the expression of 65 genes in pons/medulla oblongata, 3 in hippocampus, and 1 in frontal cortex. PHT treatment, in contrast, caused changes in the expression of 3 genes in pons/medulla oblongata, 64 genes in hippocampus, and 322 genes in frontal cortex. Very little overlap between regions or drug treatments was observed with respect to affected genes. Median serum drug concentration 4-6 h after last dose was 231 [mu]mol LEV/L and 50 [mu]mol PHT/L., We conclude that antiepileptic drug treatment may cause dramatic and region-specific changes in mRNA levels, possibly reflecting their different action on receptors and ion channels in the plasma membrane. The finding that gene expression was altered predominantly in pons/medulla oblongata after LEV suggests that this brain region, which [italic]i.a.[/italic] harbours monoaminergic and cholinergic projection neurons, may be important for epileptogenesis.,