Suppression of epileptogenesis by modification of N-methyl-D-aspartate receptor subunit composition

The effects of altered N-methyl-D-aspartate (NMDA) receptor subunit composi tion on seizure development in kindling epilepsy were assessed in transgeni c mice expressing high neuronal levels of NR2D under control of the calcium /calmodulin kinase II alpha subunit (alpha CaMKII) promoter. The NR2D subun it is normally present at very low levels in the mature forebrain. Transgen ic mice showed a marked reduction of amygdala kindling development. Spread of epileptic activity was retarded and generalized seizures appeared later in animals overexpressing NR2D compared with wild-type mice. The progressiv e lengthening of epileptiform activity, which normally occurs in kindling, was also dampened in transgenic animals. We conclude that NMDA receptor sub unit composition determines the progression of experimental epilepsy.