Suppression of epileptogenesis by modification of N-methyl-D-aspartate receptor subunit composition.
The effects of altered N-methyl-D-aspartate (NMDA) receptor subunit composition on seizure development in kindling epilepsy were assessed in transgenic mice expressing high neuronal levels of NR2D under control of the calcium/calmodulin kinase II alpha subunit (alphaCaMKII) promoter. The NR2D subunit is normally present at very low levels in the mature forebrain. Transgenic 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 progressive lengthening of epileptiform activity, which normally occurs in kindling, was also dampened in transgenic animals. We conclude that NMDA receptor subunit composition determines the progression of experimental epilepsy.
Bengzon
J
J
Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden. jhan.bengzon@neurol.lu.se
Okabe
S
S
Lindvall
O
O
McKay
R D
RD
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D018076:DNA, Complementary; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017403:In Situ Hybridization; D007696:Kindling, Neurologic / Q000235:genetics; D007763:Lac Operon; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D016548:Prosencephalon / Q000737:chemistry / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000235:genetics*; D019076:Transgenes / Q000502:physiology
D018076:DNA, Complementary; C549071:Grin2d protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517671:Camk2a protein, mouse