Induced expression of NMDAR2 proteins and differential expression of NMDAR1 splice variants in dysplastic neurons of human epileptic neocortex.
Immunocytochemistry was used to study the expressions of glutamate receptor subunit proteins for NMDAR2A/B, NMDAR1 splice variants, and AMPA Glu-R2/3 in human brain resected for intractable epilepsy associated with cortical dysplasia. NMDAR2A/B intensely labeled dysplastic neurons showing staining in both the cell bodies and dendritic profiles. However, nondysplastic neurons were not immunoreactive to NMDAR2A/B. The antibody selective to NMDAR1 splice variants of NR1-1a. -1b, -2a, and -2b labeled dysplastic neurons, but few nondysplastic neurons. In contrast, the antibody to splice variants of NR1-1a, -1b, 2a, -2b, -3a, -3b, -4a, and -4b labeled both dysplastic and nondysplastic neurons. The different labeling patterns by these two antibodies indicate that variants of NMDAR1-3a, -3b, -4a, and -4b are present in nondysplastic neurons. Both dysplastic neurons and nondysplastic neurons were immunoreactive to AMPA GluR2/3, but denser immunoreactivity was observed in dysplastic neurons. We also found that the locations of dysplastic neurons labeled by NMDAR2A/B were related to focal epileptic EEG seizure onsets or spiking and to focal behavioral seizure types. Our results suggest that there is hyperexcitability of dysplastic cortical regions, at least in part, from the presence of NMDAR2 subunits and selectively expressed NMDAR1 splice variants in dysplastic neurons.
Ying
Z
Z
Department of Neuroscience, The Cleveland Clinic Foundation, OH 44195, USA.
Babb
T L
TL
Comair
Y G
YG
Bingaman
W
W
Bushey
M
M
Touhalisky
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D018091:Receptors, AMPA / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2