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 rec eptor 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 neuron s showing staining in both the cell bodies and dendritic profiles. How ever, 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 cont rast, the antibody to splice variants of NR1-1a, -1b, 2a, -2b, -3a, -3 b, -4a, and -4b labeled both dysplastic and nondysplastic neurons. The different labeling patterns by these two antibodies indicate that var iants of NMDAR1-3a, -3b, -4a, and -4b are present in nondysplastic neu rons. Both dysplastic neurons and nondysplastic neurons were immunorea ctive to AMPA GluR2/3, but denser immunoreactivity was observed in dys plastic neurons. We also found that the locations of dysplastic neuron s labeled by NMDAR2A/B were related to focal epileptic EEG seizure ons ets or spiking and to focal behavioral seizure types. Our results sugg est that there is hyperexcitability of dysplastic cortical regions, at least in part, from the presence of NMDAR2 subunits and selectively e xpressed NMDAR1 splice variants in dysplastic neurons.