Selective coexpression of NMDAR2A/B and NMDAR1 subunit proteins in dysplastic neurons of human epileptic cortex

NR1 and NR2 are the two gene families for the NMDA receptor, In vitro studi es show that while NR2 alone is nonfunctional, NR1 alone produces weak curr ents to glutamate or NMDA. We previously showed by immunocytochemistry (ICC ) that in normal appearing, nonepileptic human cortical neurons, only NR1 a nd not NR2 proteins were expressed, in contrast to the presence of both NR1 and NR2 in normal rat cortical neurons. We also showed, in dysplastic epil eptic cortex, that both NR1 and NR2 were highly expressed using ICC on adja cent 30-mu m sections. However, the relative coexpressions of NR1 and NR2 p roteins in single neurons in single sections of human epileptic cortex were unknown, In this study, we used double-labeled immunofluorescence and conf ocal microscopy to examine the distribution and coexpression of subunit pro teins for NR1 and NR2A/B in both nondysplastic (control comparison) and dys plastic regions of human brain resected for the treatment of intractable ep ilepsy (11 patients), In nondysplastic regions, cortical neurons did not ha ve immunoreactivity (ir) for NR2A/B, whereas NR1-ir was abundant. By contra st, dysplastic neurons in the regions with epileptic cortical dysplasia sho wed intense NR2A/B-ir in the somata and their dendritic processes. These sa me NR2A/B-ir dysplastic neurons were colabeled by NR1, These results demons trate directly that dysplastic neurons express both NR2A/B and NR1 proteins , whereas nondysplastic cortical neurons express only NR1 proteins. Selecti ve coexpression of NR2A/B and NR1 in dysplastic neurons suggests that NR2A/ B may form heteromeric NR1-NR2 coassemblies and hyperexcitability in dyspla stic neurons that could contribute to focal seizure onset. (C) 1999 Academi c Press.