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 studies show that while NR2 alone is nonfunctional, NR1 alone produces weak currents to glutamate or NMDA. We previously showed by immunocytochemistry (ICC) that in normal appearing, nonepileptic human cortical neurons, only NR1 and 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 epileptic cortex, that both NR1 and NR2 were highly expressed using ICC on adjacent 30-microm sections. However, the relative coexpressions of NR1 and NR2 proteins in single neurons in single sections of human epileptic cortex were unknown. In this study, we used double-labeled immunofluorescence and confocal microscopy to examine the distribution and coexpression of subunit proteins for NR1 and NR2A/B in both nondysplastic (control comparison) and dysplastic regions of human brain resected for the treatment of intractable epilepsy (11 patients). In nondysplastic regions, cortical neurons did not have immunoreactivity (ir) for NR2A/B, whereas NR1-ir was abundant. By contrast, dysplastic neurons in the regions with epileptic cortical dysplasia showed intense NR2A/B-ir in the somata and their dendritic processes. These same NR2A/B-ir dysplastic neurons were colabeled by NR1. These results demonstrate directly that dysplastic neurons express both NR2A/B and NR1 proteins, whereas nondysplastic cortical neurons express only NR1 proteins. Selective coexpression of NR2A/B and NR1 in dysplastic neurons suggests that NR2A/B may form heteromeric NR1-NR2 coassemblies and hyperexcitability in dysplastic neurons that could contribute to focal seizure onset.
Ying
Z
Z
Department of Neurosciences, Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA. yingz@ccf.org
Babb
T L
TL
Mikuni
N
N
Najm
I
I
Drazba
J
J
Bingaman
W
W
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D017034:Epilepsy, Frontal Lobe / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D005810:Multigene Family; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000235:genetics*
D016194:Receptors, N-Methyl-D-Aspartate