NMDA receptor alterations in neurons from pediatric cortical dysplasia tissue.
The subunit composition of glutamate receptors affects their functional properties, and could contribute to abnormal electrophysiology in pediatric cortical dysplasia (CD). We examined electrophysiological responses and subunit assembly of N-methyl-D-aspartate (NMDA) receptors in acutely dissociated normal-appearing pyramidal and cytomegalic neurons from CD tissue and normal-appearing pyramidal neurons from non-CD tissue. In most cytomegalic and approximately 30% of normal-appearing pyramidal neurons from CD tissue, NMDA currents showed decreased Mg(2+) sensitivity compared with neurons from non-CD tissue. Ifenprodil had less effect in CD compared with non-CD neurons, indicating a functional loss of NR2B subunits. NMDA-evoked current density was decreased in cytomegalic compared with normal-appearing neurons. Single-cell reverse transcriptase polymerase chain reaction showed that all non-CD neurons expressed NR2B subunit mRNA. By comparison, 22% of pyramidal neurons in CD tissue lacked NR2B mRNA. Immunofluorescence showed a decrease in NR2B subunit expression in cytomegalic neurons and a subset of normal-appearing pyramidal neurons from CD tissue. Taken together, these results demonstrate the presence of NMDA receptors with altered subunit composition and Mg(2+) sensitivity that could contribute to functional abnormalities in CD.
André
Véronique M
VM
Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Flores-Hernández
Jorge
J
Cepeda
Carlos
C
Starling
Amaal J
AJ
Nguyen
Snow
S
Lobo
Mary Kay
MK
Vinters
Harry V
HV
Levine
Michael S
MS
Mathern
Gary W
GW
D000293:Adolescent; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000187:drug effects / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D008274:Magnesium; C010739:ifenprodil