title: NMDA receptor alterations in neurons from pediatric cortical dysplasia tissue.
abstract: 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.
authors.affiliation: Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Véronique M
authors.initials: VM
authors.lastname: André
authors.forename: Jorge
authors.initials: J
authors.lastname: Flores-Hernández
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.forename: Amaal J
authors.initials: AJ
authors.lastname: Starling
authors.forename: Snow
authors.initials: S
authors.lastname: Nguyen
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Lobo
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Michael S
authors.initials: MS
authors.lastname: Levine
authors.forename: Gary W
authors.initials: GW
authors.lastname: Mathern
mesh_terms: 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
chemical_list: D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D008274:Magnesium; C010739:ifenprodil