Increased Tyrosine Phosphorylation of the NMDA Receptor Subunit NR2A/B in Human Epileptogenic Cortex Associated with Cortical Dysplasia
Abstract number :
2.047
Submission category :
Year :
2001
Submission ID :
2951
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
Z. Ying, MD PHD, Neurology, The Cleveland Clinic, Cleveland, OH; I. Najm, MD, Neurology, The Cleveland Clinic, Cleveland, OH; W. Bingaman, MD, Neurosurgery, The Cleveland Clinic, Cleveland, OH; E. Hadar, MD, Neurology, The Cleveland Clinic, Cleveland, OH;
RATIONALE: The NMDA receptor is a principal subtype of ionotropic excitatory amino acid receptor and has been implicated in the expression of epileptogenicity in human focal cortical dysplasias: Electrophysiologically-verified human cortical samples showed a differential increase of NMDAR2 (NR2A/B) subunit protein and its co-assembly with NR1 subunits. The function of NMDA receptor is regulated by protein phosphorylation at tyrosine residues. Recently, tyrosine phosphorylation of NMDA receptor has been shown to increase glutamate-activated currents and induce long-term potentiation. We hypothesized that the levels of tyrosine phosphorylation of NR2A/B would be increased in human epileptogenic cortex.
METHODS: We used co-immunoprecipitation with anti-NR2A/B antibody and immunoblotting with anti-phosphotyrosine antibody to quantify the levels of tyrosine phosphorylation of NR2A/B in the membrane proteins of brain tissues from three patients suffering from medically intractable neocortical epilepsy associated with cortical dysplasia. Based on direct electrocorticographic subdural grid recordings, resected cortical tissues were grouped into epileptogenic and non-epileptogenic.
RESULTS: In all 3 patients the amounts of immunoprecipitated complexes, which reflect the levels tyrosine phosphorylation of NR2A/B were increased in epileptogenic as compared to non-epileptogenic neocortical areas.
CONCLUSIONS: These results suggest that increased tyrosine phosphorylation of NR2B/B at neuronal membrane is a cellular mechanism that may contribute to putative increased hyperexcitability and epileptogenicity in human focal cortical dysplasia.