ALTERED DISTRIBUTION OF THE ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONATE RECEPTOR SUBUNIT GLUR2(4) AND THE N-METHYL-D-ASPARTATE RECEPTOR SUBUNIT NMDAR1 IN THE HIPPOCAMPUS OF PATIENTS WITH TEMPORAL-LOBE EPILEPSY

In patients with therapy-refractory temporal lobe epilepsy (TLE), alte rations of glutamate receptors have been proposed as a mechanism for e nhanced excitability. Using commercially available monoclonal antibodi es specific for the N-methyl-D-aspartate (:NMDA) receptor subunit NMDA R1 and fur the alpha-amino-3-hydroxy-5-methyl-4-isosazole propionate r eceptor subunit GluR2(4). we have examined the distribution of these p olypeptides in human hippocampal tissue that was surgically removed fr om patients with intractable TLE. Surgical specimens were classified a ccording to the presence of Ammon's horn sclerosis (AHS) or a focal le sion in the temporal lobe. Cell counts and densitometric analysis of t he immunoreactivity patterns were carried out for all hippocampal subf ields. NMDAR1 and GluR2(4) levels were markedly reduced in patients wi th AHS, primarily in those subfields with focal lesions and in control specimens obtained at autopsy. In contrast, the molecular layer of th e dentate gyrus (DG-ML) showed significantly higher levels of GluR2(4) immunoreactivity in AHS compared to control tissue, while NMDAR1 show ed no significant up-regulation in this sublayer. When the receptor st aining intensity was normalized for alterations in neuronal density, n o significant alterations could be detected except for an increase in GluR2(4) in the DG-ML of patients with AHS. These changes may reflect synaptic reorganization observed in the DG-ML of specimens from patien ts with chronic intractable TLE.