title: Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.
abstract: We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor.
authors.forename: J W
authors.initials: JW
authors.lastname: McDonald
authors.forename: E A
authors.initials: EA
authors.lastname: Garofalo
authors.forename: T
authors.initials: T
authors.lastname: Hood
authors.forename: J C
authors.initials: JC
authors.lastname: Sackellares
authors.forename: S
authors.initials: S
authors.lastname: Gilman
authors.forename: P E
authors.initials: PE
authors.lastname: McKeever
authors.forename: J C
authors.initials: JC
authors.lastname: Troncoso
authors.forename: M V
authors.initials: MV
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D005260:Female; D005998:Glycine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017478:Receptors, Phencyclidine
chemical_list: D000596:Amino Acids; D010069:Oxadiazoles; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D010622:Phencyclidine; D005998:Glycine