Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.
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.
McDonald
J W
JW
Department of Neurology, University of Michigan, Ann Arbor.
Garofalo
E A
EA
Hood
T
T
Sackellares
J C
JC
Gilman
S
S
McKeever
P E
PE
Troncoso
J C
JC
Johnston
M V
MV
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
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