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.

Expression of human epileptic temporal lobe neurotransmitter receptors inXenopusoocytes: An innovative approach to study epilepsy

“…Evidence from animal models, and from human studies, suggests that altered expression of ionotropic GABA A and GluRs may contribute to the pathophysiology of TLE (2,29). To study in more detail the neurotransmitter receptors of the epileptic brain, we decided to see whether it was possible to transfer the receptors from human brain tissue, surgically resected from intractable TLE patients, into the membrane of Xenopus oocytes.…”

GABA and Epileptogenesis

“…In tissue resected from patients with temporal lobe epilepsy (TLE), the number of GABA, receptors is reduced in areas of hippocampus showing neuronal cell loss (59)(60)(61). Reduced BZD binding to GABA, receptors in mesial temporal lobe of such patients can be detected in vivo by noninvasive positron emission tomography imaging (62,63).…”

Rundown of GABA type A receptors is a dysfunction associated with human drug-resistant mesial temporal lobe epilepsy

“…In the last years, intractable TLE has been studied through the analyses of surgically resected TL and mesial structures by using molecular and electrophysiological approaches. This has led to the discovery of alterations of excitatory and inhibitory amino acid receptor binding and of their transporter systems (1)(2)(3)(4), altered expression of neurotransmitter receptors (5-7) and of GABA inhibitory function (8)(9)(10)(11), and overexpression of BDNF (12). Interestingly, GABA type A receptors (GABA A -receptors) originating from the TLE temporal neocortex exhibit a surprisingly low apparent affinity for GABA and a marked current elicited by GABA (GABA A -current) rundown upon repetitive stimulation with GABA.…”