Quantitative autoradiographic analysis of ionotropic glutamate receptor subtypes in human temporal lobe epilepsy: up-regulation in reorganized epileptogenic hippocampus.

Abstract

Medically intractable temporal lobe epilepsy is a common disease typically associated with hippocampal damage (sclerosis) and synaptic remodelling. These changes could include increased glutamate receptor expression, enhancing excitability and the potential for neuronal injury. We directly assessed this hypothesis using quantitative in vitro receptor autoradiography to determine the densities of glutamate-, NMDA-, quisqualate/alpha-amino-3-hydroxy-5-methyl-isoxazoleproprionic acid (AMPA)- and kainic acid-preferring binding sites in surgically removed hippocampi from patients with mesial temporal lobe epilepsy (sclerosis; MTLE) and patients with mass-associated temporal lobe epilepsy (no sclerosis; MaTLE), compared with autopsy material. Neuronal cell counts and in situ total protein densities were also obtained. In general, MaTLE and autopsy binding densities were indistinguishable. In contrast, some regions of MTLE hippocampi exhibited decreased receptor densities, with a corresponding loss of protein. In the hilus and CA1, however, ligand binding densities did not differ from the comparison groups in spite of markedly reduced protein content, consistent with increased glutamate receptor density. Kainate-preferring sites were distributed differently from the other glutamate subtypes and were uniformly decreased throughout the MTLE hippocampus, except for a unique expression within the outer dentate molecular layer. Along with increased NMDA and AMPA receptor densities in the hilus and CA1, this distinctive population of kainate receptors establishes that increased glutamate receptor expression is a feature of the remodelled MTLE hippocampus. These observations suggest that enhanced sensitivity to glutamate may be an important element in the pathophysiology of temporal lobe epilepsy.

• Authors: M L Brines, S Sundaresan, D D Spencer, N C de Lanerolle
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 9 Issue 10 Pg. 2035-44 (Oct 1997) ISSN: 0953-816X [Print] France
• PMID: 9421164 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, AMPA
• Receptors, Glutamate
• Receptors, N-Methyl-D-Aspartate
• Tritium
• Glutamic Acid

Topics

• Adult
• Aged
• Autopsy
• Autoradiography (methods)
• Epilepsy, Temporal Lobe (metabolism, pathology)
• Female
• Glutamic Acid (metabolism)
• Hippocampus (metabolism, pathology)
• Humans
• Male
• Middle Aged
• Neurons (metabolism, pathology)
• Receptors, AMPA (analysis, biosynthesis)
• Receptors, Glutamate (analysis, biosynthesis)
• Receptors, N-Methyl-D-Aspartate (analysis, biosynthesis)
• Reference Values
• Tritium
• Up-Regulation