Ionotropic and metabotropic glutamate receptor protein expression in glioneuronal tumours from patients with intractable epilepsy.
Glioneuronal tumours are an increasingly recognized cause of chronic pharmaco-resistant epilepsy. In the present study the immunocytochemical expression of various glutamate receptor (GluR) subtypes was investigated in 41 gangliogliomas (GG) and 16 dysembryoplastic neuroepithelial tumours (DNT) from patients with intractable epilepsy. Immunocytochemistry with antibodies specific for ionotropic NR1, NR2A/B (NMDA) GluR1, GluR2 (AMPA), GluR5-7 (kainate), and metabotropic mGluR1, mGluR2-3, mGluR5, mGluR7a subtypes demonstrated in both GG and DNT the presence of an highly differentiated neuronal population, containing subunits from each receptor class. More than 50% of tumours contained a high percentage of neuronal cells immunolabelled for NMDA, AMPA and kainate receptor subunits. A high percentage of neurones showed strong expression of NR2A-B, which co-localized with NR1. Group I mGluRs (mGluR1 and mGluR5) were highly represented in the neuronal component of the tumours. Immunolabelling for several GluRs was also present in the glial component. Increased expression of mGluR2-3, mGluR5 and GluR5-7 was observed in reactive astrocytes in the perilesional zone compared to normal cortex. The neurochemical profile of glioneuronal tumours, with high expression of specific GluR subtypes, supports the central role of glutamatergic transmission in the mechanisms underlying the intrinsic and high epileptogenicity of these lesions.
Aronica
E
E
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. e.aronica@amc.uva.nl
Yankaya
B
B
Jansen
G H
GH
Leenstra
S
S
van Veelen
C W
CW
Gorter
J A
JA
Troost
D
D
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D002648:Child; D004827:Epilepsy / Q000150:complications*; D005260:Female; D018303:Ganglioglioma / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018302:Neoplasms, Neuroepithelial / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D017470:Receptors, Glutamate / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013724:Teratoma / Q000150:complications* / Q000473:pathology
D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate