Ionotropic and metabotropic glutamate receptor protein expression in glioneuronal tumours from patients with intractable epilepsy

Glioneuronal tumours are an increasingly recognized cause of chronic pharma co-resistant epilepsy. In the present study the immunocytochemical expressi on of various glutamate receptor (GluR) subtypes was investigated in 41 gan gliogliomas (GG) and 16 dysembryoplastic neuroepithelial tumours (DNT) from patients with intractable epilepsy. Immunocytochemistry with antibodies sp ecific for ionotropic NR1, NR2A/B (NMDA) GluR1, GluR2 (AMPA), GluR5-7 (kain ate), and metabotropic mGluR1, mGluR2-3, mGluR5, mGluR7a subtypes demonstra ted in both GG and DNT the presence of an highly differentiated neuronal po pulation, containing subunits from each receptor class. More than 50% of tu mours 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 (m GluR1 and mGluR5) were highly represented in the neuronal component of the tumours. Immunolabelling for several GluRs was also present in the glial co mponent. 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 transmis sion in the mechanisms underlying the intrinsic and high epileptogenicity o f these lesions.