Expression and cell distribution of group I and group II metabotropic glutamate receptor subtypes in taylor-type focal cortical dysplasia.
OBJECTIVE
Focal cortical dysplasia (FCD) is known to be a major cause of intractable epilepsy. The cellular mechanism(s) underlying the epileptogenicity of FCD remain largely unknown. Because recent studies indicate that metabotropic glutamate receptor subtypes (mGluRs) play a role in epileptogenesis, we investigated the expression and cellular distribution pattern of mGluRs in FCD specimens.


METHODS
Immunocytochemical expression of group I and group II mGluR subtypes was investigated in 15 specimens of human FCD obtained during epilepsy surgery.


RESULTS
Strong mGluR1alpha and mGluR5 (group I mGluRs) immunoreactivity (IR) was observed in the majority of FCD specimens in dysplastic as well as in heterotopic neurons. mGluR1alpha was expressed in a subpopulation of neurons (mainly large dysplastic cells), whereas mGluR5 was represented in a higher percentage of dysplastic neuronal cells. Group II mGluRs (mGluR2/3) IR was observed less frequently than that in group I mGluRs and generally appeared in <10% of the dysplastic neurons. IR for all three mGluR subtypes was observed in balloon cells. mGluR2/3 appeared to be most frequently expressed in glial fibrillary acidic protein (GFAP)-positive balloon cells (glial type), and mGluR1alpha, in microtubule-associated protein (MAP)2-positive cells (neuronal type). mGluR5 was present in the majority of balloon cells. Occasionally glial mGluR1alpha IR was observed in bizarre glial cells with di- or multinuclei. Reactive astrocytes were intensively stained, mainly with mGluR5 and mGluR2/3.


CONCLUSIONS
The cellular distribution of mGluR subtypes, with high expression of mGluR1alpha and mGluR5 in dysplastic neurons, suggests a possible contribution of group I mGluRs to the intrinsic and high epileptogenicity of dysplastic cortical regions.
Aronica
Eleonora
E
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. e.aronica@amc.uva.nl
Gorter
Jan A
JA
Jansen
Gerard H
GH
van Veelen
Cees W M
CW
van Rijen
Peter C
PC
Ramkema
Marja
M
Troost
Dirk
D
D000293:Adolescent; D000328:Adult; D001253:Astrocytes / Q000473:pathology*; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D009421:Nervous System Malformations / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*
C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104077:metabotropic glutamate receptor type 1