title: Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy.
abstract: Reactive gliosis is a prominent morphological feature of mesial temporal lobe epilepsy. Because astrocytes express glutamate receptors, we examined changes in metabotropic glutamate receptor (mGluR) 2/3, mGluR5 and transforming growth factor (TGF)-beta in glial cells of the hippocampal regions in an experimental rat model of spontaneous seizures. Rats that exhibited behavioural status epilepticus (SE) directly after 1 h of electrical angular bundle stimulation, displayed chronic spontaneous seizures after a latent period of 1-2 weeks as observed using continuous electrographic monitoring. SE resulted in hypertrophy of astrocytes and microglia activation throughout the hippocampus as revealed by immunolabelling studies. A dramatic, seizure intensity-dependent increase in vimentin immunoreactivity (a marker for reactive astrocytes) was revealed in CA3 and hilar regions where prominent neuronal loss occurs. Increased vimentin labelling was first apparent 24 h after onset of SE and persisted up to 3 months. mGluR2/3 and mGluR5 protein expression increased markedly in glial cells of CA3 and hilus by 1 week after SE, and persisted up to 3 months after SE. Double immunolabelling of brain sections with vimentin confirmed co-localization with glial fibrillary acidic protein (GFAP), mGluR2/3 and mGluR5 in reactive astrocytes. TGF-beta, a cytokine implicated in mGluR3-mediated neuroprotection, was also upregulated during the first 3 weeks after SE throughout the hippocampus. This study demonstrates seizure-induced upregulation of two mGluR subtypes in reactive astrocytes, which - together with the increased production of TGF-beta - may represent a novel mechanism for modulation of glial function and for changes in glial-neuronal communication in the course of epileptogenesis.
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Aronica
authors.forename: E A
authors.initials: EA
authors.lastname: van Vliet
authors.forename: O A
authors.initials: OA
authors.lastname: Mayboroda
authors.forename: D
authors.initials: D
authors.lastname: Troost
authors.forename: F H
authors.initials: FH
authors.lastname: da Silva
authors.forename: J A
authors.initials: JA
authors.lastname: Gorter
mesh_terms: D000818:Animals; D000906:Antibodies; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D014746:Vimentin / Q000032:analysis
chemical_list: D000906:Antibodies; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016212:Transforming Growth Factor beta; D014746:Vimentin; C102718:metabotropic glutamate receptor 3