Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy

Reactive gliosis is a prominent morphological feature of mesial temporal lo be epilepsy. Because astrocytes express glutamate receptors, we examined ch anges in metabotropic glutamate receptor (mGluR) 2/3, mGluR5 and transformi ng growth factor (TGF)-beta in glial cells of the hippocampal regions in an experimental rat model of spontaneous seizures. Rats that exhibited behavi oural status epilepticus (SE) directly after 1 h of electrical angular bund le stimulation, displayed chronic spontaneous seizures after a latent perio d of 1-2 weeks as observed using continuous electrographic monitoring. SE r esulted in hypertrophy of astrocytes and microglia activation throughout th e hippocampus as revealed by immunolabelling studies. A dramatic, seizure i ntensity-dependent increase in vimentin immunoreactivity (a marker for reac tive astrocytes) was revealed in CA3 and hilar regions where prominent neur onal loss occurs. Increased vimentin labelling was first apparent 24 h afte r onset of SE and persisted up to 3 months. mGluR2/3 and mGluR5 protein exp ression 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 acid ic protein (GFAP), mGluR2/3 and mGluR5 in reactive astrocytes. TGF-beta, a cytokine implicated in mGluR3-mediated neuroprotection, was also upregulate d 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 - m ay represent a novel mechanism for modulation of glial function and for cha nges in glial-neuronal communication in the course of epileptogenesis.