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

• Published in: The European journal of neuroscience 2000-07, Vol.12 (7), p.2333-2344
• Main Authors: Aronica, Eleonora, Van Vliet, Erwin A., Mayboroda, Oleg A., Troost, Dirk, Da Silva, Fernando H. Lopes, Gorter, Jan A.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Astrocytes - chemistry; Astrocytes - metabolism; Disease Models, Animal; Electroencephalography; Epilepsy, Temporal Lobe - metabolism; glia; Gliosis - metabolism; hippocampus; Male; metabotropic glutamate receptors; microglia; Rats; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate - analysis; Receptors, Metabotropic Glutamate - immunology; Receptors, Metabotropic Glutamate - metabolism; Status Epilepticus - metabolism; TGF-β; Transforming Growth Factor beta - analysis; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - metabolism; Up-Regulation - physiology; Vimentin - analysis
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.2000.00131.x

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)‐β 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‐β, 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‐β − may represent a novel mechanism for modulation of glial function and for changes in glial‐neuronal communication in the course of epileptogenesis.