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

Eur J Neurosci. 2000 Jul;12(7):2333-44. 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)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Astrocytes / chemistry
  • Astrocytes / metabolism*
  • Disease Models, Animal
  • Electroencephalography
  • Epilepsy, Temporal Lobe / metabolism*
  • Gliosis / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / analysis
  • Receptors, Metabotropic Glutamate / immunology
  • Receptors, Metabotropic Glutamate / metabolism*
  • Status Epilepticus / metabolism
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation / physiology*
  • Vimentin / analysis


  • Antibodies
  • Grm5 protein, rat
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Transforming Growth Factor beta
  • Vimentin
  • metabotropic glutamate receptor 3