Brain Advance Access published online on November 25, 2005
Brain, doi:10.1093/brain/awh673
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1 Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Utrecht, The Netherlands
* To whom correspondence should be addressed. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors involved in the regulation of glutamatergic transmission. Recent studies indicate that excitatory group I mGluRs (mGluR1 and mGluR5) contribute to neurotoxicity and hyperexcitability during epileptogenesis. In this study, we examined the distribution of mGluR1
Received February 7, 2005
Revised August 30, 2005
Accepted September 30, 2005
Article
Up-regulation of hippocampal metabotropic glutamate receptor 5 in temporal lobe epilepsy patients
Robbert G. E. Notenboom 1 *,
David R. Hampson 2,
Gerard H. Jansen 3,
Peter C. van Rijen 4,
Cees W. M. van Veelen 4,
Onno van Nieuwenhuizen 5,
and
Pierre N. E. de Graan 1
2 Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada
3 Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands; Present address: Department of Pathology, The Ottawa Hospital, Ottawa, Ontario K1Y 4E9, Canada
4 Rudolf Magnus Institute of Neuroscience, Department of Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands
5 Rudolf Magnus Institute of Neuroscience, Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands
Robbert G. E. Notenboom, E-mail: r.g.e.notenboom{at}med.uu.nl
Abstract 
and mGluR5 immunoreactivity (IR) in hippocampal resection tissue from pharmaco-resistant temporal lobe epilepsy (TLE) patients. IR was detected with panels of receptor subtype specific antisera in hippocampi from TLE patients without (non-HS group) and with hippocampal sclerosis (HS group) and was compared with that of non-epileptic autopsy controls (control group). By immunohistochemistry and immunoblot analysis, we found a marked increase of mGluR5 IR in hippocampi from the non-HS compared with the control group. High mGluR5 IR was most prominent in the cell bodies and apical dendrites of hippocampal principal neurons and in the dentate gyrus molecular layer. In the HS group, this increase in neuronal mGluR5 IR was even more pronounced, but owing to neuronal loss the number of mGluR5-immunoreactive neurons was reduced compared with the non-HS group. IR for mGluR1 was found in the cell bodies of principal neurons in all hippocampal subfields and in stratum oriens and hilar interneurons. No difference in mGluR1 IR was observed between neurons in both TLE groups and the control group. However, owing to neuronal loss, the number of mGluR1-positive neurons was markedly reduced in the HS group. The up-regulation of mGluR5 in surviving neurons is probably a consequence rather than a cause of the epileptic seizures and may contribute to the hyperexcitability of the hippocampus in pharmaco-resistant TLE patients. Thus, our data point to a prominent role of mGluR5 in human TLE and indicate mGluR5 signalling as potential target for new anti-epileptic drugs.
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