ANALYSIS OF METABOTROPIC GLUTAMATE RECEPTOR SUBUNIT EXPRESSION IN MOUSE STRAINS WITH DIFFERENTIAL SUSCEPTIBILITY TO PILOCARPINE-INDUCED LIMBIC EPILEPSY
Abstract number :
1.103
Submission category :
Year :
2003
Submission ID :
3854
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Sergey V. Larionov, Jian Chen, Dirk Dietrich, Natalie Hoerold, Claudia Ullmann, Otmar D. Wiestler, Albert J. Becker Department of Neuropathology, University of Bonn Medical Center; Departments of Epileptology; Neurosurgery, University of Bonn Medical Cent
Human temporal lobe epilepsy is associated with altered distribution and expression of a variety of metabotropic glutamate receptors (mGluRs). Systemic administration of kainic acid or pilocarpine in various mouse strains has elicited significant differences in seizure susceptibility and hippocampal damage. Although the cellular mechanisms underlying these strain-dependent differences remain unclear, this variation appears to have a genetic background. Here, we have tested the hypothesis, that strain-dependent susceptibility to pilocarpine induced limbic epilepsy relates to distinct hippocampal expression patterns of mGluRs subunits.
We have studied the threshold to induce status epilepticus by systemic application of pilocarpine as well as the frequency and severity of recurrent seizures in the chronic epileptic stage of CD-1, C57Bl/6, and FVB/N mice (n=6 each). Using real time quantitative RT-PCR, expression of the mGluR1, 4, 5, and 7 subunits was determined in the hippocampal dentate gyrus granule cell layer (DG) (n=3 each) in the chronic epileptic stage.
FVB/N animals were significantly more sensitive to pilocarpine induced seizures compared to C57Bl/6 and CD-1 mice. After a latency period of several days, spontaneous tonic-clonic seizures could be observed in all animals. No significant differences were noted in the frequency of chronic recurrent seizures between the different strains. At the same time, the most severe chronic seizures developed in FVB/N mice. Real time RT-PCR analysis revealed an increased expression of mGluR4 in the DG of CD-1 (81.5% increase) and C57Bl/6 (67.2% increase) epileptic animals, whereas mGluR4 transcripts were decreased in the DG (18.0% decrease) of epileptic FVB/N mice. mGluR4 represents an inhibitory class III mGluRs associated with the reduction of intracellular cyclic AMP levels and calcium influx. Level of the mGluR1, 5, and 7 subunits remained unaltered under epileptic conditions.
Our results show an increase in the expression of inhibitory mGluR4 in DG cells of C57Bl/6 and CD-1 mice with an attenuated seizure phenotype vs. a decrease of mGluR4 in FVB/N mice with more severe pilocarpine-induced epilepsy. These findings raise the intriguing hypothesis that mGluRs contribute to the genetic basis of strain-dependent differences in susceptibility to experimental limbic epilepsy.
[Supported by: DFG (SFB TR3), BMBF (NGFN TP15), and BONFOR]