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Volume 17, Number 21, Issue of November 1, 1997 pp. 8588-8595
Copyright ©1997 Society for Neuroscience

Status Epilepticus-Induced Alterations in Metabotropic Glutamate Receptor Expression in Young and Adult Rats

Received May 13, 1997; revised Aug. 18, 1997; accepted Aug. 20, 1997.

Eleonora M. Aronica, Jan A. Gorter, Marie-Christine Paupard, Sonja Y. Grooms, Michael V. L. Bennett, and R. Suzanne Zukin

Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461

In adult rats, kainic acid induces status epilepticus and delayed, selective cell loss of pyramidal neurons in the hippocampal CA3. In pup rats, kainate induces status epilepticus but not the accompanying neuronal cell death. The precise mechanisms underlying this age-dependent vulnerability to seizure-induced cell death are not understood. Metabotropic glutamate receptors (mGluRs) are developmentally and spatially regulated throughout the hippocampus and are implicated in seizure-induced damage. In the present study we used in situ hybridization to examine possible changes in mGluR expression at the level of the hippocampus after status epilepticus in postnatal day 10 (P10) pup and adult (P40) rats. Status epilepticus did not alter expression of mGluR1, mGluR3, or mGluR5 mRNAs. In pup and adult rats, status epilepticus induced a reduction in expression of mGluR2 mRNA in granule cells of the dentate gyrus. This change could lead to augmented glutamate release at mossy fiber synapses on CA3 pyramidal cells and thereby promote hyperexcitation. In pup but not adult rats, mGluR4 mRNA expression was enhanced in CA3 pyramidal neurons. Upregulation of presynaptic mGluR4 in pup CA3 neurons could lead to reduced transmitter release from CA3 axons, including recurrent collaterals, thereby reducing vulnerability of neonatal CA3 neurons to seizure-induced damage. These findings indicate that status epilepticus affects mGluR expression in a gene- and cell-specific manner, and that these changes vary with the developmental stage.

Key words: metabotropic glutamate receptors; receptor mRNAs; development; hippocampus; status epilepticus; seizures; epilepsy

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