Enhanced Epileptogenic Susceptibility in a Genetic Model of Reactive Synaptogenesis: The Spastic Han-Wistar RatCepeda C.a · Crawford C.A.b · Margulies J.E.c · Watson J.B.a · Levine M.S.a · Cohen R.W.d
aMental Retardation Research Center, University of California, Los Angeles; bDepartment of Psychology, California State University, San Bernardino; cDepartment of Surgery, Cedars-Sinai Medical Center, Los Angeles, and dDepartment of Biology, California State University, Northridge, Calif., USA
Our laboratory has been studying the spastic Han-Wistar (sHW) rat as a model of neuronal degeneration. Mutant sHW rats display a number of developmental abnormalities that eventually lead to hippocampal pyramidal cell death and synaptic reorganization starting around 30 days of age. The present study examined the contribution of hippocampal reorganization to the expression of seizures induced by systemic injections of kainic acid. Behavioral observations, EEG recordings and hippocampal Fos protein expression in these animals indicated that mutants develop paroxysmal discharges and seizures earlier than controls and the intensity of epileptic manifestations is greater. Kainate injections were lethal in 50% of mutants compared to only 5% of controls. Fos expression was increased approximately twofold in the mutant hippocampus, implicating abnormal excitation in this region. Additional studies in untreated animals indicated that GluR2 mRNA expression was significantly increased throughout the hippocampus in mutant animals, possibly contributing to the enhanced susceptibility to kainate treatment. These results confirm the role of synaptic reorganization in the increased propensity to develop epileptic discharges. Our data also underscore the usefulness of this natural model of cell degeneration and reactive synaptogenesis for understanding the mechanisms of neuronal hyperexcitability.
© 2002 S. Karger AG, Basel
Carlos Cepeda, PhD
Mental Retardation Research Center
760 Westwood Plaza, NPI 58-258, University of California Los Angeles
Los Angeles, CA 90095 (USA)
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Received: Received: April 29, 2002
Accepted: May 15, 2002
Number of Figures : 5, Number of Tables : 1, Number of References : 34
Vol. 24, No. 4, Year 2002 (Cover Date: July-August (Released December 2002))
Journal Editor: A.T. Campagnoni, Los Angeles, Calif.
ISSN: 0378–5866 (print), 1421–9859 (Online)
For additional information: http://www.karger.com/journals/dne