Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis

H. Potschka, E. Krupp, U. Ebert, C. Gümbel, C. Leichtlein, B. Lorch, A. Pickert, S. Kramps, K. Young, U. Grüne, A. Keller, M. Welschof, G. Vogt, B. Xiao, P. F. Worley, Wolfgang Löscher, Holger Hiemisch

Research output: Contribution to journalArticle

Abstract

Despite an extensive research on the molecular basis of epilepsy, the essential players in the epileptogenic process leading to epilepsy are not known. Gene expression analysis is one strategy to enhance our understanding of the genes contributing to the functional neuronal changes underlying epileptogenesis. In the present study, we used the novel MPSS (massively parallel signature sequencing) method for analysis of gene expression in the rat kindling model of temporal lobe epilepsy. Kindling by repeated electrical stimulation of the amygdala resulted in the differential expression of 264 genes in the hippocampus compared to sham controls. The most strongly induced gene was Homer 1A, an immediate early gene involved in the modulation of glutamate receptor function. The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT-PCR. In order to evaluate the functional implications of Homer 1A overexpression for kindling, we used transgenic mice that permanently overexpress Homer 1A. Immunohistochemical characterization of these mice showed a marked Homer 1A overexpression in glutamatergic neurons of the hippocampus. Kindling of Homer 1A overexpressing mice resulted in a retardation of seizure generalization compared to wild-type controls. The data demonstrate that kindling-induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease.

Original languageEnglish (US)
Pages (from-to)2157-2165
Number of pages9
JournalEuropean Journal of Neuroscience
Volume16
Issue number11
DOIs
StatePublished - Dec 24 2002

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Keywords

  • Epilepsy
  • Gene expression
  • Glutamate
  • Hippocampus
  • Homer
  • Kindling
  • Mice
  • Rats

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Potschka, H., Krupp, E., Ebert, U., Gümbel, C., Leichtlein, C., Lorch, B., Pickert, A., Kramps, S., Young, K., Grüne, U., Keller, A., Welschof, M., Vogt, G., Xiao, B., Worley, P. F., Löscher, W., & Hiemisch, H. (2002). Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. European Journal of Neuroscience, 16(11), 2157-2165. https://doi.org/10.1046/j.1460-9568.2002.02265.x