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Experimental Brain Research

, Volume 200, Issue 2, pp 141–149 | Cite as

Reelin deficiency causes granule cell dispersion in epilepsy

  • Carola A. Haas
  • Michael Frotscher
Review

Abstract

Cortical migration defects are often associated with epilepsy. In mesial temporal lobe epilepsy (MTLE), granule cell dispersion (GCD), a migration defect of dentate granule cells, is frequently observed. Little is known how GCD develops and to which extent it contributes to the development of seizure activity. Since the reelin-deficient reeler mouse mutant shows a similar migration defect of dentate cells, we performed a series of studies investigating whether reelin deficiency is involved in GCD development. We show that in MTLE patients and in a mouse model of MTLE, the development of GCD correlates with a loss of the extracellular matrix protein reelin. In addition, we present evidence that GCD occurs in the absence of neurogenesis, thus representing a displacement of mature neurons due to a reelin deficiency. Accordingly, antibody blockade of reelin function in naïve, adult mice induced GCD. Finally, we show that GCD formation can be prevented by infusion of exogenous reelin. In summary, these studies show that in epilepsy reelin dysfunction causes GCD development and that reelin is important for the maintenance of layered structures in the adult brain.

Keywords

Hippocampus Neuronal migration Neurogenesis Dentate gyrus Seizure Mouse 

Notes

Acknowledgments

The authors thank all those who contributed with their time and talents to the studies reviewed in this article. In particular, we thank M. Müller, M. Osswald, C. Heinrich, U. Häussler, A. Jacobi, A. Fahrner, E. Förster, and S. Huber for their contributions. This work was supported by the Deutsche Forschungsgemeinschaft (SFB TR 3).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Experimental Epilepsy Research, NeurocenterUniversity of FreiburgFreiburgGermany
  2. 2.Institute of Anatomy and Cell BiologyUniversity of FreiburgFreiburgGermany

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