Reelin deficiency causes granule cell dispersion in epilepsy.
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.
Haas
Carola A
CA
Experimental Epilepsy Research, Neurocenter, University of Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany. carola.haas@uniklinik-freiburg.de
Frotscher
Michael
M
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D004827:Epilepsy / Q000473:pathology / Q000503:physiopathology*; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases