title: Epilepsy-induced motility of differentiated neurons.
abstract: Neuronal ectopia, such as granule cell dispersion (GCD) in temporal lobe epilepsy (TLE), has been assumed to result from a migration defect during development. Indeed, recent studies reported that aberrant migration of neonatal-generated dentate granule cells (GCs) increased the risk to develop epilepsy later in life. On the contrary, in the present study, we show that fully differentiated GCs become motile following the induction of epileptiform activity, resulting in GCD. Hippocampal slice cultures from transgenic mice expressing green fluorescent protein in differentiated, but not in newly generated GCs, were incubated with the glutamate receptor agonist kainate (KA), which induced GC burst activity and GCD. Using real-time microscopy, we observed that KA-exposed, differentiated GCs translocated their cell bodies and changed their dendritic organization. As found in human TLE, KA application was associated with decreased expression of the extracellular matrix protein Reelin, particularly in hilar interneurons. Together these findings suggest that KA-induced motility of differentiated GCs contributes to the development of GCD and establish slice cultures as a model to study neuronal changes induced by epileptiform activity.
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chai
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Münzner
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Shanting
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Tinnes
authors.affiliation: Institute of Science and Technology (IST) Austria, Klosterneuburg, Austria.
authors.forename: Janina
authors.initials: J
authors.lastname: Kowalski
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Häussler
authors.affiliation: Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Young
authors.affiliation: Experimental Epilepsy Research, Department of Neurosurgery, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Carola A
authors.initials: CA
authors.lastname: Haas
authors.affiliation: Institute for Structural Neurobiology, Center for Molecular Neurobiology Hamburg (ZMNH), Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany michael.frotscher@zmnh.uni-hamburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Frotscher
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D066146:Cell Body / Q000473:pathology / Q000502:physiology; D002465:Cell Movement; D003712:Dendrites / Q000502:physiology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000473:pathology / Q000502:physiology; D007608:Kainic Acid; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000091042:Reelin Protein; D049452:Green Fluorescent Proteins; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D007608:Kainic Acid
keywords: dentate gyrus; granule cell dispersion; real-time microscopy; reelin; somal translocation