title: Experimental febrile seizures impair interastrocytic gap junction coupling in juvenile mice.
abstract: Prolonged and focal febrile seizures (FSs) have been associated with the development of temporal lobe epilepsy (TLE), although the underlying mechanism and the contribution of predisposing risk factors are still poorly understood. Using a kainate model of TLE, we previously provided strong evidence that interruption of astrocyte gap junction-mediated intercellular communication represents a crucial event in epileptogenesis. To elucidate this aspect further, we induced seizures in immature mice by hyperthermia (HT) to study the consequences of FSs on the hippocampal astrocytic network. Changes in interastrocytic coupling were assessed by tracer diffusion studies in acute slices from mice 5 days after experimental FS induction. The results reveal that HT-induced FSs cause a pronounced reduction of astrocyte gap junctional coupling in the hippocampus by more than 50%. Western blot analysis indicated that reduced connexin43 protein expression and/or changes in the phosphorylation status account for this astrocyte dysfunction. Remarkably, uncoupling occurred in the absence of neuronal death and reactive gliosis. These data provide a mechanistic link between FSs and the subsequent development of TLE and further strengthen the emerging view that astrocytes have a central role in the pathogenesis of this disorder. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
authors.forename: Dilaware
authors.initials: D
authors.lastname: Khan
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dupper
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
authors.forename: Tushar
authors.initials: T
authors.lastname: Deshpande
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Pierre N E De
authors.initials: PN
authors.lastname: Graan
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Steinhäuser
authors.affiliation: Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bedner
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D016923:Cell Death; D018031:Connexin 43 / Q000378:metabolism; D054351:Electrical Synapses / Q000473:pathology*; D004833:Epilepsy, Temporal Lobe / Q000473:pathology; D005334:Fever / Q000473:pathology; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008262:Macrophage Activation; D051379:Mice; D010766:Phosphorylation; D003294:Seizures, Febrile / Q000473:pathology*
chemical_list: D018031:Connexin 43
keywords: astroglia; connexin; epilepsy; gap junctions; hippocampus; hyperthermia