title: Etiology matters - Genomic DNA Methylation Patterns in Three Rat Models of Acquired Epilepsy.
abstract: This study tested the hypothesis that acquired epileptogenesis is accompanied by DNA methylation changes independent of etiology. We investigated DNA methylation and gene expression in the hippocampal CA3/dentate gyrus fields at 3 months following epileptogenic injury in three experimental models of epilepsy: focal amygdala stimulation, systemic pilocarpine injection, or lateral fluid-percussion induced traumatic brain injury (TBI) in rats. In the models studies, DNA methylation and gene expression profiles distinguished controls from injured animals. We observed consistent increased methylation in gene bodies and hypomethylation at non-genic regions. We did not find a common methylation signature in all three different models and few regions common to any two models. Our data provide evidence that genome-wide alteration of DNA methylation signatures is a general pathomechanism associated with epileptogenesis and epilepsy in experimental animal models, but the broad pathophysiological differences between models (i.e. pilocarpine, amygdala stimulation, and post-TBI) are reflected in distinct etiology-dependent DNA methylation patterns.
authors.affiliation: Laboratory of Epileptogenesis, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Konrad J
authors.initials: KJ
authors.lastname: Dębski
authors.affiliation: Epilepsy Research Laboratory, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Asla
authors.initials: A
authors.lastname: Pitkanen
authors.affiliation: Epilepsy Research Laboratory, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Puhakka
authors.affiliation: Laboratory of Epileptogenesis, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bot
authors.affiliation: Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia.
authors.forename: Ishant
authors.initials: I
authors.lastname: Khurana
authors.affiliation: Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia.
authors.forename: K N
authors.initials: KN
authors.lastname: Harikrishnan
authors.affiliation: Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Ziemann
authors.affiliation: Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia.
authors.forename: Antony
authors.initials: A
authors.lastname: Kaspi
authors.affiliation: Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia.
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
authors.affiliation: Laboratory of Epileptogenesis, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lukasiuk
authors.affiliation: Department of Neuropathology, University Hospital Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kobow
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D019175:DNA Methylation / Q000235:genetics*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D016678:Genome; D008297:Male; D058977:Molecular Sequence Annotation; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger