title: Dysregulation of long non-coding RNAs in mouse models of localization-related epilepsy.
abstract: Genome-wide profiling has revealed that eukaryotic genomes are transcribed into numerous non-coding RNAs. In particular, long non-coding RNAs (lncRNAs) have been implicated in various human diseases due to their biochemical and functional diversity. Epileptic disorders have been characterized by dysregulation of epigenetic regulatory mechanisms, and recent studies have identified several lncRNAs involved in neural development and network function. However, comprehensive profiling of lncRNAs implicated in chronic epilepsy has been lacking. In this study, microarray analysis was performed to obtain the expression profile of lncRNAs dysregulated in pilocarpine and kainate models, two models of temporal lobe epilepsy commonly used for studying epileptic mechanisms. Total of 4622 lncRNAs were analyzed: 384 lncRNAs were significantly dysregulated in pilocarpine model, and 279 lncRNAs were significantly dysregulated in kainate model compared with control mice (≥3.0-fold, p < 0.05). Among these, 54 and 14 lncRNAs, respectively, had adjacent protein-coding genes whose expressions were also significantly dysregulated (≥2.0-fold, p < 0.05). Majority of these pairs of lncRNAs and adjacent genes shared the same direction of dysregulation. For the selected adjacent gene-lncRNA pairs, significant Gene Ontology terms were embryonic appendage morphogenesis and neuron differentiation. This was the first study to comprehensively identify dysregulated lncRNAs in two different models of chronic epilepsy and will likely provide a novel insight into developing lncRNA therapeutics.
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Doo Young
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jangsup
authors.initials: J
authors.lastname: Moon
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Jung-Seok
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jun-Sang
authors.initials: JS
authors.lastname: Sunwoo
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jung-Ick
authors.initials: JI
authors.lastname: Byun
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Lim
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Jung
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea; Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Daejong
authors.initials: D
authors.lastname: Jeon
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea. Electronic address: stemcell.snu@gmail.com.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Comprehensive Epilepsy Center, Seoul National University Hospital, Seoul, South Korea; Program in Neuroscience, Neuroscience Research Institute of Seoul National University Medical Research Council, College of Medicine, Seoul National University, Seoul, South Korea. Electronic address: sangkun2923@gmail.com.
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics*; D051379:Mice; D010862:Pilocarpine / Q000494:pharmacology; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding; D010862:Pilocarpine
keywords: Epilepsy; Kainate; Microarray; Pilocarpine; lncRNA