Dysregulation of long non-coding RNAs in mouse models of localization-related epilepsy

被引:68
作者
Lee, Doo Young [1 ]
Moon, Jangsup [1 ]
Lee, Soon-Tae [1 ,2 ]
Jung, Keun-Hwa [1 ,2 ]
Park, Dong-Kyu [1 ]
Yoo, Jung-Seok [1 ]
Sunwoo, Jun-Sang [1 ,2 ]
Byun, Jung-Ick [1 ,2 ]
Lim, Jung-Ah [1 ,2 ]
Kim, Tae-Joon [1 ]
Jung, Ki-Young [1 ,2 ]
Kim, Manho [1 ,2 ,3 ]
Jeon, Daejong [1 ]
Chu, Kon [1 ,2 ]
Lee, Sang Kun [1 ,2 ]
机构
[1] Seoul Natl Univ Hosp, Dept Neurol, Comprehens Epilepsy Ctr, Lab Neurotherapeut,Biomed Res Inst, Seoul 110744, South Korea
[2] Seoul Natl Univ, Coll Med, Program Neurosci, Med Res Council,Neurosci Res Inst, Seoul, South Korea
[3] Seoul Natl Univ, Coll Med, Prot Metab Med Res Ctr, Seoul, South Korea
关键词
IncRNA; Epilepsy; Pilocarpine; Kainate; Microarray; STATUS EPILEPTICUS; ANIMAL-MODELS; SEIZURES; EXPRESSION; PILOCARPINE; NEUROGENESIS; DISCOVERY; DISEASE; RAT;
D O I
10.1016/j.bbrc.2015.04.149
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 IncRNAs 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 IncRNAs 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 IncRNAs, respectively, had adjacent protein-coding genes whose expressions were also significantly dysregulated (>= 2.0-fold, p < 0.05). Majority of these pairs of IncRNAs and adjacent genes shared the same direction of dysregulation. For the selected adjacent gene-IncRNA pairs, significant Gene Ontology terms were embryonic appendage morphogenesis and neuron differentiation. This was the first study to comprehensively identify dysregulated IncRNAs in two different models of chronic epilepsy and will likely provide a novel insight into developing IncRNA therapeutics. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:433 / 440
页数:8
相关论文
共 31 条
[1]   Epilepsy and brain abnormalities in mice lacking the Otx1 gene [J].
Acampora, D ;
Mazan, S ;
Avantaggiato, V ;
Barone, P ;
Tuorto, F ;
Lallemand, Y ;
Brulet, P ;
Simeone, A .
NATURE GENETICS, 1996, 14 (02) :218-222
[2]   Neuropathologic and Clinical Features of Human Medial Temporal Lobe Epilepsy [J].
Bae, Eun-Kee ;
Jung, Keun-Hwa ;
Chu, Kon ;
Lee, Soon-Tae ;
Kim, Jin-Hee ;
Park, Kyung-Il ;
Kim, Manho ;
Chung, Chun-Ki ;
Lee, Sang Kun ;
Roh, Jae-Kyu .
JOURNAL OF CLINICAL NEUROLOGY, 2010, 6 (02) :73-80
[3]   Key factors in the discovery and development of new antiepileptic drugs [J].
Bialer, Meir ;
White, H. Steve .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (01) :68-82
[4]   Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry [J].
Bond, Allison M. ;
VanGompel, Michael J. W. ;
Sametsky, Evgeny A. ;
Clark, Mary F. ;
Savage, Julie C. ;
Disterhoft, John F. ;
Kohtz, Jhumku D. .
NATURE NEUROSCIENCE, 2009, 12 (08) :1020-U91
[5]   The pilocarpine model of temporal lobe epilepsy [J].
Curia, Giulia ;
Longo, Daniela ;
Biagini, Giuseppe ;
Jones, Roland S. G. ;
Avoli, Massimo .
JOURNAL OF NEUROSCIENCE METHODS, 2008, 172 (02) :143-157
[6]   The global burden and stigma of epilepsy [J].
de Boer, Hanneke M. ;
Mula, Marco ;
Sander, Josernir W. .
EPILEPSY & BEHAVIOR, 2008, 12 (04) :540-546
[7]   Non-coding RNAs in human disease [J].
Esteller, Manel .
NATURE REVIEWS GENETICS, 2011, 12 (12) :861-874
[8]   Widespread ectopic expression of olfactory receptor genes [J].
Feldmesser, Ester ;
Olender, Tsviya ;
Khen, Miriam ;
Yanai, Itai ;
Ophir, Ron ;
Lancet, Doron .
BMC GENOMICS, 2006, 7 (1)
[9]   Treatment of early and late kainic acid-induced status epilepticus with the noncompetitive AMPA receptor antagonist GYKI 52466 [J].
Fritsch, Brita ;
Stott, Jeffrey J. ;
Donofrio, Joy Joelle ;
Rogawski, Michael A. .
EPILEPSIA, 2010, 51 (01) :108-117
[10]   The epidemiology of the comorbidity of epilepsy in the general population [J].
Gaitatzis, A ;
Carroll, K ;
Majeed, A ;
Sander, JW .
EPILEPSIA, 2004, 45 (12) :1613-1622