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.