Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
Sci Rep. 2017 Sep 14;7(1):11592. doi: 10.1038/s41598-017-11510-8.
Temporal lobe epilepsy (TLE) is a common chronic neurological disease in humans. A number of studies have demonstrated differential expression of miRNAs in the hippocampus of humans with TLE and in animal models of experimental epilepsy. However, the dissimilarities in experimental design have led to largely discordant results across these studies. Thus, a comprehensive comparison is required in order to better characterize miRNA profiles obtained in various post-status epilepticus (SE) models. We therefore created a database and performed a meta-analysis of differentially expressed miRNAs across 3 post-SE models of epileptogenesis (electrical stimulation, pilocarpine and kainic acid) and human TLE with hippocampal sclerosis (TLE-HS). The database includes data from 11 animal post-SE studies and 3 human TLE-HS studies. A total of 378 differentially expressed miRNAs were collected (274 up-regulated and 198 down-regulated) and analyzed with respect to the post-SE model, time point and animal species. We applied the novel robust rank aggregation method to identify consistently differentially expressed miRNAs across the profiles. It highlighted common and unique miRNAs at different stages of epileptogenesis. The pathway analysis revealed involvement of these miRNAs in key pathogenic pathways underlying epileptogenesis, including inflammation, gliosis and deregulation of the extracellular matrix.
颞叶癫痫（TLE）是人类常见的慢性神经系统疾病。许多研究表明，TLE 患者海马中的 miRNA 表达存在差异，并且在实验性癫痫动物模型中也存在差异。然而，由于实验设计的不同，这些研究的结果存在很大差异。因此，需要进行全面的比较，以更好地描述各种癫痫后状态（SE）模型中获得的 miRNA 图谱。为此，我们创建了一个数据库，并对 3 种癫痫发生（电刺激、匹罗卡品和海人酸）后 SE 模型以及伴有海马硬化的 TLE-HS（TLE 伴海马硬化）的差异表达 miRNA 进行了荟萃分析。该数据库包括来自 11 个动物 SE 后研究和 3 个 TLE-HS 人类研究的数据。共收集了 378 个差异表达的 miRNA（274 个上调和 198 个下调），并根据 SE 后模型、时间点和动物种类进行了分析。我们应用新颖的稳健秩聚合方法来识别图谱中一致差异表达的 miRNA。它突出了在癫痫发生的不同阶段常见和独特的 miRNA。通路分析表明这些 miRNA 参与了癫痫发生的关键致病通路，包括炎症、神经胶质增生和细胞外基质的失调。
