Division of Brain Sciences, Imperial College London, Charing Cross Hospital, W12 0NN London, United Kingdom.
Division of Neuroscience, University Vita-Salute San Raffaele, Milan 20132, Italy.
eNeuro. 2017 Dec 28;4(6). doi: 10.1523/ENEURO.0152-17.2017. eCollection 2017 Nov-Dec.
The identification of mechanisms transforming normal to seizure-generating tissue after brain injury is key to developing new antiepileptogenic treatments. MicroRNAs (miRNAs) may act as regulators and potential treatment targets for epileptogenesis. Here, we undertook a meta-analysis of changes in miRNA expression in the hippocampal dentate gyrus (DG) following an epileptogenic insult in three epilepsy models. We identified 26 miRNAs significantly differentially expressed during epileptogenesis, and five differentially expressed in chronic epilepsy. Of these, 13 were not identified in any of the individual studies. To assess the role of these miRNAs, we predicted their mRNA targets and then filtered the list to include only target genes expressed in DG and negatively correlated with miRNA expression. Functional enrichment analysis of mRNA targets of miRNAs dysregulated during epileptogenesis suggested a role for molecular processes related to inflammation and synaptic function. Our results identify new miRNAs associated with epileptogenesis from existing data, highlighting the utility of meta-analysis in maximizing value from preclinical data.
在脑损伤后识别将正常组织转化为致痫组织的机制是开发新的抗癫痫发生治疗方法的关键。 microRNAs (miRNAs) 可能作为癫痫发生的调节剂和潜在治疗靶点。在这里,我们对三种癫痫模型中海马齿状回 (DG) 中 miRNA 表达的变化进行了荟萃分析。我们鉴定了在癫痫发生过程中显著差异表达的 26 个 miRNA,以及在慢性癫痫中差异表达的 5 个 miRNA。其中,有 13 个 miRNA 在任何一个单独的研究中都没有被发现。为了评估这些 miRNA 的作用,我们预测了它们的 mRNA 靶标,然后过滤掉只包括在 DG 中表达且与 miRNA 表达呈负相关的靶基因的列表。对癫痫发生过程中失调的 miRNA 的 mRNA 靶标的功能富集分析表明,与炎症和突触功能相关的分子过程可能起作用。我们的研究结果从现有数据中确定了与癫痫发生相关的新 miRNA,突出了荟萃分析在从临床前数据中最大化价值的作用。