Surges Rainer, Kretschmann Anita, Abnaof Khalid, van Rikxoort Marijke, Ridder Kirsten, Fröhlich Holger, Danis Bénédicte, Kaminski Rafal M, Foerch Patrik, Elger Christian E, Weinsberg Frank, Pfeifer Alexander
Department of Epileptology, University Hospital of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Biochem Biophys Res Commun. 2016 Dec 2;481(1-2):13-18. doi: 10.1016/j.bbrc.2016.11.029. Epub 2016 Nov 8.
MicroRNAs (miRNAs) are key regulators of gene expression and are involved in the pathomechanisms of epilepsy. MiRNAs may also serve as peripheral biomarkers of epilepsy. We investigated the miRNA profile in the blood serum of patients suffering from mesial temporal lobe epilepsy (mTLE) following a single focal seizure evolving to a bilateral convulsive seizure (BCS) during video-EEG monitoring. Data of 15 patients were included in the final analysis. MiRNA expression was determined using Real Time-PCR followed by thorough bioinformatical analysis of expression levels. We found that more than 200 miRNAs were differentially expressed in the serum of patients within 30 min after a single seizure. Validation of the 20 top miRNA candidates confirmed that 4 miRNAs (miR-143, miR-145, miR-532, miR-365a) were significantly deregulated. Interestingly, in a sub-group of patients with seizures occurring during sleep, we found 10 miRNAs to be deregulated up to 20-28 h after the seizure. In this group of patients, miR-663b was significantly deregulated. We conclude that single seizures are associated with detectable transient miRNA alterations in blood serum in the early postictal phase. The significant upregulation of miR-663b following BCS arising during sleep indicates potential suitability of this miRNA as a potential biomarker for seizure diagnostics.
微小RNA（miRNA）是基因表达的关键调节因子，参与癫痫的发病机制。miRNA也可能作为癫痫的外周生物标志物。我们研究了在视频脑电图监测期间，单次局灶性发作演变为双侧惊厥性发作（BCS）的内侧颞叶癫痫（mTLE）患者血清中的miRNA谱。最终分析纳入了15例患者的数据。使用实时定量聚合酶链反应（Real Time-PCR）测定miRNA表达，随后对表达水平进行全面的生物信息学分析。我们发现，单次发作后30分钟内，患者血清中有200多种miRNA表达存在差异。对20个最具候选性的miRNA进行验证，证实4种miRNA（miR-143、miR-145、miR-532、miR-365a）有明显失调。有趣的是，在睡眠期间发作的患者亚组中，我们发现发作后20 - 28小时内有10种miRNA失调。在这组患者中，miR-663b有明显失调。我们得出结论，单次发作与发作后早期血清中可检测到的短暂miRNA改变有关。睡眠期间发生BCS后miR-663b的显著上调表明，这种miRNA有可能作为癫痫诊断的潜在生物标志物。
