Huang Li-Gang, Zou Jing, Lu Qin-Chi
Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Brain Res. 2018 Jun 15;1689:109-122. doi: 10.1016/j.brainres.2017.11.019. Epub 2017 Nov 28.
Temporal lobe epilepsy (TLE) is a chronic neurological disease characterized by recurrent spontaneous seizures. MicroRNAs are dysregulated in various pathological conditions including epilepsy. Therefore, we hypothesized that the dysregulation of these microRNAs might also be associated with the pathogenesis of TLE. In this study, we found that a microRNA, hsa-miR-155-5p, was upregulated in patients with TLE post-surgery, and hence associated with clinical and pathological manifestations and seizure outcomes. We then used a rat model of experimental epilepsy induced by pilocarpine and revealed that the rat homologue was upregulated as well. Importantly, injection of an antagomiR of rno-miR-155-5p in vivo resulted in a reduction of the pathophysiological features associated with the status epilepticus, which was accompanied by decrease of apoptosis in the hippocampus. This effect was correlated with an increase in rat Sestrin-3 expression, which was a gene known to counteract oxidative stress. This rescue was also observed after injection of a lentivirus carrying the small interfering RNA of rat Sestrin-3 gene in the hippocampus. In addition, rno-miR-155-5p as well as rat Sestrin-3 mRNA and protein expression were partly dependent on oxidative stress induced by HO in PC12 cells Taken together, our data suggest that rno-miR-155-5p is a potent post-transcriptional regulator of rat Sestrin-3 and it may be one of the molecular links between brain damage and increased risk for seizures during damage by oxidative stress.
颞叶癫痫（TLE）是一种以反复自发性癫痫发作为特征的慢性神经疾病。微小RNA在包括癫痫在内的各种病理状况下均存在失调。因此，我们推测这些微小RNA的失调可能也与TLE的发病机制相关。在本研究中，我们发现一种微小RNA，即hsa-miR-155-5p，在TLE患者术后上调，因此与临床和病理表现以及癫痫发作结果相关。然后我们使用毛果芸香碱诱导的实验性癫痫大鼠模型，发现大鼠同源物也上调。重要的是，在体内注射rno-miR-155-5p的反义寡核苷酸导致与癫痫持续状态相关的病理生理特征减少，同时海马区细胞凋亡减少。这种效应与大鼠Sestrin-3表达增加相关，Sestrin-3是一种已知可对抗氧化应激的基因。在海马区注射携带大鼠Sestrin-3基因小干扰RNA的慢病毒后也观察到了这种挽救作用。此外，rno-miR-155-5p以及大鼠Sestrin-3的mRNA和蛋白表达部分依赖于PC12细胞中HO诱导的氧化应激。综上所述，我们的数据表明rno-miR-155-5p是大鼠Sestrin-3的一种有效的转录后调节因子，它可能是脑损伤与氧化应激损伤期间癫痫发作风险增加之间的分子联系之一。
