Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China.
Sci Rep. 2017 Aug 31;7(1):10270. doi: 10.1038/s41598-017-10619-0.
Status epilepticus (SE) can cause brain damage and lead to neural dysfunction. Developing novel targets for SE therapy and diagnosis is important and necessary. Previously, we found several differentially expressed microRNAs (miRNAs) in the developing hippocampus following SE, including the autophagy-related miR-96. In the present study, we employed immunofluorescence staining and Western blot analysis to assess the expression of autophagy-related 7 (Atg7) and Atg16L1 and the status of autophagosome formation in the hippocampus of immature rats with SE. Additional in vivo intervention was also performed to investigate the potential therapeutic function of miR-96 in developing rats with SE. We found that Atg7 and Atg16L1 were up-regulated in the neurons after SE, together with an increase in autophagosome formation. Meanwhile, overexpression of miR-96 significantly prevented brain damage in SE rats by inhibiting Atg7 and Atg16L1 expression and autophagosome formation in the hippocampus. Furthermore, Rapamycin negated miR-96 mediated brain injury attenuation through inducing autophagosome formation. Our study indicates that miR-96 might be a potential target for therapy of pediatric SE.
癫痫持续状态（SE）可导致脑损伤，并导致神经功能障碍。开发新的 SE 治疗和诊断靶点是重要且必要的。先前，我们在 SE 后发育中的海马体中发现了几种差异表达的 microRNAs（miRNAs），包括自噬相关的 miR-96。在本研究中，我们通过免疫荧光染色和 Western blot 分析来评估自噬相关 7（Atg7）和 Atg16L1 的表达以及 SE 幼鼠海马体中自噬体形成的状态。还进行了额外的体内干预，以研究 miR-96 在 SE 发育大鼠中的潜在治疗功能。我们发现 SE 后神经元中 Atg7 和 Atg16L1 上调，同时自噬体形成增加。同时，miR-96 的过表达通过抑制海马体中的 Atg7 和 Atg16L1 表达和自噬体形成，显著防止了 SE 大鼠的脑损伤。此外，雷帕霉素通过诱导自噬体形成否定了 miR-96 介导的脑损伤减轻。我们的研究表明，miR-96 可能是小儿 SE 治疗的潜在靶点。
