Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, P.R. China.
Shanghai Tenth People's Hospital, Anesthesia and Brain Research Institute, Tongji University School of Medicine, Shanghai, P.R. China.
Sci Rep. 2019 May 2;9(1):6822. doi: 10.1038/s41598-019-42991-4.
The mechanism of anesthesia neurotoxicity remains largely to be determined. The effects of long noncoding RNAs (LncRNAs) on neural differentiation and the underlying mechanisms are unknown. We thus identified LncRNA Rik-203 (C130071C03Rik) and studied its role on neural differentiation and its interactions with anesthetic sevoflurane, miRNA and GSK-3β. We found that levels of Rik-203 were higher in hippocampus than other tissues and increased during neural differentiation. Sevoflurane decreased the levels of Rik-203. Rik-203 knockdown reduced mRNA levels of Sox1 and Nestin, the markers of neural progenitor cells, and decreased the count of Sox1 positive cells. RNA-RNA pull-down showed that miR-101a-3p was highly bound to Rik-203. Finally, sevoflurane, knockdown of Rik-203, and miR-101a-3p overexpression all decreased GSK-3β levels. These data suggest that Rik-203 facilitates neural differentiation by inhibiting miR-101a-3p's ability to reduce GSK-3β levels and that LncRNAs would serve as the mechanism of the anesthesia neurotoxicity.
麻醉神经毒性的机制在很大程度上仍有待确定。长链非编码 RNA（LncRNA）对神经分化的影响及其潜在机制尚不清楚。因此，我们鉴定了 LncRNA Rik-203（C130071C03Rik），并研究了它在神经分化中的作用及其与麻醉剂七氟醚、miRNA 和 GSK-3β的相互作用。我们发现 Rik-203 在海马体中的水平高于其他组织，并在神经分化过程中增加。七氟醚降低了 Rik-203 的水平。Rik-203 的敲低降低了神经祖细胞标志物 Sox1 和 Nestin 的 mRNA 水平，并减少了 Sox1 阳性细胞的数量。RNA-RNA 下拉显示 miR-101a-3p 与 Rik-203 高度结合。最后，七氟醚、Rik-203 的敲低和 miR-101a-3p 的过表达均降低了 GSK-3β 的水平。这些数据表明，Rik-203 通过抑制 miR-101a-3p 降低 GSK-3β 水平的能力促进神经分化，并且 LncRNA 将作为麻醉神经毒性的机制。
