AUTHOR=Zhang Lei , Xue Zhenyu , Yan Jia , Jiang Hong 

TITLE=LncRNA Rik-203 Contributes to Sevoflurane Induced Neurotoxicity?

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.00353

DOI=10.3389/fmed.2020.00353

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> The anesthetics inhibit neural differentiation, induce neuron loss and cognitive impairment in young animals. However, the underlying mechanisms of anesthesia on neural differentiation are unknown.</p><p><bold>Methods:</bold> Embryonic stem cells (ESCs) and mice received sevoflurane anesthesia. RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over-expression and RNA interference of genes; flow cytometry; real-time quantity PCR and Western blot were used in the studies. RNA pull-down assay and PCR were employed to detect any miRNA that attached to Rik-203. The binding of miRNA with mRNA of BDNF was presented by the luciferase assay.</p><p><bold>Results:</bold> Here we found that LncRNA Riken-203(Rik-203) was highly expressed in mice brain and was upregulated during neural differentiation. Sevoflurane decreased the amount of Rik-203 in mice brain. Knockdown of Rik-203 repressed the neural differentiation derived from mouse embryonic stem cell and downregulated the neural progenitor cells markers Sox1 and Nestin. RNA pull-down showed that miR-466l-3p was highly bound to Rik-203. Inhibition of miR-466l-3p restored the neural differentiation repressed by Rik-203 knockdown. Brain derived neurotrophic factor (BDNF), which was downregulated by sevoflurane, was also directly targeted by miR-466l-3p. Overexpression of BDNF restored the neural differentiation repressed by miR-466l-3p and Rik-203 knockdown.</p><p><bold>Conclusion:</bold> Our study suggested that sevoflurane related LncRNARik-203 facilitates neural differentiation by inhibiting miR-466l-3p's ability to reduce BDNF levels.</p>