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Sevoflurane induces microRNA-18a to delay rat neurodevelopment via suppression of the RUNX1/Wnt/β-catenin axis
Cell Death Discovery ( IF 6.1 ) Pub Date : 2022-10-01 , DOI: 10.1038/s41420-022-01179-y
Yuge Jiang 1 , Yaobo Liu 2 , Yuhui Sun 2 , Yongzhe Liu 3 , Long Feng 4 , Mingda Duan 4 , Yi Liu 3, 4 , Longhe Xu 3, 4
Affiliation  

Sevoflurane anesthesia is reported to repress neurogenesis of neural stem cells (NSCs), thereby affecting the brain development, but the underlying mechanism of sevoflurane on the proliferation of NSCs remains unclear. Thus, this study aims to discern the relationship between sevoflurane and NSC proliferation. Bioinformatics tools were employed to predict the expression of microRNA-18a (miR-18a) in 9-day-old neonatal rat hippocampal tissues after sevoflurane treatment and the downstream genes of miR-18a, followed by a series of assays to explore the relationship among miR-18a, runt related transcription factor 1 (RUNX1), and β-catenin in the hippocampal tissues. NSCs were isolated from the hippocampal tissues and subjected to gain-/loss-of-function assays to investigate the interactions among miR-18a, RUNX1, and β-catenin in NSCs and their roles in NSC development. Bioinformatics analysis and experimental results confirmed high expression of miR-18a in rat hippocampal tissues and NSCs after sevoflurane treatment. Next, we found that miR-18a downregulated RUNX1 expression, while RUNX1 promoted NSC proliferation by activating the Wnt/β-catenin signaling pathway. The behavioral experiments also showed that sevoflurane caused nerve injury in rats, whilst RUNX1 overexpression protected rat neurodevelopment. Our findings uncovered that sevoflurane attenuated NSC proliferation via the miR-18a-meidated RUNX1/Wnt/β-catenin pathway, thereby impairing rat neurodevelopment.



中文翻译:

七氟醚通过抑制 RUNX1/Wnt/β-catenin 轴诱导 microRNA-18a 延迟大鼠神经发育

据报道,七氟醚麻醉可抑制神经干细胞 (NSCs) 的神经发生,从而影响大脑发育,但七氟醚对 NSCs 增殖的潜在机制仍不清楚。因此,本研究旨在辨别七氟醚与 NSC 增殖之间的关系。采用生物信息学工具预测七氟醚处理后9日龄新生大鼠海马组织中microRNA-18a(miR-18a)的表达和miR-18a下游基因的表达,随后进行了一系列检测,探讨了两者之间的关系。海马组织中的 miR-18a、runt 相关转录因子 1 (RUNX1) 和 β-连环蛋白。从海马组织中分离出 NSC,并进行功能获得/丧失测定,以研究 miR-18a、RUNX1、NSC中的β-catenin及其在NSC发育中的作用。生物信息学分析和实验结果证实了七氟醚处理后大鼠海马组织和神经干细胞中 miR-18a 的高表达。接下来,我们发现 miR-18a 下调 RUNX1 的表达,而 RUNX1 通过激活 Wnt/β-catenin 信号通路促进 NSC 增殖。行为实验还表明,七氟醚会导致大鼠神经损伤,而 RUNX1 过表达保护大鼠神经发育。我们的研究结果发现,七氟醚通过 miR-18a 介导的 RUNX1/Wnt/β-catenin 通路减弱 NSC 增殖,从而损害大鼠神经发育。我们发现 miR-18a 下调 RUNX1 的表达,而 RUNX1 通过激活 Wnt/β-catenin 信号通路促进 NSC 增殖。行为实验还表明,七氟醚会导致大鼠神经损伤,而 RUNX1 过表达保护大鼠神经发育。我们的研究结果发现,七氟醚通过 miR-18a 介导的 RUNX1/Wnt/β-catenin 通路减弱 NSC 增殖,从而损害大鼠神经发育。我们发现 miR-18a 下调 RUNX1 的表达,而 RUNX1 通过激活 Wnt/β-catenin 信号通路促进 NSC 增殖。行为实验还表明,七氟醚会导致大鼠神经损伤,而 RUNX1 过表达保护大鼠神经发育。我们的研究结果发现,七氟醚通过 miR-18a 介导的 RUNX1/Wnt/β-catenin 通路减弱 NSC 增殖,从而损害大鼠神经发育。

更新日期:2022-10-01
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