Sevoflurane-Induced miR-211-5p Promotes Neuronal Apoptosis by Inhibiting Efemp2

Abstract

Sevoflurane exposure can result in serious neurological side effects including neuronal apoptosis and cognitive impairment. Although the microRNA miR-211-5p is profoundly upregulated following sevoflurane exposure in neonatal rodent models, the impact of miR-211-5p on neuronal apoptosis and cognitive impairment postsevoflurane exposure has not yet been elucidated. Here, we found that sevoflurane upregulated miR-211-5p and downregulated EGF-Containing Fibulin Extracellular Matrix Protein 2 (Efemp2, Fibulin-4) levels in vitro and in vivo. Sevoflurane's effect on miR-211-5p expression was based on enhancing primary miR-211 transcription. miR-211-5p targets Efemp2's mRNA 3′-untranslated region, reducing Efemp2 expression. RNA immunoprecipitation revealed significant enrichment of the miR-211-5p:Efemp2 mRNA dyad in the RNA-induced silencing complex. miR-211-5p mimics downregulated Efemp2, leading to phosphorylation of Smad2 and Smad3, upregulation of pro-apoptotic Bim, and mitochondrial release of allograft inflammatory factor 1 and cytochrome C. In contrast, miR-211-5p hairpin inhibitor (AntimiR-211-5p) negatively regulated this apoptotic pathway and reduced neuronal apoptosis in an Efemp2-dependent manner. Sevoflurane-exposed mice administered AntimiR-211-5p displayed reduced cortical apoptosis levels and near-term cognitive impairment. In conclusion, sevoflurane-induced miR-211-5p promotes neuronal apoptosis via Efemp2 inhibition. Summary statement: This study revealed the significance of sevoflurane-induced increases in miR-211-5p on the promotion of neuronal apoptosis via inhibition of Efemp2 and its downstream targets.

Knockdown of UAF1 alleviates sevoflurane-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress

“…SEV has been shown to regulate the expression of non-coding RNAs, such as microRNAs and long noncoding RNAs (lncRNAs) (Shen et al, 2021;Zhao et al, 2021;Jiang et al, 2021;Bao et al, 2021) which play a vital role in the regulation of RNA transcription (Ratti et al, 2020). Thus, we speculate that SEV may upregulate UAF1 transcript and protein levels through regulating the expression of non-coding RNAs.…”

The Effect of Abnormal Regional Homogeneity and Spontaneous Low-Frequency Brain Activity on Lower Cognitive Ability: A Cross-Sectional Study on Postoperative Children With Tetralogy of Fallot

“…Those children require continuous follow up. Furthermore, though recent study on 7-11 years old children who were conducted general anesthesia under 3 has shown that the exposure to general anesthesia in early childhood was not markedly related to the reduced intelligence in later stage (Schuttler et al, 2021), anesthesia was still demonstrated to be a non-negligible factor of cognitive levels in many studies (Pang et al, 2021;Shen et al, 2021;Wu and Zhu, 2021). However, we did not analyze the effect of anesthesia on cognition because of lots of anesthesia data missed.…”

Effects of lncRNA HOXA11-AS on Sevoflurane-Induced Neuronal Apoptosis and Inflammatory Responses by Regulating miR-98-5p/EphA4

“…For example, Xiong et al [ 26 ] found that miR-125b-5p was highly expressed in sevoflurane established rat models, and reduction of miR-125b-5p prevented sevoflurane-induced rat hippocampal cell apoptosis and inflammation. Shen et al [ 27 ] reported that miR-211-5p was significantly increased after treatment with sevoflurane in a neonatal rodent model, and knockdown of miR-211-5p reduced neuronal apoptosis. In our study, double-luciferase results indicate that OXA11-AS targets miR-98-5, and miR-98-5p was lowly expressed in sevoflurane induced neuronal cells and in the hippocampal tissues of animal models ( Figure 3 ).…”