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13-01-2024 | Sevoflurane | Research Article

MiR-181a-5p knockdown ameliorates sevoflurane anesthesia-induced neuron injury via regulation of the DDX3X/Wnt/β-catenin signaling axis

Authors: Yuqi She, Zhijun Chen, Li Zhang, Yuan Wang

Published in: Experimental Brain Research | Issue 3/2024

Abstract

Sevoflurane is one of the most widely used inhaled anesthetics. MicroRNAs (miRNAs) have been demonstrated to affect sevoflurane anesthesia-induced neuron damage. The purpose of this study was to investigate the role and mechanism of miR-181a-5p in sevoflurane-induced hippocampal neuronal injury. Primary hippocampal neurons were identified using microscopy and immunofluorescence. The viability and apoptosis of sevoflurane anesthesia-induced neurons were detected by cell counting kit-8 (CCK-8) assay and terminal-deoxynucleoitidyl transferase-mediated nick end-labeling (TUNEL) staining assay, respectively. The levels of apoptosis- and oxidative stress-related proteins as well as the markers in the Wnt/β-catenin signaling pathway were examined by immunoblotting. Enzyme-linked immuno-sorbent assays were performed to examine the levels of inflammatory cytokines. Luciferase reporter assay was conducted to validate the combination between miR-181a-5p and DEAD-box helicase 3, X-linked (DDX3X). Sevoflurane exposure led to significantly inhibited hippocampal neuron viability and elevated miR-181a-5p expression. Knockdown of miR-181a-5p alleviated sevoflurane-induced neuron injury by reducing cell apoptosis, inflammatory response, and oxidative stress. Additionally, DDX3X was targeted and negatively regulated by miR-181a-5p. Moreover, miR-181a-5p inhibitor activated the Wnt/β-catenin pathway via DDX3X in sevoflurane-treated cells. Rescue experiments revealed that DDX3X knockdown or overexpression of Wnt antagonist Dickkopf-1 (DKK1) reversed the suppressive effects of miR-181a-5p inhibitor on cell apoptosis, inflammatory response, and oxidative stress in sevoflurane-treated neuronal cells. MiR-181a-5p ameliorated sevoflurane-triggered neuron injury by regulating the DDX3X/Wnt/β-catenin axis, suggesting the potential of miR-181a-5p as a novel and promising therapeutic target for the treatment of sevoflurane-evoked neurotoxicity.

Ansari A et al (2019) miR-146a and miR-181a are involved in the progression of mild cognitive impairment to Alzheimer’s disease. Neurobiol Aging 82:102–109PubMedCrossRefMATH

Beekoo D et al (2019) Analyzing electroencephalography (EEG) waves provides a reliable tool to assess the depth of sevoflurane anesthesia in pediatric patients. Med Sci Monit 25:4035–4040PubMedPubMedCentralCrossRefMATH

Boitnott A et al (2021) Developmental and behavioral phenotypes in a mouse model of DDX3X syndrome. Biol Psychiatry 90(11):742–755PubMedPubMedCentralCrossRefMATH

Bono B et al (2020) Novel insights into the biochemical mechanism of CK1ε and its functional interplay with DDX3X. Int J Mol Sci 21(17):6449PubMedPubMedCentralCrossRefMATH

Chen X et al (2016a) Aberrantly expressed long noncoding RNAs are involved in sevoflurane-induced developing hippocampal neuronal apoptosis: a microarray related study. Metab Brain Dis 31(5):1031–1040PubMedCrossRefMATH

Chen HH, Yu HI, Tarn WY (2016b) DDX3 modulates neurite development via translationally activating an RNA regulon involved in Rac1 activation. J Neurosci 36(38):9792–9804PubMedPubMedCentralCrossRef

Chen WJ et al (2017) DDX3 localizes to the centrosome and prevents multipolar mitosis by epigenetically and translationally modulating p53 expression. Sci Rep 7(1):9411ADSPubMedPubMedCentralCrossRefMATH

Christopher AF et al (2016) MicroRNA therapeutics: discovering novel targets and developing specific therapy. Perspect Clin Res 7(2):68–74MathSciNetPubMedPubMedCentralCrossRefMATH

Cruciat CM et al (2013) RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-β-catenin signaling. Science 339(6126):1436–1441ADSPubMedCrossRef

Fang F, Xue Z, Cang J (2012) Sevoflurane exposure in 7-day-old rats affects neurogenesis, neurodegeneration and neurocognitive function. Neurosci Bull 28(5):499–508PubMedPubMedCentralCrossRef

Feng D et al (2022) DDX3X alleviates doxorubicin-induced cardiotoxicity by regulating Wnt/β-catenin signaling pathway in an in vitro model. J Biochem Mol Toxicol 36:e23077PubMedPubMedCentralCrossRef

Flick RP et al (2011) Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics 128(5):e1053–e1061PubMedPubMedCentralCrossRefMATH

Foresta C, Ferlin A, Moro E (2000) Deletion and expression analysis of AZFa genes on the human Y chromosome revealed a major role for DBY in male infertility. Hum Mol Genet 9(8):1161–1169PubMedCrossRefMATH

Geng R et al (2021) Venlafaxine inhibits the apoptosis of SHSY-5Y cells through active Wnt/β-catenin signaling pathway. Neuropsychiatr Dis Treat 17:1145–1151PubMedPubMedCentralCrossRef

He C et al (2021) miR-485-5p alleviates Alzheimer’s disease progression by targeting PACS1. Transl Neurosci 12(1):335–345PubMedPubMedCentralCrossRef

van Heerma Voss MR et al (2015) Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer. Oncotarget 6(29):28312–28326CrossRef

Hou D et al (2018) Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer. Redox Biol 17:99–111PubMedPubMedCentralCrossRefMATH

Hu Z, Li Z (2017) miRNAs in synapse development and synaptic plasticity. Curr Opin Neurobiol 45:24–31PubMedPubMedCentralCrossRefMATH

Hwang DS et al (2017) Dangguijakyak-san ameliorates memory deficits in ovariectomized mice by upregulating hippocampal estrogen synthesis. BMC Complement Altern Med 17(1):501PubMedPubMedCentralCrossRefMATH

Indrieri A et al (2019) miR-181a/b downregulation exerts a protective action on mitochondrial disease models. EMBO Mol Med. https://doi.org/10.15252/emmm.201708734CrossRefPubMedPubMedCentral

Ishikawa M et al (2012) Differences in microRNA changes of healthy rat liver between sevoflurane and propofol anesthesia. Anesthesiology 117(6):1245–1252PubMedCrossRefMATH

Jankowsky A, Guenther UP, Jankowsky E (2011) The RNA helicase database. Nucleic Acids Res 39:D338–D341PubMedCrossRef

Jeong JK et al (2014) Melatonin-mediated β-catenin activation protects neuron cells against prion protein-induced neurotoxicity. J Pineal Res 57(4):427–434PubMedCrossRef

Kaga S et al (2006) Glycogen synthase kinase-3beta/beta-catenin promotes angiogenic and anti-apoptotic signaling through the induction of VEGF, Bcl-2 and survivin expression in rat ischemic preconditioned myocardium. J Mol Cell Cardiol 40(1):138–147PubMedCrossRef

Kahn M (2014) Can we safely target the WNT pathway? Nat Rev Drug Discov 13(7):513–532PubMedPubMedCentralCrossRefMATH

Kong H et al (2020) Inhibition of miR-181a-5p reduces astrocyte and microglia activation and oxidative stress by activating SIRT1 in immature rats with epilepsy. Lab Invest 100(9):1223–1237PubMedCrossRef

Li D et al (2022) The protective effects of miR-128-3p on sevoflurane-induced progressive neurotoxicity in rats by targeting NOVA1. J Toxicol Sci 47(2):51–60PubMedCrossRef

Li X et al (2021) miR-335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson’s disease Int J Mol Med. 47(4):61CrossRefPubMedPubMedCentral

Liu G, Sun Y, Liu F (2021a) Curcumin reduces neuroinflammation and improves the impairments of anesthetics on learning and memory by regulating the expression of miR-181a-5p. NeuroImmunoModulation 28(1):38–46PubMedCrossRefMATH

Liu F et al (2021b) Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2. Mol Med 27(1):12PubMedPubMedCentralCrossRef

Lu Y et al (2016a) Neuronal apoptosis may not contribute to the long-term cognitive dysfunction induced by a brief exposure to 2% sevoflurane in developing rats. Biomed Pharmacother 78:322–328PubMedCrossRefMATH

Lu J et al (2016b) Knockout of programmed cell death 5 (PDCD5) gene attenuates neuron injury after middle cerebral artery occlusion in mice. Brain Res 1650:152–161ADSPubMedCrossRef

Lv X et al (2017) MicroRNA-27a-3p suppression of peroxisome proliferator-activated receptor-γ contributes to cognitive impairments resulting from sevoflurane treatment. J Neurochem 143(3):306–319PubMedCrossRefMATH

MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17(1):9–26PubMedPubMedCentralCrossRefMATH

Middlebrooks EH et al (2017) The hippocampus: detailed assessment of normative two-dimensional measurements, signal intensity, and subfield conspicuity on routine 3T T2-weighted sequences. Surg Radiol Anat 39(10):1149–1159PubMedCrossRefMATH

Moon JM, Xu L, Giffard RG (2013) Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss. J Cereb Blood Flow Metab 33(12):1976–1982PubMedPubMedCentralCrossRefMATH

Ouyang YB et al (2012) miR-181 targets multiple Bcl-2 family members and influences apoptosis and mitochondrial function in astrocytes. Mitochondrion 12(2):213–219PubMedCrossRefMATH

Park JH et al (2010) Melittin suppresses PMA-induced tumor cell invasion by inhibiting NF-kappaB and AP-1-dependent MMP-9 expression. Mol Cells 29(2):209–215PubMedCrossRefMATH

Shan L et al (2017) miRNAs may regulate GABAergic transmission associated genes in aged rats with anesthetics-induced recognition and working memory dysfunction. Brain Res 1670:191–200ADSPubMedCrossRef

Song X, Xue Y, Cai H (2021) Down-regulation of miR-181a-5p prevents cerebral ischemic injury by upregulating En2 and activating Wnt/β-catenin pathway. J Stroke Cerebrovasc Dis 30(3):105485PubMedCrossRef

Tian XS et al (2015) Surgical stress induces brain-derived neurotrophic factor reduction and postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation in aged mice. CNS Neurosci Ther 21(5):398–409PubMedPubMedCentralCrossRefMATH

Wang Y et al (2017) Sevoflurane anesthesia in pregnant rats negatively affects nerve function in offspring potentially via inhibition of the Wnt/β-catenin pathway. Mol Med Rep 15(5):2753–2759PubMedCrossRefMATH

Wang F et al (2021) Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/β-Catenin/CaMKIV pathway. J Pharmacol Sci 146(2):105–115PubMedCrossRef

Warboys CM et al (2014) Bidirectional cross-regulation between the endothelial nitric oxide synthase and β-catenin signalling pathways. Cardiovasc Res 104(1):116–126PubMedPubMedCentralCrossRef

Xu LJ et al (2015) Post-stroke treatment with miR-181 antagomir reduces injury and improves long-term behavioral recovery in mice after focal cerebral ischemia. Exp Neurol 264:1–7PubMedCrossRef

Xu L et al (2020) MicroRNA-325-3p prevents sevoflurane-induced learning and memory impairment by inhibiting Nupr1 and C/EBPβ/IGFBP5 signaling in rats. Aging (albany NY) 12(6):5209–5220PubMedCrossRefMATH

Xu D et al (2022) MicroRNA-367-3p suppresses sevoflurane-induced adult rat astrocyte apoptosis by targeting BCL2L11. Exp Ther Med 23(1):9MathSciNetPubMedCrossRef

Ye J et al (2016) Altered hippocampal microRNA expression profiles in neonatal rats caused by sevoflurane anesthesia: MicroRNA profiling and bioinformatics target analysis. Exp Ther Med 12(3):1299–1310PubMedPubMedCentralCrossRef

Zhang Y et al (2013) Sevoflurane inhibits neurogenesis and the Wnt-catenin signaling pathway in mouse neural progenitor cells. Curr Mol Med 13(9):1446–1454PubMedCrossRefMATH

Zhang J, Cheng XY, Sheng GY (2014) AP4M1 is abnormally expressed in oxygen-glucose deprived hippocampal neurons. Neurosci Lett 563:85–89PubMedCrossRef

Zhang DX et al (2017) Neuroprotective effects of erythropoietin against sevoflurane-induced neuronal apoptosis in primary rat cortical neurons involving the EPOR-Erk1/2-Nrf2/Bach1 signal pathway. Biomed Pharmacother 87:332–341PubMedCrossRef

Zhang X et al (2020) Ketamine exerts neurotoxic effects on the offspring of pregnant rats via the Wnt/β-catenin pathway. Environ Sci Pollut Res Int 27(1):305–314MathSciNetPubMedCrossRef

Zhao Y, Ai Y (2020) Overexpression of lncRNA Gm15621 alleviates apoptosis and inflammation response resulting from sevoflurane treatment through inhibiting miR-133a/Sox4. J Cell Physiol 235(2):957–965PubMedCrossRefMATH

Zhao Y et al (2014) Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer’s disease (AD) and in primary human neuronal-glial (HNG) cells. Mol Neurobiol 50(1):97–106PubMedCrossRef

Zhou X et al (2016) Dose-dependent effects of sevoflurane exposure during early lifetime on apoptosis in hippocampus and neurocognitive outcomes in Sprague–Dawley rats. Int J Physiol Pathophysiol Pharmacol 8(3):111–119PubMedPubMedCentralMATH

Zhou HS et al (2021a) Hirsutanol A exhibits neuroprotective activities against sevoflurane-induced neurotoxicity in aged rats. Anat Rec (hoboken) 304(3):591–601PubMedCrossRefMATH

Zhou Y et al (2021b) Downregulation of miR-181a-5p alleviates oxidative stress and inflammation in coronary microembolization-induced myocardial damage by directly targeting XIAP. J Geriatr Cardiol 18(6):426–439PubMedPubMedCentral

Zhu YZ et al (2016) Parecoxib prevents early postoperative cognitive dysfunction in elderly patients undergoing total knee arthroplasty: a double-blind, randomized clinical consort study. Medicine (baltimore) 95(28):e4082PubMedCrossRef

Title: MiR-181a-5p knockdown ameliorates sevoflurane anesthesia-induced neuron injury via regulation of the DDX3X/Wnt/β-catenin signaling axis
Authors: Yuqi She
Zhijun Chen
Li Zhang
Yuan Wang
Publication date: 13-01-2024
Publisher: Springer Berlin Heidelberg
Keyword: Sevoflurane
Published in: Experimental Brain Research / Issue 3/2024
Print ISSN: 0014-4819
Electronic ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-023-06739-x

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MiR-181a-5p knockdown ameliorates sevoflurane anesthesia-induced neuron injury via regulation of the DDX3X/Wnt/β-catenin signaling axis

Abstract

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Springer Medicine

Abstract

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