Abstract
The induction of anesthesia in children makes its safety one of the most important global health problems. Neuroinflammation contributes to anesthesia-induced neurotoxicity in young individuals. However, the mechanisms underlying anesthesia-induced neurotoxicity have not been established. In this study, the level of interleukin (IL)-6 in the hippocampus of mice and N2A cells treated with sevoflurane was increased, and long noncoding RNA (LncRNA) Riken was sufficient to decrease sevoflurane-induced neurotoxicity, and the level of inflammatory cytokine IL-6. The RNA pull-down assay verified that miR-101a was bound to lncRNA Riken in N2A cells. In addition, miR-101a blocked the protective effect of lncRNA Riken on anesthesia-induced neuroinflammation. These data suggest that lncRNA Riken attenuated anesthesia-induced neuroinflammation by interacting with microRNA-101a. Finally, we also demonstrated that MAPK phosphatase 1 (MKP-1) was a downstream target of miR-101a, and lncRNA Riken can regulate the expression of MKP-1; the JNK signal transduction pathway has been implicated in sevoflurane-induced IL-6 secretion. Our findings demonstrated that lncRNA Riken alleviated the sevoflurane-induced neurotoxic effects, and the lncRNA Riken/miR-101a/MKP-1/JNK axis plays an important role in the cognitive disorder.
References
Alam A, Hana Z, Jin Z, Suen KC et al (2018) Surgery, neuroinflammation and cognitive impairment. EBioMedicine 37:547–556. https://doi.org/10.1016/j.ebiom.2018.10.021
Amrock LG, Starner ML, Murphy KL, Baxter MG (2015) Long-term effects of single or multiple neonatal sevoflurane exposures on rat hippocampal ultrastructure. Anesthesiology 122:87–95. https://doi.org/10.1097/ALN.0000000000000477
Ang CE, Trevino AE, Chang HY (2020) Diverse lncRNA mechanisms in brain development and disease. Curr Opin Genet Dev 65:42–46. https://doi.org/10.1016/j.gde.2020.05.006
Cai T, Liu Y, Xiao J (2018) Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA-101 in glioblastoma. Cancer Med 7:1404–1415. https://doi.org/10.1002/cam4.1384
Cheng Y, Jiang Y, Zhang L, Wang J et al (2018) Mesenchymal stromal cells attenuate sevoflurane-induced apoptosis in human neuroglioma H4 cells. BMC Anesthesiol 18:84. https://doi.org/10.1186/s12871-018-0553-1
Choi B-H, Hur E-M, Lee J-H, Jun D-J et al (2006) Protein kinase Cdelta-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death. J Cell Sci 119:1329–1340
Collins LM, Downer EJ, Toulouse A, Nolan YM (2015) Mitogen-activated protein kinase phosphatase (MKP)-1 in nervous system development and disease. Mol Neurobiol 51:1158–1167. https://doi.org/10.1007/s12035-014-8786-6
Crapser JD, Spangenberg EE, Barahona RA, Arreola MA et al (2020) Microglia facilitate loss of perineuronal nets in the Alzheimer’s disease brain. EBioMedicine 58:102919. https://doi.org/10.1016/j.ebiom.2020.102919
Du M, Yuan L, Tan X, Huang D et al (2017) The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation. Nat Commun 8:2049. https://doi.org/10.1038/s41467-017-02229-1
Du Y, Du Y, Zhang Y, Huang Z et al (2019) MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer’s disease models. Signal Transduct Target Ther 4:58. https://doi.org/10.1038/s41392-019-0091-4
Evered L, Scott DA (2020) Separating the effects of anaesthesia and surgery on the brain. Br J Anaesth. https://doi.org/10.1016/j.bja.2020.05.036
Gao Y, Liu F, Fang L, Cai R et al (2014) Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages. PLoS ONE 9:e96741. https://doi.org/10.1371/journal.pone.0096741
Gass P, Eckhardt A, Schröder H, Bravo R et al (1996) Transient expression of the mitogen-activated protein kinase phosphatase MKP-1 (3CH134/ERP1) in the rat brain after limbic epilepsy. Brain Res Mol Brain Res 41:74–80
Gui L, Lei X, Zuo Z (2017) Decrease of glial cell-derived neurotrophic factor contributes to anesthesia- and surgery-induced learning and memory dysfunction in neonatal rats. J Mol Med (berl) 95:369–379. https://doi.org/10.1007/s00109-017-1521-9
Guo FX, Wu Q, Li P, Zheng L et al (2019) The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling. Cell Death Differ 26:1670–1687. https://doi.org/10.1038/s41418-018-0235-z
Han Y, Kang C, Kang M, Quan W et al (2019) Long non-coding RNA Mirt2 prevents TNF-alpha-triggered inflammation via the repression of microRNA-101. Int Immunopharmacol 76:105878. https://doi.org/10.1016/j.intimp.2019.105878
Hirotsu A, Iwata Y, Tatsumi K, Miyai Y et al (2019) Maternal exposure to volatile anesthetics induces IL-6 in fetal brains and affects neuronal development. Eur J Pharmacol 863:172682. https://doi.org/10.1016/j.ejphar.2019.172682
Jang S, Kelley KW, Johnson RW (2008) Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci U S A 105:7534–7539. https://doi.org/10.1073/pnas.0802865105
Lee J, Ahn E, Park WK, Park S (2016) Phosphoproteome Profiling of SH-SY5y neuroblastoma cells treated with anesthetics: sevoflurane and isoflurane affect the phosphorylation of proteins involved in cytoskeletal regulation. PLoS One 11:e0162214. https://doi.org/10.1371/journal.pone.0162214
Liu Y, Gorospe M, Yang C, Holbrook NJ (1995) Role of mitogen-activated protein kinase phosphatase during the cellular response to genotoxic stress. Inhibition of c-Jun N-terminal kinase activity and AP-1-dependent gene activation. J Biol Chem 270:8377–8380
Makaryus R, Lee H, Feng T, Park JH et al (2015) Brain maturation in neonatal rodents is impeded by sevoflurane anesthesia. Anesthesiology 123:557–568. https://doi.org/10.1097/ALN.0000000000000762
Marchese FP, Raimondi I, Huarte M (2017) The multidimensional mechanisms of long noncoding RNA function. Genome Biol 18:206. https://doi.org/10.1186/s13059-017-1348-2
Marques-Rocha JL, Samblas M, Milagro FI, Bressan J et al (2015) Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J 29:3595–3611. https://doi.org/10.1096/fj.14-260323
Meyer KD, Patil DP, Zhou J, Zinoviev A et al (2015) 5 UTR m(6)A promotes cap-independent translation. Cell 163:999–1010. https://doi.org/10.1016/j.cell.2015.10.012
Pape K, Tamouza R, Leboyer M, Zipp F (2019) Immunoneuropsychiatry - novel perspectives on brain disorders. Nat Rev Neurol 15:317–328. https://doi.org/10.1038/s41582-019-0174-4
Raman M, Chen W, Cobb MH (2007) Differential regulation and properties of MAPKs. Oncogene 26:3100–3112
Saika R, Sakuma H, Noto D, Yamaguchi S et al (2017) MicroRNA-101a regulates microglial morphology and inflammation. 14:109. https://doi.org/10.1186/s12974-017-0884-8
Satomoto M, Satoh Y, Terui K, Miyao H et al (2009) Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 110:628–637. https://doi.org/10.1097/ALN.0b013e3181974fa2
Seger R, Krebs EG (1995) The MAPK signaling cascade. FASEB J 9:726–735
Shen Q, Zheng J, Wang X, Hu W et al (2020) LncRNA SNHG5 regulates cell apoptosis and inflammation by miR-132/PTEN axis in COPD. Biomed Pharmacother 126:110016. https://doi.org/10.1016/j.biopha.2020.110016
Shen X, Dong Y, Xu Z, Wang H et al (2013) Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology 118:502–515. https://doi.org/10.1097/ALN.0b013e3182834d77
Stratmann G, Lee J, Sall JW, Lee BH et al (2014) Effect of general anesthesia in infancy on long-term recognition memory in humans and rats. Neuropsychopharmacology 39:2275–2287. https://doi.org/10.1038/npp.2014.134
Sun H, Charles CH, Lau LF, Tonks NK (1993) MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell 75:487–493
Tao G, Zhang J, Zhang L, Dong Y et al (2014) Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3beta activation in young mice. Anesthesiology 121:510–527. https://doi.org/10.1097/ALN.0000000000000278
Vutskits L, Xie Z (2016) Lasting impact of general anaesthesia on the brain: mechanisms and relevance. Nat Rev Neurosci 17:705–717. https://doi.org/10.1038/nrn.2016.128
Weiser TG, Regenbogen SE, Thompson KD, Haynes AB et al (2008) An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet 372:139–144. https://doi.org/10.1016/S0140-6736(08)60878-8
Wu GS (2007) Role of mitogen-activated protein kinase phosphatases (MKPs) in cancer. Cancer Metastasis Rev 26:579–585
Xu G, Lu H, Dong Y, Shapoval D et al (2017) Coenzyme Q10 reduces sevoflurane-induced cognitive deficiency in young mice. Br J Anaesth 119:481–491. https://doi.org/10.1093/bja/aex071
Yang M, Lian N, Yu Y, Wang Y et al (2020) Coenzyme Q10 alleviates sevofluraneinduced neuroinflammation by regulating the levels of apolipoprotein E and phosphorylated tau protein in mouse hippocampal neurons. Mol Med Rep 22:445–453. https://doi.org/10.3892/mmr.2020.11131
Yao RW, Wang Y, Chen LL (2019) Cellular functions of long noncoding RNAs. Nat Cell Biol 21:542–551. https://doi.org/10.1038/s41556-019-0311-8
Zhang J, Dong Y, Lining H, Xu X et al (2020) Interaction of Tau, IL-6 and mitochondria on synapse and cognition following sevoflurane anesthesia in young mice. Brain Behav Immun Health 8:100133. https://doi.org/10.1016/j.bbih.2020.100133
Zhang L, Xue Z, Liu Q, Liu Y et al (2019a) Disrupted folate metabolism with anesthesia leads to myelination deficits mediated by epigenetic regulation of ERMN. EBioMedicine 43:473–486. https://doi.org/10.1016/j.ebiom.2019.04.048
Zhang L, Xue Z, Yan J, Wang J et al (2019b) LncRNA Riken-201 and Riken-203 modulates neural development by regulating the Sox6 through sequestering miRNAs. Cell Prolif 52:e12573. https://doi.org/10.1111/cpr.12573
Zhang L, Yan J, Liu Q, Xie Z et al (2019c) LncRNA Rik-203 contributes to anesthesia neurotoxicity via microRNA-101a-3p and GSK-3beta-mediated neural differentiation[J]. Sci Rep 9(1):6822. https://doi.org/10.1038/s41598-019-42991-4
Zhang P, Cao L, Zhou R, Yang X et al (2019d) The lncRNA Neat1 promotes activation of inflammasomes in macrophages. Nat Commun 10:1495. https://doi.org/10.1038/s41467-019-09482-6
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 235:957–965. https://doi.org/10.1002/jcp.29011
Zheng H, Dong Y, Xu Z, Crosby G et al (2013) Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice. Anesthesiology 118:516–526. https://doi.org/10.1097/ALN.0b013e3182834d5d
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The present study was supported by the National Natural Science Foundation of China (Grant No. 81970994, Grant No. 81801047, Grant No.82101281, Grant No.82171195).
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Hou, Q., Li, S., Zhang, B. et al. LncRNA Riken Attenuated Sevoflurane-Induced Neuroinflammation by Regulating the MicroRNA-101a/MKP-1/JNK Pathway. Neurotox Res 40, 186–197 (2022). https://doi.org/10.1007/s12640-021-00443-w
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DOI: https://doi.org/10.1007/s12640-021-00443-w