Involvement of microRNA-138-5p in cardiac surgery-induced postoperative cognitive dysfunction
Abstract
Background: Despite being one of the main concerns in cardiac surgery, the molecular basis and regulatory mechanisms of postoperative cognitive dysfunction (POCD) are still unclear. In this study, we demonstrate the critical role of miR-138-5p in POCD in mice.
Methods: We first established an animal model for POCD caused by cardiac surgery. We then used quantitative reverse transcription polymerase chain reaction to examine the expression levels of miR-138-5p and its target mRNAs. The protein level of sirtuin 1 (SIRT1) was determined using Western blot assays. To assess the mice’s recognition abilities, we performed the Morris water maze (MWM) test. Enzyme-linked immunosorbent assays were used to evaluate the expression levels of hippocampal inflammatory cytokines. Finally, we used a luciferase assay to confirm that miR-138-5p directly targeted the mRNA of SIRT1.
Results: MiR-138-5p was upregulated in the hippocampus of mice following cardiac surgery. Inhibiting miR-138-5p reduced the occurrence of POCD and the hippocampus inflammation in the mice. MiR-138-5p targeted the mRNA of SIRT1, thereby suppressing its expression in the hippocampus of mice following cardiac surgery.
Conclusion: Our findings suggest that miR-138-5p contributes to cardiac surgery-induced POCD by directly targeting and suppressing the expression of SIRT1 in the hippocampus.
Downloads
References
de Tournay-Jette E, Dupuis G, Bherer L, Deschamps A, Cartier R, Denault A. The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2011; 25(1): 95–104. doi: 10.1053/j.jvca.2010.03.019
Abbott MW, Gregson RA. Cognitive dysfunction in the prediction of relapse in alcoholics. J Stud Alcohol 1981; 42(3): 230–43. doi: 10.15288/jsa.1981.42.230
Grubb NR, Simpson C, Sherwood RA, Abraha HD, Cobbe SM, O’Carroll RE, et al. Prediction of cognitive dysfunction after resuscitation from out-of-hospital cardiac arrest using serum neuron-specific enolase and protein S-100. Heart 2007; 93(10): 1268–73. doi: 10.1136/hrt.2006.091314
Hong SW, Shim JK, Choi YS, Kim DH, Chang BC, Kwak YL. Prediction of cognitive dysfunction and patients’ outcome following valvular heart surgery and the role of cerebral oximetry. Eur J Cardiothorac Surg 2008; 33(4): 560–5. doi: 10.1016/j.ejcts.2008.01.012
Medrzycka-Dabrowska WA, Czyz-Szybenbejl K, Kwiecien-Jagus K, Lewandowska K. Prediction of cognitive dysfunction after resuscitation – a systematic review. Postepy Kardiol Interwencyjnej 2018; 14(3): 225–32. doi: 10.5114/aic.2018.78324
Park JH, Park H, Sohn SW, Kim S, Park KW. Memory performance on the story recall test and prediction of cognitive dysfunction progression in mild cognitive impairment and Alzheimer’s dementia. Geriatr Gerontol Int 2017; 17(10): 1603–9. doi: 10.1111/ggi.12940
Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991; 41(5): 685–91. doi: 10.1212/WNL.41.5.685
Sussman ES, Kellner CP, Mergeche JL, Bruce SS, McDowell MM, Heyer EJ, et al. Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy. J Neurosurg 2014; 121(3): 593–8. doi: 10.3171/2014.5.JNS131736
Salazar JD, Wityk RJ, Grega MA, Borowicz LM, Doty JR, Petrofski JA, et al. Stroke after cardiac surgery: Short- and long-term outcomes. Ann Thorac Surg 2001; 72(4): 1195–201. doi: 10.1016/S0003-4975(01)02929-0
Bhamidipati D, Goldhammer JE, Sperling MR, Torjman MC, McCarey MM, Whellan DJ. Cognitive outcomes after coronary artery bypass grafting. J Cardiothorac Vasc Anesth 2017; 31(2): 707–18. doi: 10.1053/j.jvca.2016.09.028
Hong SW, Shim JK, Choi YS, Kim DH, Chang BC, Kwak YL. Prediction of cognitive dysfunction and patients’ outcome following valvular heart surgery and the role of cerebral oximetry. Eur J Cardiothorac Surg 2008; 33(4): 560–5. doi: 10.1016/j.ejcts.2008.01.012
Yu Y, Zhang KY, Zhang L, Zong HT, Meng LZ, Han RQ. Cerebral near-infrared spectroscopy (NIRS) for perioperative monitoring of brain oxygenation in children and adults. Cochrane Database Syst Rev 2018; 1(1): CD010947. doi: 10.1002/14651858.CD010947.pub2
Serraino GF, Murphy GJ. Effects of cerebral near-infrared spectroscopy on the outcome of patients undergoing cardiac surgery: a systematic review of randomised trials. BMJ Open 2017; 7(9): e016613. doi: 10.1136/bmjopen-2017-016613
Skvarc DR, Berk M, Byrne LK, Dean OM, Dodd S, Lewis M, et al. Post-operative cognitive dysfunction: an exploration of the inflammatory hypothesis and novel therapies. Neurosci Biobehav Rev 2018; 84: 116–33. doi: 10.1016/j.neubiorev.2017.11.011
Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac-surgery. Ann Thorac Surg 1995; 59(5): 1289–95. doi: 10.1016/0003-4975(95)00106-U
Berger M, Terrando N, Smith SK, Browndyke JN, Newman MF, Mathew JP. Neurocognitive function after cardiac surgery from phenotypes to mechanisms. Anesthesiology 2018; 129(4): 829–51. doi: 10.1097/ALN.0000000000002194
Ferrante M, Conti GO. Environment and neurodegenerative diseases: an update on miRNA role. Microrna 2017; 6(3): 157–65. doi: 10.2174/2211536606666170811151503
Yu C, Wang M, Li ZP, Xiao J, Peng F, Guo XJ, et al. MicroRNA-138-5p regulates pancreatic cancer cell growth through targeting FOXC1. Cell Oncol 2015; 38(3): 173–81. doi: 10.1007/s13402-014-0200-x
Zhao C, Ling X, Li X, Hou X, Zhao D. MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1. Breast Cancer 2019; 26(6): 817–25. doi: 10.1007/s12282-019-00989-w
Schoemaker RG, Smits JFM. Behavioral-changes following chronic myocardial-infarction in rats. Physiol Behav 1994; 56(3): 585–9. doi: 10.1016/0031-9384(94)90305-0
Androsova G, Krause R, Winterer G, Schneider R. Biomarkers of postoperative delirium and cognitive dysfunction. Front Aging Neurosci 2015; 7: 112. doi: 10.3389/fnagi.2015.00112
Rasmussen LS, Larsen K, Houx P, Skovgaard LT, Hanning CD, Moller JT, et al. The assessment of postoperative cognitive function. Acta Anaesthesiol Scand 2001; 45(3): 275–89. doi: 10.1034/j.1399-6576.2001.045003275.x
Al Hazzouri AZ, Haan MN, Kalbfleisch JD, Galea S, Lisabeth LD, Aiello AE. Life course socioeconomic position and incidence of dementia and cognitive impairment without dementia in older Mexican Americans: results from the Sacramento Area Latino study on aging. Am J Epidemiol 2011; 173: S244. doi: 10.1093/aje/kwq483
Ritchie K. Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors (vol 341, c3885, 2010). BMJ 2010; 341: c3885. doi: 10.1136/bmj.c3885
Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery. Ann Thorac Surg 1995; 59(5): 1289–95. doi: 10.1016/0003-4975(95)00106-U
Patel N, Minhas JS, Chung EM. Risk factors associated with cognitive decline after cardiac surgery: a systematic review. Cardiovasc Psychiatry Neurol 2015; 2015: 370612. doi: 10.1155/2015/370612
Derry S, Moore RA. Single dose oral celecoxib for acute postoperative pain in adults. Cochrane Database Syst Rev 2013; 2013(10): CD004233. doi: 10.1002/14651858.CD010107.pub2
Dhanda S, Kaur S, Sandhir R. Preventive effect of N-acetyl-L-cysteine on oxidative stress and cognitive impairment in hepatic encephalopathy following bile duct ligation. Free Radic Biol Med 2013; 56: 204–15. doi: 10.1016/j.freeradbiomed.2012.09.017
Mohr AM, Mott JL. Overview of MicroRNA biology. Semin Liver Dis 2015; 35(1): 3–11. doi: 10.1055/s-0034-1397344
Acunzo M, Croce CM. MicroRNA in cancer and cachexia – a mini-review. J Infect Dis 2015; 212: S74–7. doi: 10.1093/infdis/jiv197
Wei C, Luo T, Zou S, Zhou X, Shen W, Ji X, et al. Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction. Oncotarget 2017; 8(34): 55901–14. doi: 10.18632/oncotarget.18362
Wang Y, Huang A, Gan L, Bao Y, Zhu W, Hu Y, et al. Screening of potential genes and transcription factors of postoperative cognitive dysfunction via bioinformatics methods. Med Sci Monit 2018; 24: 503–10. doi: 10.12659/MSM.907445
Liu Q, Hou A, Zhang Y, Guo Y, Li J, Yao Y, et al. MiR-190a potentially ameliorates postoperative cognitive dysfunction by regulating Tiam1. BMC Genomics 2019; 20(1): 670. doi: 10.1186/s12864-019-6035-0
Lu XH, Lv SG, Mi Y, Wang L, Wang GS. Neuroprotective effect of miR-665 against sevoflurane anesthesia-induced cognitive dysfunction in rats through PI3K/Akt signaling pathway by targeting insulin-like growth factor 2. Am J Transl Res 2017; 9(3): 1344–56.
Qu Y, Zhang QD, Cai XB, Li F, Ma ZZ, Xu MY, et al. Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med 2017; 21(10): 2491–502. doi: 10.1111/jcmm.13170
Zhao L, Yu H, Yi S, Peng X, Su P, Xiao Z, et al. The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer. Oncotarget 2016; 7(29): 45370–84. doi: 10.18632/oncotarget.9659
Yang R, Liu MH, Liang HW, Guo SH, Guo X, Yuan M, et al. miR-138-5p contributes to cell proliferation and invasion by targeting Survivin in bladder cancer cells. Mol Cancer 2016; 15: 82. doi: 10.1186/s12943-016-0569-4
Kumar S, Kim YR, Vikram A, Naqvi A, Li QX, Kassan M, et al. Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction. Proc Natl Acad Sci U S A 2017; 114(7): 1714–9. doi: 10.1073/pnas.1614112114
Chu HY, Jiang S, Liu QM, Ma YY, Zhu XX, Liang MR, et al. Sirtuin1 protects against systemic sclerosis-related pulmonary fibrosis by decreasing proinflammatory and profibrotic processes. Am J Respir Cell Mol Biol 2018; 58(1): 28–39. doi: 10.1165/rcmb.2016-0192OC
Yang H, Bi Y, Xue L, Wang J, Lu Y, Zhang Z, et al. Multifaceted modulation of SIRT1 in cancer and inflammation. Crit Rev Oncog 2015; 20(1–2): 49–64. doi: 10.1615/CritRevOncog.2014012374
Qiang L, Sample A, Liu H, Wu X, He YY. Epidermal SIRT1 regulates inflammation, cell migration, and wound healing. Sci Rep 2017; 7(1): 14110. doi: 10.1038/s41598-017-14371-3
Herskovits AZ, Guarente L. SIRT1 in neurodevelopment and brain senescence. Neuron 2014; 81(3): 471–83. doi: 10.1016/j.neuron.2014.01.028
Yan J, Luo A, Gao J, Tang X, Zhao Y, Zhou B, et al. The role of SIRT1 in neuroinflammation and cognitive dysfunction in aged rats after anesthesia and surgery. Am J Transl Res 2019; 11(3): 1555–68.
Yan WJ, Wang DB, Ren DQ, Wang LK, Hu ZY, Ma YB, et al. AMPK1 overexpression improves postoperative cognitive dysfunction in aged rats through AMPK-Sirt1 and autophagy signaling. J Cell Biochem 2019; 120(7): 11633–41. doi: 10.1002/jcb.28443
Copyright (c) 2023 Pavan Bandhu, Kartik Das
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain full copyright to their individual works, and publishing rights without restrictions.
In accordance with the Budapest Open Access Initiative, articles published in STEMedicine are freely available "on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited."
Except where otherwise noted, all content on this website is licensed under a Creative Commons Attribution 4.0 License. This license allows for commercial and non-commercial redistribution as well as modifications of the work as long as attribution is given to the authors and STEMedicine as the original publication source, and a link to the article on the STEMedicine website is provided.
