Advertisement

Up-regulation of miR-106a targets LIMK1 and contributes to cognitive impairment induced by isoflurane anesthesia in mice

  • Ning Zhang
  • Weiguang Ye
  • Tianlong Wang
  • Hui Wen
  • Lan YaoEmail author
Research Article
  • 7 Downloads

Abstract

Background

Postoperative cognitive dysfunction (POCD) had a great relationship with anesthesia during surgery, and miRNAs have been found involved in anesthesia-induced cognitive impairment.

Objective

To explore the role and potential mechanism of miR-106a in isoflurane anesthesia-induced cognitive impairment.

Methods

Adult male mice were treated with isoflurane anesthesia; Morris water maze tests and fear conditioning tests were performed; and expression levels of miR-106a and LIMK1 were determined by quantitative real-time PCR (qRT-PCR) and western blot. Dual luciferase reporter assay was used to determine the binding of miR-106a and 3’UTR of LIMK1. To verify the role of miR-106a, antagomir of miR-106a were intrahippocampally injected. Finally, expression of BCL2 apoptosis regulator (Bcl-2), LIM domain kinase 1 (LIMK1), BCL2-associated X, apoptosis regulator (Bax) and cleaved caspase3 was determined by western blot.

Results

In isoflurane anesthesia-treated group (IS), the percentage of target quadrant dwell time was significantly lower and the escape latency was significantly higher than in the control group (sham), and the freezing behavior of IS was significantly less in contextual fear conditioning tests. Expression levels of miR-106a were increased and those of LIMK1 were decreased in response to IS. Dual luciferase reporter assay showed that miR-106a could bind with the 3’UTR of LIMK1. Decreased expression levels of miR-106a improved the cognitive impairment of the mice treated with isoflurane. Intrahippocampally injected antagomir of miR-106a also increased LIMK1 and Bcl-2 levels, decreased the BAX and cleaved caspase3 expression levels in the mice treated with isoflurane.

Conclusion

Decrease of LIMK1 expression by miR-106a played an important role in isoflurane anesthesia-induced cognitive impairment.

Keywords

miR-106a LIMK1 Isoflurane anesthesia Cognitive impairment 

Notes

Author contributions

NZ and LY conceived and designed the experiments, WGY analyzed and interpreted the results of the experiments, TLW and HW performed the experiments.

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests, and all authors should confirm its accuracy.

Ethics approval and consent to participate

The animal use peotocol listed below has been reviewde and approved by the Animal Ethical and Welfaer Committee.

References

  1. Cao Y, Li Z, Ma L, Ni C, Li L, Yang N, Shi C, Guo X (2018) Isoflurane-induced postoperative cognitive dysfunction is mediated by hypoxia-inducible factor-1α-dependent neuroinflammation in aged rats. Mol Med Rep 17:7730–7736PubMedPubMedCentralGoogle Scholar
  2. Chavan SS, Huerta PT, Robbiati S, Valdes-Ferrer SI, Ochani M, Dancho M, Frankfurt M, Volpe BT, Tracey KJ, Diamond B (2012) HMGB1 mediates cognitive impairment in sepsis survivors. Mol Med (Camb Mass) 18:930–937CrossRefGoogle Scholar
  3. Chen Y, Huang T, Yang X, Liu C, Li P, Wang Z, Zhi S (2018) MicroRNA-106a regulates the proliferation and invasion of human osteosarcoma cells by targeting VNN2. Oncol Rep 40:2251–2259PubMedGoogle Scholar
  4. Cong J, Wang C, Pu D, Liu J, Hu G, Gao C, Wu J (2014) Expression of early growth response 1 affects miR-106a/signal transducer and activator of transcription 3 regulating cognitive impairment in ovariectomized mice. Menopause 21:1143–1150CrossRefGoogle Scholar
  5. Dong Q, Ji Y-S, Cai C, Chen Z-Y (2012) LIM kinase 1 (LIMK1) interacts with tropomyosin-related kinase B (TrkB) and Mediates brain-derived neurotrophic factor (BDNF)-induced axonal elongation. J Biol Chem 287:41720–41731CrossRefGoogle Scholar
  6. Fang Y, Shen H, Li H, Cao Y, Qin R, Long L, Zhu X, Xie C, Xu W (2013) miR-106a confers cisplatin resistance by regulating PTEN/Akt pathway in gastric cancer cells. Acta Biochim Biophys Sin 45:963–972CrossRefGoogle Scholar
  7. Geng Y-j, Wu Q-h, Zhang R-q (2017) Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial. J Clin Anesth 38:165–171CrossRefGoogle Scholar
  8. Goto G, Hori Y, Ishikawa M, Tanaka S, Sakamoto A (2014) Changes in the gene expression levels of microRNAs in the rat hippocampus by sevoflurane and propofol anesthesia. Mol Med Rep 9:1715–1722CrossRefGoogle Scholar
  9. Hackl M, Brunner S, Fortschegger K, Schreiner C, Micutkova L, Muck C, Laschober GT, Lepperdinger G, Sampson N, Berger P et al (2010) miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging. Aging Cell 9:291–296CrossRefGoogle Scholar
  10. Hu B, Cai H, Zheng R, Yang S, Zhou Z, Tu J (2017) Long non-coding RNA 657 suppresses hepatocellular carcinoma cell growth by acting as a molecular sponge of miR-106a-5p to regulate PTEN expression. Int J Biochem Cell Biol 92:34–42CrossRefGoogle Scholar
  11. Issler O, Chen A (2015) Determining the role of microRNAs in psychiatric disorders. Nat Rev Neurosci 16:201–212CrossRefGoogle Scholar
  12. Knafo S, Sánchez-Puelles C, Palomer E, Delgado I, Draffin JE, Mingo J, Wahle T, Kaleka K, Mou L, Pereda-Perez I et al (2016) PTEN recruitment controls synaptic and cognitive function in Alzheimer's models. Nat Neurosci 19:443CrossRefGoogle Scholar
  13. Kong F, Chen S, Cheng Y, Ma L, Lu H, Zhang H, Hu W (2013) Minocycline attenuates cognitive impairment induced by isoflurane anesthesia in aged rats. PLoS ONE 8:e61385–e61385CrossRefGoogle Scholar
  14. Li GF, Li ZB, Zhuang SJ, Li GC (2018) Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway. Neurosci Lett 675:152–159CrossRefGoogle Scholar
  15. Liu A, Zhou Z, Dang R, Zhu Y, Qi J, He G, Leung C, Pak D, Jia Z, Xie W (2016) Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization. J Cell Biol 212:449–463CrossRefGoogle Scholar
  16. Liu L, Zhao Z, Lu L, Liu J, Wu X, Sun J, Wei Y, Dong J (2018a) The role of HMGB1 in neuroinflammation and tissue repair: A potential therapeutic target for depression? Tradit Med Mod Med 01:85–93CrossRefGoogle Scholar
  17. Liu R, Luo Q, You W, Jin M (2018b) MicroRNA-106 attenuates hyperglycemia-induced vascular endothelial cell dysfunction by targeting HMGB1. Gene 677:142–148CrossRefGoogle Scholar
  18. Lu Y, Xu X, Dong R, Sun L, Chen L, Zhang Z, Peng M (2019) MicroRNA-181b-5p attenuates early postoperative cognitive dysfunction by suppressing hippocampal neuroinflammation in mice. Cytokine 120:41–53CrossRefGoogle Scholar
  19. Pan Y, Zhuang Y, Zheng J, Pei D (2016) MiR-106a: Promising biomarker for cancer. Bioorg Med Chem Lett 26:5373–5377CrossRefGoogle Scholar
  20. Piscopo P, Lacorte E, Feligioni M, Mayer F, Crestini A, Piccolo L, Bacigalupo I, Filareti M, Ficulle E, Confaloni A et al (2019) MicroRNAs and mild cognitive impairment: a systematic review. Ageing Res Rev 50:131–141CrossRefGoogle Scholar
  21. Qiao Y, Feng H, Zhao T, Yan H, Zhang H, Zhao X (2015) Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation. BMC Anesthesiology 15:154–154CrossRefGoogle Scholar
  22. Rosso S, Bollati F, Bisbal M, Peretti D, Sumi T, Nakamura T, Quiroga S, Ferreira A, Cáceres A (2004) LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. Mol Biol Cell 15:3433–3449CrossRefGoogle Scholar
  23. Rundshagen I (2014) Postoperative cognitive dysfunction. Deutsches Arzteblatt Int 111:119–125Google Scholar
  24. Shi B, Ma C, Liu G, Guo Y (2019) MiR-106a directly targets LIMK1 to inhibit proliferation and EMT of oral carcinoma cells. Cell Mol Biol Lett 24:1CrossRefGoogle Scholar
  25. Shoji H, Takao K, Hattori S, Miyakawa T (2014) Contextual and cued fear conditioning test using a video analyzing system in mice. J Visualized Exp.  https://doi.org/10.3791/50871 CrossRefGoogle Scholar
  26. Su B, Su J, Zeng Y, Liu F, Xia H, Ma Y-H, Zhou Z-G, Zhang S, Yang B-M, Wu Y-H et al (2016) Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and proliferation by downregulation of LIMK1 in gastric cancer. Oncotarget 7:10498–10512PubMedPubMedCentralGoogle Scholar
  27. Sun W-C, Pei L (2016) rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes. J Neurochem 138:233–242CrossRefGoogle Scholar
  28. Sun E, Shi Y (2015) MicroRNAs: Small molecules with big roles in neurodevelopment and diseases. Exp Neurol 268:46–53CrossRefGoogle Scholar
  29. Todorovski Z, Asrar S, Liu J, Saw NMN, Joshi K, Cortez MA, Snead OC, Xie W, Jia Z (2015) LIMK1 regulates long-term memory and synaptic plasticity via the transcriptional factor CREB. Mol Cell Biol 35:1316–1328CrossRefGoogle Scholar
  30. Wang W, Wang Y, Wu H, Lei L, Xu S, Shen X, Guo X, Shen R, Xia X, Liu Y et al (2014) Postoperative cognitive dysfunction: current developments in mechanism and prevention. Med Sci Monit 20:1908–1912CrossRefGoogle Scholar
  31. Wang H, Ban W, Wang T, Li Z, Dang X (2017) miR-20b/106a modulate Ngn2 gene expression during neural differentiation of human umbilical cord mesenchymal stem cells. Neuro Report 28:1225–1231Google Scholar
  32. Wang L, Zheng M, Wu S, Niu Z (2018) MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by targeting MDM2. Mol Med Rep 17:4229–4236PubMedPubMedCentralGoogle Scholar
  33. Ward CG, Eckenhoff RG (2016) Neurocognitive adverse effects of anesthesia in adults and children: gaps in knowledge. Drug Saf 39:613–626CrossRefGoogle Scholar
  34. Wei C, Luo T, Zou S, Zhou X, Shen W, Ji X, Li Q, Wu A (2017) Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction. Oncotarget 8:55901–55914PubMedPubMedCentralGoogle Scholar
  35. Yu Y, Zhang P, Yan J, Sun Y, Wu X, Xi S, Zhang L, Sun Y, Hu R, Jiang H (2016) Sevoflurane induces cognitive impairments via the MiR-27b/LIMK1-signaling pathway in developing rats. Inhalation Toxicol 28:731–738CrossRefGoogle Scholar
  36. Yuan R, Wang G, Xu Z, Zhao H, Chen H, Han Y, Wang B, Zhou J, Hu H, Guo Z (2016) Up-regulated circulating miR-106a by DNA methylation promised a potential diagnostic and prognostic marker for gastric cancer. Anticancer Agents Med Chem 16:1093–1100CrossRefGoogle Scholar
  37. Zhang Q, Li Y, Bao Y, Yin C, Xin X, Guo Y, Gao F, Huo S, Wang X, Wang Q (2018) Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin mediated hippocampal neuroapoptosis in aged rats. BMC Anesthesiol 18:42CrossRefGoogle Scholar
  38. Zhao Y, Wang J, Du J, Li B, Gou X, Liu J, Hou L, Sang H, Deng B (2018) TAT-Ngn2 enhances cognitive function recovery and regulates caspase-dependent and mitochondrial apoptotic pathways after experimental stroke. Front Cell Neurosci 12:475.  https://doi.org/10.3389/fncel.2018.00475 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Zuo C-L, Wang C-M, Liu J, Shen T, Zhou J-P, Hao X-R, Pan Y-Z, Liu H-C, Lian Q-Q, Lin H (2018) Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on cognitive impairment. CNS Neurosci Ther 24:212–221CrossRefGoogle Scholar

Copyright information

© The Genetics Society of Korea 2020

Authors and Affiliations

  • Ning Zhang
    • 1
  • Weiguang Ye
    • 2
  • Tianlong Wang
    • 2
  • Hui Wen
    • 1
  • Lan Yao
    • 1
    Email author
  1. 1.Department of AnesthesiaPeking University International HospitalBeijingChina
  2. 2.Department of AnesthesiaXuanwu Hospital of Capital Medical UniversityBeijingChina

Personalised recommendations