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miR-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation

Chen, Yan, Sun, Jing-xian, Chen, Wan-kun, Wu, Gen-cheng, Wang, Yan-qing, Zhu, Ke-ying, Wang, Jun·2019·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-019-0061-xPMC PMC6799846
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Abstract

Activation of microglia and the subsequently elevated inflammatory cytokine release in the brain during surgery predispose individuals to cognitive dysfunction, also known as postoperative cognitive dysfunction (POCD). miR-124 is one of the most abundant microRNAs in the brain that regulates microglial function. Elucidating the role of miR-124 in microglial activation in the context of surgery may therefore promote understanding of as well as therapeutic development for post-surgical disorders involving microglial activation. The downstream targets of miR-124 were investigated using bioinformatic screening and dual-luciferase reporter assay validation, and vesicle-associated membrane protein 3 (VAMP3) was identified as a potential target. The kinetics of miR-124/VAMP3 expression was first examined in vitro in microglial cells (primary microglia and BV2 microglial cells) following lipopolysaccharide (LPS) stimulation. LPS induced a time-dependent decrease of miR-124 and upregulated the expression of VAMP3. Manipulating miR-124/VAMP3 expression by using miR-124 mimics or VAMP3-specific siRNA in LPS-stimulated BV2 microglial cells inhibited BV2 microglial activation-associated inflammatory cytokine release. To further examine the role of miR-124/VAMP3 in a surgical setting, we employed a rat surgical trauma model. Significant microglial activation and altered miR-124/VAMP3 expression were observed following surgical trauma. We also altered miR-124/VAMP3 expression in the rat surgical trauma model by administration of exogenous miR-124 and by using electroacupuncture, which is a clinically applicable treatment that modulates microglial function and minimizes postoperative disorders. We determined that electroacupuncture treatment specifically increases the expression of miR-124 in the hypothalamus and hippocampus. Increased miR-124 expression with a concomitant decrease in VAMP3 expression resulted in decreased inflammatory cytokine release related to microglial activation post-surgery. Our study indicates that miR-124/VAMP3 is involved in surgery-induced microglial activation and that targeting miR-124/VAMP3 could be a potential therapeutic strategy for postoperative disorders involving microglial activation.

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  1. Dimopoulou, I. et al. Tumour necrosis factor-alpha (TNFalpha) and interleukin-10 are crucial mediators in post-operative systemic inflammatory response and determine the occurrence of complications after major abdominal surgery. Cytokine 37, 55–61 (2007). · DOI
  2. Berger, M. et al. Best practices for postoperative brain health: recommendations from the Fifth International Perioperative Neurotoxicity Working Group. Anesth. Analg. 127, 1406–1413 (2018). · DOI
  3. Laalou, F.-Z., Jochum, D. & Pain, L. [Postoperative cognitive dysfunction (POCD): strategy of prevention, assessment and management]. Ann. Fr. Anesth. Reanim. 30, e49–e53 (2011). · DOI
  4. Tsai, T. L., Sands, L. P. & Leung, J. M. An update on postoperative cognitive dysfunction. Adv. Anesth. 28, 269–284 (2010). · DOI
  5. Zhang, X. et al. Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and neuronal apoptosis. J. Neuroinflammation 13, 127 (2016). · DOI
  6. Feng, X. et al. Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice. JCI Insight 2, e91229 (2017). · DOI
  7. Hovens, I. B. et al. Postoperative cognitive dysfunction: Involvement of neuroinflammation and neuronal functioning. Brain Behav. Immun. 38, 202–210 (2014). · DOI
  8. Cibelli, M. et al. Role of interleukin-1β in postoperative cognitive dysfunction. Ann. Neurol. 68, 360–368 (2010). · DOI
  9. Colonna, M. & Butovsky, O. Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 35, 441–468 (2017). · DOI · Paper page
  10. Wang, W.-Y., Tan, M.-S., Yu, J.-T. & Tan, L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann. Transl. Med. 3, 136 (2015).
  11. Lyon, D. E. et al. Relationship of systemic cytokine concentrations to cognitive function over two years in women with early stage breast cancer. J. Neuroimmunol. 301, 74–82 (2016). · DOI
  12. Terrando, N. et al. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc. Natl Acad. Sci. USA 107, 20518–20522 (2010). · DOI
  13. Wan, Y. et al. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 106, 436–443 (2007). · DOI
  14. Hovens, I. B. et al. Surgery-induced behavioral changes in aged rats. Exp. Gerontol. 48, 1204–1211 (2013). · DOI
  15. Alazawi, W., Pirmadjid, N., Lahiri, R. & Bhattacharya, S. Inflammatory and immune responses to surgery and their clinical impact. Ann. Surg. 264, 73–80 (2016). · DOI
  16. Guedes, J., Cardoso, A. L. C. & Pedroso de Lima, M. C. Involvement of microRNA in microglia-mediated immune response. Clin. Dev. Immunol. 2013, 186872 (2013). · DOI · Paper page
  17. Sun, Y. et al. MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines. Cell Res. 23, 1270–1283 (2013). · DOI · Paper page
  18. Wang, J. et al. Electroacupuncture downregulates TLR2/4 and pro-inflammatory cytokine expression after surgical trauma stress without adrenal glands involvement. Brain Res. Bull. 80, 89–94 (2009). · DOI
  19. Grech, D. et al. Intraoperative low-frequency electroacupuncture under general anesthesia improves postoperative recovery in a randomized trial. J. Acupunct. Meridian Stud. 9, 234–241 (2016). · DOI
  20. Zhu, K. et al. Electroacupuncture promotes remyelination after cuprizone treatment by enhancing myelin debris clearance. Front. Neurosci. 10, 613 (2016).
  21. Zhang, H.-H. et al. Protective effects of electroacupuncture on cardiac function in rats subjected to thoracic surgery trauma. Brain Res. Bull. 89, 71–78 (2012). · DOI
  22. Ng, S. S. M. et al. Electroacupuncture reduces duration of postoperative ileus after laparoscopic surgery for colorectal cancer. Gastroenterology 144, 307–313.e1 (2013). · DOI
  23. Wang, K. et al. The effects of electroacupuncture on TH1/TH2 cytokine mRNA expression and mitogen-activated protein kinase signaling pathways in the splenic T cells of traumatized rats. Anesth. Analg. 109, 1666–1673 (2009). · DOI
  24. Wang, J. et al. Beta-adrenoceptor mediated surgery-induced production of pro-inflammatory cytokines in rat microglia cells. J. Neuroimmunol. 223, 77–83 (2010). · DOI
  25. Zhu, K. et al. Repurposing of omeprazole for oligodendrocyte differentiation and remyelination. Brain Res. 1710, 33–42 (2019). · DOI
  26. Goldman, N. et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat. Neurosci. 13, 883–888 (2010). · DOI
  27. Torres-Rosas, R. et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat. Med. 20, 291–295 (2014). · DOI
  28. Boddul, S. V., Meng, J., Dolly, J. O. & Wang, J. SNAP-23 and VAMP-3 contribute to the release of IL-6 and TNFα from a human synovial sarcoma cell line. FEBS J. 281, 750–765 (2014). · DOI
  29. Yang, Z. et al. Activation of integrin β1 mediates the increased malignant potential of ovarian cancer cells exerted by inflammatory cytokines. Anticancer Agents Med. Chem. 14, 955–962 (2014). · DOI
  30. Dai, E. et al. Serp-1, a viral anti-inflammatory serpin, regulates cellular serine proteinase and serpin responses to vascular injury. J. Biol. Chem. 278, 18563–18572 (2003). · DOI
  31. Hunt, S., Jones, A. V., Hinsley, E. E., Whawell, S. A. & Lambert, D. W. MicroRNA-124 suppresses oral squamous cell carcinoma motility by targeting ITGB1. FEBS Lett. 585, 187–192 (2011). · DOI
  32. Nasu-Tada, K., Koizumi, S. & Inoue, K. Involvement of β1 integrin in microglial chemotaxis and proliferation on fibronectin: different regulations by ADP through PKA. Glia 52, 98–107 (2005). · DOI
  33. Nutile-McMenemy, N., Elfenbein, A. & Deleo, J. A. Minocycline decreases in vitro microglial motility, beta1-integrin, and Kv1.3 channel expression. J. Neurochem. 103, 2035–2046 (2007). · DOI
  34. Song, J.-G. et al. Electroacupuncture improves survival in rats with lethal endotoxemia via the autonomic nervous system. Anesthesiology 116, 406–414 (2012). · DOI
  35. Liu, Z. et al. Effect of electroacupuncture on urinary leakage among women with stress urinary incontinence: a randomized clinical trial. JAMA 317, 2493–2501 (2017). · DOI
  36. Rusy, L. M., Hoffman, G. M. & Weisman, S. J. Electroacupuncture prophylaxis of postoperative nausea and vomiting following pediatric tonsillectomy with or without adenoidectomy. Anesthesiology 96, 300–305 (2002). · DOI
  37. Yuan, S. et al. The effects of electroacupuncture treatment on the postoperative cognitive function in aged rats with acute myocardial ischemia-reperfusion. Brain Res. 1593, 19–29 (2014). · DOI
  38. Feng, P.-P. et al. Electroacupuncture alleviates postoperative cognitive dysfunction in aged rats by inhibiting hippocampal neuroinflammation activated via microglia/TLRs pathway. Evid. Based Complement. Alternat. Med. 2017, 6421260 (2017).
  39. Hayhoe, S. Postoperative benefits with electroacupuncture. Acupunct. Med. 28, 64–64 (2010). · DOI
  40. Chen, Y. et al. Electroacupuncture pretreatment with different waveforms prevents brain injury in rats subjected to cecal ligation and puncture via inhibiting microglial activation, and attenuating inflammation, oxidative stress and apoptosis. Brain Res. Bull. 127, 248–259 (2016). · DOI
  41. Nimmervoll, B. et al. LPS-induced microglial secretion of TNFα increases activity-dependent neuronal apoptosis in the neonatal cerebral cortex. Cereb. Cortex 23, 1742–1755 (2013). · DOI
  42. Silva, S. L. et al. Neuritic growth impairment and cell death by unconjugated bilirubin is mediated by NO and glutamate, modulated by microglia, and prevented by glycoursodeoxycholic acid and interleukin-10. Neuropharmacology 62, 2398–2408 (2012). · DOI
  43. Abudara, V. et al. Activated microglia impairs neuroglial interaction by opening Cx43 hemichannels in hippocampal astrocytes. Glia 63, 795–811 (2015). · DOI
  44. Hovens, I. B. et al. Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiol. Learn. Mem. 118, 74–79 (2015). · DOI
  45. Parisi, C. et al. Dysregulated microRNAs in amyotrophic lateral sclerosis microglia modulate genes linked to neuroinflammation. Cell Death Dis. 4, e959 (2013). · DOI
  46. Jadhav, S. P., Kamath, S. P., Choolani, M., Lu, J. & Dheen, S. T. microRNA-200b modulates microglia-mediated neuroinflammation via the cJun/MAPK pathway. J. Neurochem. 130, 388–401 (2014). · DOI
  47. Murray, R. Z. A role for the phagosome in cytokine secretion. Science 310, 1492–1495 (2005). · DOI · Paper page
  48. Puri, C., Renna, M., Bento, C. F., Moreau, K. & Rubinsztein, D. C. Diverse autophagosome membrane sources coalesce in recycling endosomes. Cell 154, 1285–1299 (2013). · DOI
  49. Burm, S. M. et al. Inflammasome-induced IL-1β secretion in microglia is characterized by delayed kinetics and is only partially dependent on inflammatory caspases. J. Neurosci. 35, 678–687 (2015). · DOI · Paper page
  50. Davalos, D. et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8, 752–758 (2005). · DOI · Paper page
  51. Walker, F. R., Nilsson, M. & Jones, K. Acute and chronic stress-induced disturbances of microglial plasticity, phenotype and function. Curr. Drug Targets 14, 1262–1276 (2013). · DOI
  52. Sugama, S., Takenouchi, T., Fujita, M., Kitani, H. & Hashimoto, M. Cold stress induced morphological microglial activation and increased IL-1β expression in astroglial cells in rat brain. J. Neuroimmunol. 233, 29–36 (2011). · DOI · Paper page
  53. Blandino, P. Jr et al. Gene expression changes in the hypothalamus provide evidence for regionally-selective changes in IL-1 and microglial markers after acute stress. Brain Behav. Immun. 23, 958–968 (2009). · DOI · Paper page
  54. Frank, M. G., Baratta, M. V., Sprunger, D. B., Watkins, L. R. & Maier, S. F. Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav. Immun. 21, 47–59 (2007). · DOI · Paper page
  55. Mi, W.-L. et al. Involvement of spinal neurotrophin-3 in electroacupuncture analgesia and inhibition of spinal glial activation in rat model of monoarthritis. J. Pain 12, 974–984 (2011). · DOI
  56. Willemen, H. L. D. M. et al. MicroRNA-124 as a novel treatment for persistent hyperalgesia. J. Neuroinflammation 9, 143 (2012). · DOI · Paper page
  57. Hamzei Taj, S. et al. Dynamic modulation of microglia/macrophage polarization by miR-124 after focal cerebral ischemia. J. Neuroimmune Pharmacol. 11, 733–748 (2016). · DOI
  58. Panagiotis, Z., Georgios, V. & Dimitrios, R. The role of electroacupuncture in stroke treatment: a systematic review of the literature. J. Neurosci. Behavioral Health 7, 40–47 (2015). · DOI
  59. Zeng, L., Tao, Y., Hou, W., Zong, L. & Yu, L. Electro-acupuncture improves psychiatric symptoms, anxiety and depression in methamphetamine addicts during abstinence: a randomized controlled trial. Medicine 97, e11905 (2018). · DOI
  60. Yeung, W.-F. et al. Electroacupuncture for residual insomnia associated with major depressive disorder: a randomized controlled trial. Sleep 34, 807–815 (2011). · DOI

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Metadata

Authors
Chen, Y., Sun, J.-X., Chen, W.-K., Wu, G.-C., Wang, Y.-Q., Zhu, K.-Y., & Wang, J.
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2019-08-16
Volume
4
Issue
1
ISSN
2059-3635
DOI
10.1038/s41392-019-0061-x
PMC
PMC6799846
Cited by
74
References
3
Language
en
Licence
Funders
  • China Scholarship Council (201700260280)
  • National Natural Science Foundation of China (81871591, 81202746)

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