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Siglec-E Ligand Downregulation on Hippocampus Neurons Induced Inflammation in Sevoflurane-Associated Perioperative Neurocognitive Disorders in Aged Mice

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Abstract

Activated microglia-induced inflammation in the hippocampus plays an important role in perioperative neurocognitive disorders. Previous studies have shown that sialic acid-binding immunoglobulin-like lectin 3 (hSiglec-3, ortholog of mouse Siglec-E) engagement in microglia and its glycan ligands on neurons contributes to inflammatory homeostasis through an endogenous negative regulation pathway. This study aimed to explore whether the glycan ligand alteration on neurons plays a role in sevoflurane-induced perioperative neurocognitive disorders. This study’s data has shown that a slight Siglec-E ligands’ expression decrease does not induce inflammation homeostasis disruption. We also demonstrated that the ligand level on neurons was decreased with age, and the reduced Siglec-E ligand expression on neurons caused via sevoflurane was induced by neuraminidase 1. Furthermore, this study has shown that the Siglec-E ligand expression decline caused by age and sevoflurane treatment could decrease the ligands’ level, thus leading to inflammatory homeostasis disruption. This research provided a novel mechanism for perioperative neurocognitive disorder susceptibility in the elderly.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. van Harten, A.E., T.W. Scheeren, and A.R. Absalom. 2012. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia 67: 280–293. https://doi.org/10.1111/j.1365-2044.2011.07008.x.

    Article  PubMed  Google Scholar 

  2. Zhang, Y., G.J. Shan, Y.X. Zhang, S.J. Cao, S.N. Zhu, H.J. Li, D. Ma, and D.X. Wang. 2018. Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults. British Journal Anaesthesia 121: 595–604. https://doi.org/10.1016/j.bja.2018.05.059.

    Article  CAS  Google Scholar 

  3. Nemeth, E., K. Vig, K. Racz, K. Koritsanszky, K. Ronkay, F. Hamvaset, C. Borbély, A. Eory, B. Merkely, and J. Gal. 2017. Influence of the postoperative inflammatory response on cognitive decline in elderly patients undergoing on-pump cardiac surgery: A controlled, prospective observational study. BMC Anesthesiology 17: 113. https://doi.org/10.1186/s12871-017-0408-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vutskits, L., and Z. Xie. 2016. Lasting impact of general anaesthesia on the brain: Mechanisms and relevance. Nature Reviews Neuroscience 17: 705–717. https://doi.org/10.1038/nrn.2016.128.

    Article  CAS  PubMed  Google Scholar 

  5. Alvarado, M.C., K.L. Murphy, and M.G. Baxter. 2017. Visual recognition memory is impaired in rhesus monkeys repeatedly exposed to sevoflurane in infancy. British Journal of Anaesthesia 119: 517–523. https://doi.org/10.1093/bja/aew473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fan, C.H., B. Peng, and F. Zhang. 2018. The postoperative effect of sevoflurane inhalational anesthesia on cognitive function and inflammatory response of pediatric patients. European Review for Medical and Pharmacological Sciences 22: 3971–3975. https://doi.org/10.26355/eurrev_201806_15281.

  7. Thiesler, H., J. Beimdiek, and H. Hildebrandt. 2021. Polysialic acid and Siglec-E orchestrate negative feedback regulation of microglia activation. Cellular and Molecular Life Sciences 78: 1637–1653. https://doi.org/10.1007/s00018-020-03601-z.

    Article  CAS  PubMed  Google Scholar 

  8. Li, L., Y. Chen, M.N. Sluter, R. Hou, J. Hao, Y. Wu, G.Y. Chen, Y. Yu, and J. Jiang. 2022. Ablation of Siglec-E augments brain inflammation and ischemic injury. Journal of Neuroinflammation 19: 191. https://doi.org/10.1186/s12974-022-02556-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Linnartz-Gerlach, B., M. Mathews, and H. Neumann. 2014. Sensing the neuronal glycocalyx by glial sialic acid binding immunoglobulin-like lectins. Neuroscience 275: 113–124. https://doi.org/10.1016/j.neuroscience.2014.05.061.

    Article  CAS  PubMed  Google Scholar 

  10. Siddiqui, S.S., R. Matar, M. Merheb, R. Hodeify, C.G. Vazhappilly, J. Marton, S.A. Shamsuddin, and H.A. Zouabi. 2019. Siglecs in brain function and neurological disorders. Cells 8: 1125. https://doi.org/10.3390/cells8101125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Claude, J., B. Linnartz-Gerlach, A.P. Kudin, W.S. Kunz, and H. Neumann. 2013. Microglial CD33-related Siglec-E inhibits neurotoxicity by preventing the phagocytosis-associated oxidative burst. Journal of Neuroscience 33: 18270–18276. https://doi.org/10.1523/JNEUROSCI.2211-13.2013.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang, Y., Y. Zheng, J. Li, L. Nie, Y. Hu, F. Wang, H. Liu, S.M. Fernandes, Q. Zhong, X. Li, R.L. Schnaar, and Y. Jia. 2019. Immunoregulatory Siglec ligands are abundant in human and mouse aorta and are up-regulated by high glucose. Life Sciences 216: 189–199. https://doi.org/10.1016/j.lfs.2018.11.049.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou, Y.T., J. Zhang, L. Wang, Y. Chen, Y.S. Wan, Y. He, L. Jiang, J. Ma, R.J. Liao, X.N. Zhang, L.Y. Shi, Z.H. Qin, Y.D. Zhou, Z. Chen, and W.W. Hu. 2017. Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion. Brain, Behavior, and Immunity 60: 93–105. https://doi.org/10.1016/j.bbi.2016.09.024.

  14. Liao, R.J., Y.C. Chen, L. Cheng, L.S. Fan, H. Chen, Y.S. Wan, Y. You, Y.R. Zheng, L. Jiang, Z. Chen, X.N. Zhang, and W.W. Hu. 2019. Histamine H1 receptors in neural stem cells are required for the promotion of neurogenesis conferred by H3 receptor antagonism following traumatic brain injury. Stem Cell Reports. 12: 532–544. https://doi.org/10.1016/j.stemcr.2019.01.004.

  15. Feng, X., M. Valdearcos, Y. Uchida, D. Lutrin, M. Maze, and S.K. Koliwad. 2017. Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice. JCI Insight 2: e91229. https://doi.org/10.1172/jci.insight.91229.

  16. Ge, X., Y. Zuo, J. Xie, X. Li, Y. Li, A. Thirupathi, P. Yu, G. Gao, C. Zhou, Y. Chang, and Z. Shi. 2021. A new mechanism of POCD caused by sevoflurane in mice: cognitive impairment induced by cross-dysfunction of iron and glucose metabolism. Aging (Albany NY) 13: 22375–22389. https://doi.org/10.18632/aging.203544.

  17. Zhu, R., S. Zeng, N. Li, N. Fu, Y. Wang, M. Miao, Y. Yang, M. Sun, and J. Zhang. 2022. Sevoflurane exposure induces neurotoxicity by regulating mitochondrial function of microglia due to NAD insufficiency. Frontiers in Cellular Neuroscience 16: 914957. https://doi.org/10.3389/fncel.2022.914957.

  18. Cui, R.S., K. Wang, and Z.L. Wang. 2018. Sevoflurane anesthesia alters cognitive function by activating inflammation and cell death in rats. Experimental and Therapeutic Medicine 15: 4127–4130. https://doi.org/10.3892/etm.2018.5976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Li, Q., Y. Zhao, C. Shi, and X. Song. 2022. IL-33 alleviates postoperative cognitive impairment by inhibiting hippocampal inflammation and upregulating excitatory synaptic number in aged mice. Brain Sciences 12: 1244. https://doi.org/10.3390/brainsci12091244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tian, Y., S. Guo, Y. Zhang, Y. Xu, P. Zhao, and X. Zhao. 2017. Effects of hydrogen-rich saline on hepatectomy-induced postoperative cognitive dysfunction in old mice. Molecular Neurobiology 54: 2579–2584. https://doi.org/10.1007/s12035-016-9825-2.

    Article  CAS  PubMed  Google Scholar 

  21. Wang, F., C. Li, J. Shao, and J. Ma. 2021. Sevoflurane induces inflammation of microglia in hippocampus of neonatal rats by inhibiting Wnt/β-Catenin/CaMKIV pathway. Journal of Pharmacological Sciences 146: 105–115. https://doi.org/10.1016/j.jphs.2021.02.004.

    Article  CAS  PubMed  Google Scholar 

  22. Zhao, W., S. Song, W. Chu, Y. Li, S. Chen, Y. Ji, Q. Chen, X. Jin, and F. Ji. 2022. Disruption of hippocampal P2RX2/CaMKII/NF-κB signaling contributes to learning and memory impairment in C57BL/6 mice induced by surgery plus anesthesia in neonatal period. Biomed Pharmacother 149: 112897. https://doi.org/10.1016/j.biopha.2022.112897.

  23. Chen, H., H. Chu, Q. Jiang, C. Wang, and Y. Tian. 2021. Irf6 participates in sevoflurane-induced perioperative neurocognitive disorder via modulating M2, but not M1 polarization of microglia. Brain Research Bulletin 177: 1–11. https://doi.org/10.1016/j.brainresbull.2021.09.012.

    Article  CAS  PubMed  Google Scholar 

  24. Lin, C.H., Y.C. Yeh, and K.D. Yang. 2021. Functions and therapeutic targets of Siglec-mediated infections, inflammations and cancers. Journal of the Formosan Medical Association 120: 5–24. https://doi.org/10.1016/j.jfma.2019.10.019.

    Article  CAS  PubMed  Google Scholar 

  25. Gonzalez-Gil, A., and R.L. Schnaar. 2021. Siglec ligands. Cells 10: 1260. https://doi.org/10.3390/cells10051260.

    Article  CAS  PubMed  Google Scholar 

  26. Zhang, J.Q., B. Biedermann, L. Nitschke, and P.R. Crocker. 2004. The murine inhibitory receptor mSiglec-E is expressed broadly on cells of the innate immune system whereas mSiglec-F is restricted to eosinophils. European Journal of Immunology 34: 1175–1184. https://doi.org/10.1002/eji.200324723.

    Article  CAS  PubMed  Google Scholar 

  27. Vuchkovska, A., D.G. Glanville, G.M. Scurti, M.I. Nishimura, P. White, A.T. Ulijasz, and M. Iwashima. 2022. Siglec-5 is an inhibitory immune checkpoint molecule for human T cells. Immunology 166: 238–248. https://doi.org/10.1111/imm.13470.

    Article  CAS  PubMed  Google Scholar 

  28. Andes, F.T., S. Adam, M. Hahn, O. Aust, S. Frey, A. Grueneboom, L. Nitschke, G. Schett, and U. Steffen. 2021. The human sialic acid-binding immunoglobulin-like lectin Siglec-9 and its murine homolog Siglec-E control osteoclast activity and bone resorption. Bone 143: 115665. https://doi.org/10.1016/j.bone.2020.115665.

  29. Smith, B.A.H., and C.R. Bertozzi. 2021. The clinical impact of glycobiology: Targeting selectins, Siglecs and mammalian glycans. Nature Reviews. Drug Discovery 20: 217–243. https://doi.org/10.1038/s41573-020-00093-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wißfeld, J., I. Nozaki, M. Mathews, T. Raschka, C. Ebeling, V. Hornung, O. Brüstle, and H. Neumann. 2021. Deletion of Alzheimer’s disease-associated CD33 results in an inflammatory human microglia phenotype. Glia 69: 1393–1412. https://doi.org/10.1002/glia.23968.

    Article  CAS  PubMed  Google Scholar 

  31. Jia, Y., H. Yu, S.M. Fernandes, Y. Wei, A. Gonzalez-Gil, M.G. Motari, K. Vajn, W.W. Stevens, A.T. Peters, B.S. Bochner, R.C. Kern, R.P. Schleimer, and R.L. Schnaar. 2015. Expression of ligands for Siglec-8 and Siglec-9 in human airways and airway cells. The Journal of Allergy and Clinical Immunology 135: 799–810. https://doi.org/10.1016/j.jaci.2015.01.004.

    Article  CAS  PubMed  Google Scholar 

  32. Liu, H., Y. Zheng, Y. Zhang, J. Li, S.M. Fernandes, D. Zeng, X. Li, R.L. Schnaar, and Y. Jia. 2020. Immunosuppressive Siglec-E ligands on mouse aorta are up-regulated by LPS via NF-kappaB pathway. Biomed Pharmacother 122: 109760. https://doi.org/10.1016/j.biopha.2019.109760.

  33. Chen, G.Y., N.K. Brown, W. Wu, Z. Khedri, H. Yu, X. Chen, D. Vlekkert, A. D’Azzo, P. Zheng, and Y. Liu. 2014. Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1. Elife 3: e04066. https://doi.org/10.7554/eLife.04066.

  34. Ji, M.H., X. He, J.C. Shen, and J.J. Yang. 2021. Aging-related neural disruption might predispose to postoperative cognitive impairment following surgical trauma. Journal of Alzheimer’s Disease 81: 1685–1699. https://doi.org/10.3233/JAD-201590.

    Article  PubMed  Google Scholar 

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81971018), the 345 Talent Project of Shengjing Hospital of China Medical University, and the Applied Basic Research Plan of Liaoning Province (Joint Plan, 2022JH2/101500065).

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Yue Tian and Yi Jia designed the research. Xiaoli Zhang and Xueting Wang performed the cell experiments and flow cytometry. Ziyang Xu contributed to the animal treatment and cognitive function analysis. Fengwei Sun performed immunofluorescence. Xiaoli Zhang and Yue Tian wrote the manuscript. Yue Tian and Yi Jia revised the manuscript.

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Correspondence to Yue Tian.

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Zhang, X., Wang, X., Xu, Z. et al. Siglec-E Ligand Downregulation on Hippocampus Neurons Induced Inflammation in Sevoflurane-Associated Perioperative Neurocognitive Disorders in Aged Mice. Inflammation 47, 30–44 (2024). https://doi.org/10.1007/s10753-023-01888-1

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