https://doi.org/10.4081/ejh.2023.3766
Dexmedetomidine attenuates neuroinflammation and microglia activation in LPS-stimulated BV2 microglia cells through targeting circ-Shank3/miR-140-3p/TLR4 axis
Submitted: 4 May 2023
Accepted: 13 June 2023
Published: 26 July 2023
Accepted: 13 June 2023
Abstract Views: 800
PDF: 728
HTML: 4
HTML: 4
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
It has been shown that dexmedetomidine (Dex) could attenuate postoperative cognitive dysfunction (POCD) via targeting circular RNAs (circRNAs). Circ-Shank3 has been found to be involved in the neuroprotective effects of Dex against POCD. However, the role of circ-Shank3 in POCD remains largely unknown. Reverse transcription quantitative PCR (RT-qPCR) was performed to detect circ-Shank3 and miR-140-3p levels in lipopolysaccharide (LPS)-treated microglia BV-2 cells in the absence or presence of Dex. The relationship among circ-Shank3, miR-140-3p and TLR4 was confirmed by dual-luciferase reporter assay. Additionally, Western blot and immunofluorescence (IF) assays were conducted to evaluate TLR4, p65 and Iba-1 or CD11b levels in cells. In this study, we found that Dex notably decreased circ-Shank3 and TLR4 levels and elevated miR-140-3p level in LPS-treated BV2 cells. Mechanistically, circ-Shank3 harbor miR-140-3p, functioning as a miRNA sponge, and then miR-140-3p targeted the 3’-UTR of TLR4. Additionally, Dex treatment significantly reduced TLR4 level and phosphorylation of p65, and decreased the expressions of microglia markers Iba-1 and CD11b in LPS-treated BV2 cells. As expected, silenced circ-Shank3 further reduced TLR4, p65 and Iba-1 and CD11b levels in LPS-treated BV2 cells in the presence of Dex, whereas these phenomena were reversed by miR-140-3p inhibitor. Collectively, our results found that Dex could attenuate the neuroinflammation and microglia activation in BV2 cells exposed to LPS via targeting circ-Shank3/miR-140-3p/TLR4 axis. Our results might shed a new light on the mechanism of Dex for the treatment of POCD.
Lin X, Chen Y, Zhang P, Chen G, Zhou Y, Yu X. The potential mechanism of postoperative cognitive dysfunction in older people. Exp Gerontol 2020;130:110791.
DOI: https://doi.org/10.1016/j.exger.2019.110791
Qiu LL, Pan W, Luo D, Zhang GF, Zhou ZQ, Sun XY, et al. Dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca(2+)/calpain might contribute to postoperative cognitive dysfunction in aging mice. J Neuroinflammation 2020;17:23.
DOI: https://doi.org/10.1186/s12974-019-1695-x
Borchers F, Spies CD, Feinkohl I, Brockhaus WR, Kraft A, Kozma P, et al. Methodology of measuring postoperative cognitive dysfunction: a systematic review. Br J Anaesth 2021;126:1119-27.
DOI: https://doi.org/10.1016/j.bja.2021.01.035
Yang XD, Wang LK, Wu HY, Jiao L. Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis. BMC Anesthesiol 2018;18:177.
DOI: https://doi.org/10.1186/s12871-018-0642-1
Subramaniyan S, Terrando N. Neuroinflammation and perioperative neurocognitive disorders. Anesth Analg 2019;128:781-8.
DOI: https://doi.org/10.1213/ANE.0000000000004053
Luo T, Hao YN, Lin DD, Huang X, Wu AS. Ginkgolide B improved postoperative cognitive dysfunction by inhibiting microgliosis-mediated neuroinflammation in the hippocampus of mice. BMC Anesthesiol 2022;22:229.
DOI: https://doi.org/10.1186/s12871-022-01750-1
Sun L, Yong Y, Wei P, Wang Y, Li H, Zhou Y, et al. Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice. CNS Neurosci Ther 2022;28:390-400.
DOI: https://doi.org/10.1111/cns.13784
Zhou H, Luo T, Wei C, Shen W, Li R, Wu A. RAGE antagonism by FPS‑ZM1 attenuates postoperative cognitive dysfunction through inhibition of neuroinflammation in mice. Mol Med Rep 2017;16:4187-94.
DOI: https://doi.org/10.3892/mmr.2017.7074
Bao Y, Zhu Y, He G, Ni H, Liu C, Ma L, et al. Dexmedetomidine attenuates neuroinflammation in LPS-stimulated BV2 microglia cells through upregulation of miR-340. Drug Des Devel Ther. 2019;13:3465-75.
DOI: https://doi.org/10.2147/DDDT.S210511
Wang YL, Zhang Y, Cai DS. Dexmedetomidine ameliorates postoperative cognitive dysfunction via the microRNA-381-mediated EGR1/p53 axis. Mol Neurobiol 2021;58:5052-66.
DOI: https://doi.org/10.1007/s12035-021-02417-7
Zhou WY, Cai ZR, Liu J, Wang DS, Ju HQ, Xu RH. Circular RNA: metabolism, functions and interactions with proteins. Mol Cancer 2020;19:172.
DOI: https://doi.org/10.1186/s12943-020-01286-3
Feng H, Yousuf S, Liu T, Zhang X, Huang W, Li A, et al. The comprehensive detection of miRNA and circRNA in the regulation of intramuscular and subcutaneous adipose tissue of Laiwu pig. Sci Rep 2022;12:16542.
DOI: https://doi.org/10.1038/s41598-022-21045-2
Ni S, Jiang T, Hao S, Luo P, Wang P, Almatari Y, et al. circRNA expression pattern and ceRNA network in the pathogenesis of aseptic loosening after total hip arthroplasty. Int J Med Sci 2021;18:768-77.
DOI: https://doi.org/10.7150/ijms.48014
Qian X, Zheng S, Yu Y. CircUBE3B high expression participates in sevoflurane-induced human hippocampal neuron injury via targeting miR-326 and regulating MYD88 expression. Neurotox Res 2023;41:16-28.
DOI: https://doi.org/10.1007/s12640-022-00617-0
Cao C, Deng F, Hu Y. Dexmedetomidine alleviates postoperative cognitive dysfunction through circular RNA in aged rats. 3 Biotech 2020;10:176.
DOI: https://doi.org/10.1007/s13205-020-2163-0
Zhang J, Yin J, Chen X, Mao X, Xu J, Cheng R, et al. Down-regulation of miR-140-3p can alleviate neonatal repetitive pain in rats via inhibiting TGF-β3. Biochem Biophys Res Commun 2019;515:627-35.
DOI: https://doi.org/10.1016/j.bbrc.2019.05.133
Cheng F, Qin W, Yang AX, Yan FF, Chen Y, Ma JX. Propofol alleviates neuropathic pain in chronic constriction injury rat models via the microRNA-140-3p/Jagged-1 peptide/Notch signaling pathway. Synapse 2021;75:e22219.
DOI: https://doi.org/10.1002/syn.22219
Wu Z, Tan J, Lin L, Zhang W, Yuan W. microRNA-140-3p protects hippocampal neuron against pyroptosis to attenuate sevoflurane inhalation-induced post-operative cognitive dysfunction in rats via activation of HTR2A/ERK/Nrf2 axis by targeting DNMT1. Cell Death Discov 2022;8:290.
DOI: https://doi.org/10.1038/s41420-022-01068-4
Wang Z, Huang C, Zhao C, Zhang H, Zhen Z, Xu D. Knockdown of LINC01385 inhibits osteoarthritis progression by modulating the microRNA-140-3p/TLR4 axis. Exp Ther Med 2021;22:1244.
DOI: https://doi.org/10.3892/etm.2021.10679
Xu Y, Yang B, Hu Y, Lu L, Lu X, Wang J, et al. Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush. Oncotarget 2016;7:72503-17.
DOI: https://doi.org/10.18632/oncotarget.12700
Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T, et al. CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis 2018;9:417.
DOI: https://doi.org/10.1038/s41419-018-0454-8
Yu L, Sun L, Chen S. Protective effect of senegenin on splenectomy-induced postoperative cognitive dysfunction in elderly rats. Exp Ther Med 2014;7:821-6.
DOI: https://doi.org/10.3892/etm.2014.1501
El-Sahar AE, Shiha NA, El Sayed NS, Ahmed LA. Alogliptin Attenuates lipopolysaccharide-induced neuroinflammation in mice through modulation of TLR4/MYD88/NF-κB and miRNA-155/SOCS-1 signaling pathways. Int J Neuropsychopharmacol 2021;24:158-69.
DOI: https://doi.org/10.1093/ijnp/pyaa078
Tan X, Tu Z, Han W, Song X, Cheng L, Chen H, et al. Anticonvulsant and neuroprotective effects of dexmedetomidine on pilocarpine-induced status epilepticus in rats using a metabolomics approach. Med Sci Monit 2019;25:2066-78.
DOI: https://doi.org/10.12659/MSM.912283
Tasbihgou SR, Barends CRM, Absalom AR. The role of dexmedetomidine in neurosurgery. Best Pract Res Clin Anaesthesiol 2021;35:221-9.
DOI: https://doi.org/10.1016/j.bpa.2020.10.002
Zhang Y, Gao Q, Wu Z, Xue H, Liu B, Zhao P. Dexmedetomidine promotes hippocampal neurogenesis and improves spatial learning and memory in neonatal rats. Drug Des Devel Ther 2019;13:4439-49.
DOI: https://doi.org/10.2147/DDDT.S228220
Lv H, Li Y, Cheng Q, Chen J, Chen W. Neuroprotective effects against cerebral ischemic injury exerted by dexmedetomidine via the HDAC5/NPAS4/MDM2/PSD-95 axis. Mol Neurobiol 2021;58:1990-2004.
DOI: https://doi.org/10.1007/s12035-020-02223-7
Liu YF, Hu R, Zhang LF, Fan Y, Xiao JF, Liao XZ. Effects of dexmedetomidine on cognitive dysfunction and neuroinflammation via the HDAC2/HIF-1α/PFKFB3 axis in a murine model of postoperative cognitive dysfunction. J Biochem Mol Toxicol 2022;36:e23044.
DOI: https://doi.org/10.1002/jbt.23044
Colonna M, Butovsky O. Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol 2017;35:441-68.
DOI: https://doi.org/10.1146/annurev-immunol-051116-052358
Wolf SA, Boddeke HW, Kettenmann H. Microglia in physiology and disease. Annu Rev Physiol 2017;79:619-43.
DOI: https://doi.org/10.1146/annurev-physiol-022516-034406
Ismail EN, Jantan I, Vidyadaran S, Jamal JA, Azmi N. Phyllanthus amarus prevents LPS-mediated BV2 microglial activation via MyD88 and NF-κB signaling pathways. BMC Complement Med Ther 2020;20:202.
DOI: https://doi.org/10.1186/s12906-020-02961-0
Phillips TEJ, Maguire E. Phosphoinositides: roles in the development of microglial-mediated neuroinflammation and neurodegeneration. Front Cell Neurosci 2021;15:652593.
DOI: https://doi.org/10.3389/fncel.2021.652593
Cardozo PL, de Lima IBQ, Maciel EMA, Silva NC, Dobransky T, Ribeiro FM. Synaptic elimination in neurological disorders. Curr Neuropharmacol 2019;17:1071-95.
DOI: https://doi.org/10.2174/1570159X17666190603170511
Ha Sen Ta N, Nuo M, Meng QT, Xia ZY. The pathway of Let-7a-1/2-3p and HMGB1 mediated dexmedetomidine inhibiting microglia activation in spinal cord ischemia-reperfusion injury mice. J Mol Neurosci 2019;69:106-14.
DOI: https://doi.org/10.1007/s12031-019-01338-4
Zhang MX, Lin JR, Yang ST, Zou J, Xue Y, Feng CZ, et al. Characterization of circRNA-associated-ceRNA networks involved in the pathogenesis of postoperative cognitive dysfunction in aging mice. Front Aging Neurosci 2022;14:727805.
DOI: https://doi.org/10.3389/fnagi.2022.727805
Zhou XY, Liu J, Xu ZP, Fu Q, Wang PQ, Zhang H. Dexmedetomidine inhibits the lipopolysaccharide-stimulated inflammatory response in microglia through the pathway involving TLR4 and NF-κB. Kaohsiung J Med Sci 2019;35:750-6.
DOI: https://doi.org/10.1002/kjm2.12112
Zhou XY, Liu J, Xu ZP, Fu Q, Wang PQ, Wang JH, et al. Dexmedetomidine ameliorates postoperative cognitive dysfunction by inhibiting Toll-like receptor 4 signaling in aged mice. Kaohsiung J Med Sci 2020;36:721-31.
DOI: https://doi.org/10.1002/kjm2.12234
Supporting Agencies
Shanghai Municipal Jiading District New Key Subject Program, Shanghai Municipal Jiading District Natural Science Research ProgramHow to Cite
He, G., He, Y., Ni, H., Wang, K., Zhu, Y., & Bao, Y. (2023). Dexmedetomidine attenuates neuroinflammation and microglia activation in LPS-stimulated BV2 microglia cells through targeting circ-Shank3/miR-140-3p/TLR4 axis. European Journal of Histochemistry, 67(3). https://doi.org/10.4081/ejh.2023.3766
Copyright (c) 2023 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- G. Scarsella, M. Nebbioso, S. Stefanini, N. Pescosolido, Degenerative effects in rat eyes after experimental ocular hypertension , European Journal of Histochemistry: Vol. 56 No. 4 (2012)
- Tao Wu, Shikui Wu, Hailu Jiao, Jun Feng, Xiang Zeng, Overexpression of hsa_circ_0001861 inhibits pulmonary fibrosis through targeting miR-296-5p/BCL-2 binding component 3 axis , European Journal of Histochemistry: Vol. 67 No. 4 (2023)
- Kazuhiko Hashimoto, Shunji Nishimura, Tomohiko Ito, Masao Akagi, Characterization of PD-1/PD-L1 immune checkpoint expression in soft tissue sarcomas , European Journal of Histochemistry: Vol. 65 No. 3 (2021)
- G. Lattanzi, S. Marmiroli, A. Facchini, N.M. Maraldi, Nuclear damages and oxidative stress: new perspectives for laminopathies , European Journal of Histochemistry: Vol. 56 No. 4 (2012)
- Guoyue Liu, Cunzhi Yin, Mingjiang Qian, Xuan Xiao, Hang Wu, Fujian Fu, LncRNA gadd7 promotes mitochondrial membrane potential decrease and apoptosis of alveolar type II epithelial cells by positively regulating MFN1 in an in vitro model of hyperoxia-induced acute lung injury , European Journal of Histochemistry: Vol. 67 No. 2 (2023)
- Liying Shen, Kongjie Lu, Zhenfeng Chen, Yingwei Zhu, Cong Zhang, Li Zhang, Pre-treatment with galectin-1 attenuates lipopolysaccharide-induced myocarditis by regulating the Nrf2 pathway , European Journal of Histochemistry: Vol. 67 No. 4 (2023)
- Francesca Diomede, Soundara Rajan Thangavelu, Ilaria Merciaro, Monica D'Orazio, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani, Porphyromonas gingivalis lipopolysaccharide stimulation in human periodontal ligament stem cells: role of epigenetic modifications to the inflammation , European Journal of Histochemistry: Vol. 61 No. 3 (2017)
- Valentina Alda Carozzi, Chiara Salio, Virginia Rodriguez-Menendez, Elisa Ciglieri, Francesco Ferrini, 2D vs 3D morphological analysis of dorsal root ganglia in health and painful neuropathy , European Journal of Histochemistry: Vol. 65 No. s1 (2021): Special Collection on Advances in Neuromorphology in Health and Disease
- M. Chiusa, F. Timolati, J.C. Perriard, T.M. Suter, C. Zuppinger, Sodium nitroprusside induces cell death and cytoskeleton degradation in adult rat cardiomyocytes in vitro: implications for anthracycline-induced cardiotoxicity , European Journal of Histochemistry: Vol. 56 No. 2 (2012)
- Jinbi Xie, Yong Ning, Lihang Zhang, Yuan Lin, Runsheng Guo, Shanjuan Wang, Overexpression of hsa_circ_0006470 inhibits the malignant behavior of gastric cancer cells via regulation of miR-1234/TP53I11 axis , European Journal of Histochemistry: Vol. 66 No. 4 (2022)
<< < 1 2 3 4 5 6 7 8 9 10 > >>
You may also start an advanced similarity search for this article.
