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RETRACTED ARTICLE: Curcumin amends Ca2+ dysregulation in microglia by suppressing the activation of P2X7 receptor

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This article was retracted on 05 April 2024

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Abstract

Curcumin (Cur) is widely used as an anti-inflammation agent and has anti-depression potential. Neuroinflammation mediated by Ca2+ channel activation is closely associated with the progression of post-stroke depression (PSD). In the current study, the role of P2X7 receptor (P2X7R) in the anti-PSD function of Cur was explored. Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and chronic mild stress administration to induce PSD symptoms and then treated with Cur. The behaviors of rats were assessed with sucrose preference and forced swim tests. The accumulation of Ca2+ and the systemic inflammatory response in rats were detected. To determine the role of P2X7R in the anti-PSD function of curcumin, the PSD mice were further administrated with P2X7R agonist and antagonist. The administration of Cur attenuated behavior disorders associated with PSD. Moreover, the Ca2+ accumulation and the inflammatory response associated with PSD were also blocked by Cur. Cur also inhibited the activation of Ca2+ channel. The induced activity of P2X7R blocked the function of Cur by maintaining the symptoms of PSD in Cur-treated rats. Collectively, the anti-PSD function of Cur was dependent on the inhibition of P2X7R, which then deactivated Ca2+ channel-mediated inflammatory response associated with PSD progression.

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References

  1. Hackett ML, Yapa C, Parag V, Anderson CS (2005) Frequency of depression after stroke: a systematic review of observational studies. Stroke 36(6):1330–1340. https://doi.org/10.1161/01.STR.0000165928.19135.35

    Article  PubMed  Google Scholar 

  2. Ayerbe L, Ayis S, Wolfe CD, Rudd AG (2013) Natural history, predictors and outcomes of depression after stroke: systematic review and meta-analysis. Brit J Psychiatry 202(1):14–21. https://doi.org/10.1192/bjp.bp.111.107664

    Article  Google Scholar 

  3. Hackett ML, Anderson CS, House A, Xia J (2008) Interventions for treating depression after stroke. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.cd003437.pub3

    Article  PubMed  Google Scholar 

  4. Winstein CJ, Stein J, Arena R, Bates B, Cherney LR, Cramer SC, Deruyter F, Eng JJ, Fisher B, Harvey RL, Lang CE, MacKay-Lyons M, Ottenbacher KJ, Pugh S, Reeves MJ, Richards LG, Stiers W, Zorowitz RD (2016) Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 47(6):e98–e169. https://doi.org/10.1161/STR.0000000000000098

    Article  PubMed  Google Scholar 

  5. Loubinoux I, Kronenberg G, Endres M, Schumann-Bard P, Freret T, Filipkowski RK, Kaczmarek L, Popa-Wagner A (2012) Post-stroke depression: mechanisms, translation and therapy. J Cell Mol Med 16(9):1961–1969. https://doi.org/10.1111/j.1582-4934.2012.01555.x

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kiecolt-Glaser JK, Derry HM, Fagundes CP (2015) Inflammation: depression fans the flames and feasts on the heat. Am J Psychiatry 172(11):1075–1091. https://doi.org/10.1176/appi.ajp.2015.15020152

    Article  PubMed  PubMed Central  Google Scholar 

  7. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71(2):171–186. https://doi.org/10.1097/PSY.0b013e3181907c1b

    Article  CAS  PubMed  Google Scholar 

  8. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457. https://doi.org/10.1016/j.biopsych.2009.09.033

    Article  CAS  PubMed  Google Scholar 

  9. Liu Yang, Ho Chunman R, Mak Anselm (2012) Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: A meta-analysis and meta-regression. J Affect Disord 139(3):230–239

    Article  CAS  PubMed  Google Scholar 

  10. Yirmiya R, Rimmerman N, Reshef R (2015) Depression as a Microglial Disease. Trends Neurosci 38(10):637–658

    Article  CAS  PubMed  Google Scholar 

  11. Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A (2011) The role of microglia in the healthy brain. J Neurosci 31(45):16064–16069. https://doi.org/10.1523/JNEUROSCI.4158-11.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wake H, Moorhouse AJ, Miyamoto A, Nabekura J (2013) Microglia: actively surveying and shaping neuronal circuit structure and function. Trends Neurosci 36(4):209–217. https://doi.org/10.1016/j.tins.2012.11.007

    Article  CAS  PubMed  Google Scholar 

  13. Huang BR, Chang PC, Yeh WL, Lee CH, Tsai CF, Lin C, Lin HY, Liu YS, Wu CY, Ko PY, Huang SS, Hsu HC, Lu DY (2014) Anti-neuroinflammatory effects of the calcium channel blocker nicardipine on microglial cells: implications for neuroprotection. PLoS ONE 9(3):e91167. https://doi.org/10.1371/journal.pone.0091167

    Article  PubMed  PubMed Central  Google Scholar 

  14. Liu Y, Lo YC, Qian L, Crews FT, Wilson B, Chen HL, Wu HM, Chen SH, Wei K, Lu RB (2011) Verapamil protects dopaminergic neuron damage through a novel anti-inflammatory mechanism by inhibition of microglial activation. Neuropharmacology 60(2–3):373–380

    Article  CAS  PubMed  Google Scholar 

  15. Srimal RC, Dhawan BN (1973) Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 25(6):447–452. https://doi.org/10.1111/j.2042-7158.1973.tb09131.x

    Article  CAS  PubMed  Google Scholar 

  16. Satoskar RR, Shah SJ, Shenoy SG (1986) Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol 24(12):651–654

    CAS  PubMed  Google Scholar 

  17. Sharma OP (1976) Antioxidant activity of curcumin and related compounds ☆. Biochem Pharmacol 25(15):1811–1812

    Article  CAS  PubMed  Google Scholar 

  18. Seo JA, Kim B, Dhanasekaran DN, Tsang BK, Song YS (2016) Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca2 + ATPase activity in ovarian cancer cells. Cancer Lett 371(1):30–37. https://doi.org/10.1016/j.canlet.2015.11.021

    Article  CAS  PubMed  Google Scholar 

  19. Zhang WY, Guo YJ, Han WX, Yang MQ, Wen LP, Wang KY, Jiang P (2019) Curcumin relieves depressive-like behaviors via inhibition of the NLRP3 inflammasome and kynurenine pathway in rats suffering from chronic unpredictable mild stress. Int Immunopharmacol 67:138–144. https://doi.org/10.1016/j.intimp.2018.12.012

    Article  CAS  PubMed  Google Scholar 

  20. Gombault A, Baron L, Couillin I (2013) ATP release and purinergic signaling in NLRP3 inflammasome activation. Front Immunol 3:414

    Article  PubMed  PubMed Central  Google Scholar 

  21. Madiha S, Haider S (2019) Curcumin restores rotenone induced depressive-like symptoms in animal model of neurotoxicity: assessment by social interaction test and sucrose preference test. Metab Brain Dis 34(1):297–308. https://doi.org/10.1007/s11011-018-0352-x

    Article  CAS  PubMed  Google Scholar 

  22. Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47(4):379–391. https://doi.org/10.1016/0014-2999(78)90118-8

    Article  CAS  PubMed  Google Scholar 

  23. Ng QX, Ssh K, Chan HW, Cyx H (2017) Clinical use of curcumin in depression: a meta-analysis. J Am Med Dir Assoc 18(6):503–508

    Article  PubMed  Google Scholar 

  24. Kaufmann FN, Gazal M, Bastos CR, Kaster MP, Ghisleni G (2016) Curcumin in depressive disorders: an overview of potential mechanisms, preclinical and clinical findings. Eur J Pharmacol 784:192–198

    Article  CAS  PubMed  Google Scholar 

  25. Farzanfar D, Dowlati Y, French LE, Lowes MA, Alavi A (2018) Inflammation: a contributor to depressive comorbidity in inflammatory skin disease. Skin Pharmacol Physiol 31(5):246–251. https://doi.org/10.1159/000490002

    Article  CAS  PubMed  Google Scholar 

  26. Czeh M, Gressens P, Kaindl AM (2011) The yin and yang of microglia. Dev Neurosci-Basel 33(3–4):199–209. https://doi.org/10.1159/000328989

    Article  CAS  Google Scholar 

  27. Wee Yong V (2010) Inflammation in neurological disorders: a help or a hindrance? Neuroscientist 16(4):408–420. https://doi.org/10.1177/1073858410371379

    Article  CAS  PubMed  Google Scholar 

  28. Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M (2006) Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nat Neurosci 9(2):268–275. https://doi.org/10.1038/nn1629

    Article  CAS  PubMed  Google Scholar 

  29. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82(4):1013–1067. https://doi.org/10.1152/physrev.00015.2002

    Article  CAS  PubMed  Google Scholar 

  30. Khakh BS, R Alan N (2006) P2X receptors as cell-surface ATP sensors in health and disease. Nature 442 (7102):527-532

  31. Dubyak GR (2007) Go it alone no more–P2X7 joins the society of heteromeric ATP-gated receptor channels. Mol Pharmacol 72(6):1402–1405

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by the grants from the Science and Technology Research Project of Henan Province (172102310585).

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Authors and Affiliations

  1. Department of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Jiankang Road, Weihui, Xinxiang, 453100, Henan, China

    Zhen Wang, Weihua Ren, Fucheng Zhao, Yanru Han, Caili Liu & Kui Jia

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  1. Zhen Wang
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  2. Weihua Ren
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Correspondence to Kui Jia.

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Zhen Wang and Kui Jia have contributed equally to this work.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s11010-024-05003-2"

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Wang, Z., Ren, W., Zhao, F. et al. RETRACTED ARTICLE: Curcumin amends Ca2+ dysregulation in microglia by suppressing the activation of P2X7 receptor. Mol Cell Biochem 465, 65–73 (2020). https://doi.org/10.1007/s11010-019-03668-8

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