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Apamin administration impact on miR-219 and miR-155-3p expression in cuprizone induced multiple sclerosis model

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Abstract

Multiple sclerosis (MS) is a chronic debilitating disease that attacks the central nervous system. This study aims to investigate miR-219 and miR-155-3p expression levels involved in the myelination process following the administration of apamin peptide in the model of multiple sclerosis disease. Forty-four 8 week C57BL/6 male mice (22 ± 5 g) randomly divided into six groups. Apamin (100 µg/kg/BW) was administered intraperitoneally as a co-treatment during phase I (demyelination) or post-treatment phase II (remyelination) twice a week in cuprizone induced MS model. At the end of study myelin content and microRNA expression levels were measured with LFB staining and quantitative Real-Time PCR method, respectively. It was observed that the intended microRNAs were dysregulated during the different phases of disease induction. After 6 weeks of cuprizone exposure, miR-219 downregulated in phase I in comparison with the negative control. On the other hand, the apamin co-treatment significantly inhibit the miR-155-3p upregulation during the phase I as compared with the cuprizone group (p < 0.0001). Apamin has more impact on the miR155-3p reduction in phase I than miR-219 elevation in phase II. It could be considered as a therapeutic option for decreasing plaque formation during the exacerbation phase of the MS disease. Apamin has more impact on the miR155-3p reduction in phase I than miR-219 elevation in phase II. It could be considered as a therapeutic option for decreasing plaque formation during the exacerbation phase of the MS disease.

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References

  1. Höftberger R, Lassmann H (2018) Inflammatory demyelinating diseases of the central nervous system. In: Handbook of clinical neurology, vol 145. Elsevier, pp 263–283

  2. Pugliatti M, Sotgiu S, Rosati G (2002) The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 104(3):182–191

    Article  Google Scholar 

  3. Yeung MSY et al (2019) Dynamics of oligodendrocyte generation in multiple sclerosis. Nature 566(7745):538

    Article  CAS  Google Scholar 

  4. Aliomrani M, Sahraian MA, Shirkhanloo H, Sharifzadeh M, Khoshayand MR, Ghahremani MH (2016) Blood concentrations of cadmium and lead in multiple sclerosis patients from Iran. Iran J Pharm Res 15(4):825

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Aliomrani M, Sahraian MA, Shirkhanloo H, Sharifzadeh M, Khoshayand MR, Ghahremani MH (2017) Correlation between heavy metal exposure and GSTM1 polymorphism in Iranian multiple sclerosis patients. Neurol Sci 38(7):1271–1278

    Article  Google Scholar 

  6. Fratellone PM, Tsimis F, Fratellone G (2016) Apitherapy products for medicinal use. J Altern Complement Med 22(12):1020–1022

    Article  Google Scholar 

  7. Giralt E (2017) Peptides as shuttles for drug delivery to the brain. In: Abstracts of papers of the American Chemical Society, vol 253

  8. Li C, Pazgier M, Liu M, Lu W, Lu W (2009) Apamin as a template for structure-based rational design of potent peptide activators of p53. Angew Chem 121(46):8868–8871

    Article  Google Scholar 

  9. Park J, Jang KM, Park K-K (2020) Apamin suppresses LPS-induced neuroinflammatory responses by regulating SK CHANNELS and TLR4-mediated signaling pathways. Int J Mol Sci 21(12):4319

    Article  CAS  Google Scholar 

  10. Hugues M, Romey G, Duval D, Vincent J-P, Lazdunski M (1982) Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor. Proc Natl Acad Sci 79(4):1308–1312

    Article  CAS  Google Scholar 

  11. Kim S-J et al (2012) The protective effect of apamin on LPS/fat-induced atherosclerotic mice. Evid-Based Complement Altern Med

  12. Zhao Y et al (2015) Toxins targeting the Kv1. 3 channel: potential immunomodulators for autoimmune diseases. Toxins 7(5):1749–1764

    Article  CAS  Google Scholar 

  13. Valle Reyes JS, Valencia Cruz G, Liñan Rico L, Pottosin I, Dobrovinskaya O (2018) Differential activity of voltage-and Ca2+-dependent potassium channels in leukemic T cell lines: Jurkat cells represent an exceptional case. Front Physiol 9:499

    Article  Google Scholar 

  14. Thei L, Imm J, Kaisis E, Dallas ML, Kerrigan TL (2018) Microglia in alzheimer’s disease: a role for ion channels. Front Neurosci 12(676):10–3389

    Google Scholar 

  15. Bozic I et al (2019) The potassium channel Kv1. 5 expression alters during experimental autoimmune encephalomyelitis. Neurochem Res 44(12):2733–2745

    Article  CAS  Google Scholar 

  16. Maldonado PP, Vélez-Fort M, Levavasseur F, Angulo MC (2013) Oligodendrocyte precursor cells are accurate sensors of local K+ in mature gray matter. J Neurosci 33(6):2432–2442

    Article  CAS  Google Scholar 

  17. de Planell-Saguer M, Rodicio MC (2011) Analytical aspects of microRNA in diagnostics: a review. Anal Chim Acta 699(2):134–152

    Article  Google Scholar 

  18. Dugas JC et al (2010) Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron 65(5):597–611

    Article  CAS  Google Scholar 

  19. Zhao X et al (2010) MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65(5):612–626

    Article  CAS  Google Scholar 

  20. Mazloumfard F, Mirian M, Eftekhari S-M, Aliomrani M (2020) Hydroxychloroquine effects on miR-155–3p and miR-219 expression changes in animal model of multiple sclerosis. Metab Brain Dis 1–9

  21. Moore CS et al (2013) miR-155 as a multiple sclerosis–relevant regulator of myeloid cell polarization. Ann Neurol 74(5):709–720

    Article  CAS  Google Scholar 

  22. Dong HW (2008) The Allen reference atlas: a digital color brain atlas of the C57Bl/6J male mouse. Wiley, New York

    Google Scholar 

  23. Junker A, Hohlfeld R, Meinl E (2011) The emerging role of microRNAs in multiple sclerosis. Nat Rev Neurol 7(1):56

    Article  CAS  Google Scholar 

  24. Siegel SR, Mackenzie J, Chaplin G, Jablonski NG, Griffiths L (2012) Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep 39(5):6219–6225

    Article  CAS  Google Scholar 

  25. Zhang J et al (2017) MiR-146a promotes remyelination in a cuprizone model of demyelinating injury. Neuroscience 348:252–263

    Article  CAS  Google Scholar 

  26. Mohammadi-Rad M, Ghasemi N, Aliomrani M (2019) Evaluation of apamin effects on myelination process in C57BL/6 mice model of multiple sclerosis. Res Pharm Sci 14(5):424. https://doi.org/10.4103/1735-5362.268203

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dugas JC, Notterpek L (2011) MicroRNAs in oligodendrocyte and Schwann cell differentiation. Dev Neurosci 33(1):14–20

    Article  CAS  Google Scholar 

  28. McCoy CE (2017) miR-155 dysregulation and therapeutic intervention in multiple sclerosis. In: Regulation of inflammatory signaling in health and disease. Springer,, pp 111–131.

  29. Dutta R et al (2013) Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors. Ann Neurol 73(5):637–645

    Article  CAS  Google Scholar 

  30. Chen C, Zhou Y, Wang J, Yan Y, Peng L, Qiu W (2018) Dysregulated microRNA involvement in multiple sclerosis by induction of T helper 17 cell differentiation. Front Immunol 9:1256

    Article  Google Scholar 

  31. Liu S et al (2017) miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1. Eur J Neurosci 45(2):249–259

    Article  Google Scholar 

  32. Yavarpour-Bali H, Nakhaei-Nejad M, Yazdi A, Ghasemi-Kasman M (2020) Direct conversion of somatic cells towards oligodendroglial lineage cells: a novel strategy for enhancement of myelin repair. J Cell Physiol 235(3):2023–2036

    Article  CAS  Google Scholar 

  33. Huang H, Zhao X-F, Zheng K, Qiu M (2013) Regulation of the timing of oligodendrocyte differentiation: mechanisms and perspectives. Neurosci Bull 29(2):155–164

    Article  CAS  Google Scholar 

  34. Lescher J et al (2012) MicroRNA regulation in experimental autoimmune encephalomyelitis in mice and marmosets resembles regulation in human multiple sclerosis lesions. J Neuroimmunol 246(1–2):27–33

    Article  CAS  Google Scholar 

  35. Henry RJ et al (2019) Inhibition of miR-155 limits neuroinflammation and improves functional recovery after experimental traumatic brain injury in mice. Neurotherapeutics 16(1):216–230

    Article  CAS  Google Scholar 

  36. Mycko MP, Cichalewska M, Cwiklinska H, Selmaj KW (2015) miR-155-3p drives the development of autoimmune demyelination by regulation of heat shock protein 40. J Neurosci 35(50):16504–16515

    Article  CAS  Google Scholar 

  37. Cardoso AL, Guedes JR, Pereira de Almeida L, Pedroso de Lima MC (2012) miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric oxide production. Immunology 135(1):73–88

    Article  CAS  Google Scholar 

  38. Ceppi M et al (2009) MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci 106(8):2735–2740

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by a grant (Project No. 297134) from Isfahan Pharmaceutical Science Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Funding

This study was supported by a grant (Project No. 297134) from Isfahan Pharmaceutical Science Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

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Authors

Contributions

SG and MAO conceived of the presented idea, SG and MM carried out the experiment, SME and MAO helped supervise the project, all authors provided critical feedback and helped shape the research, analysis and manuscript.

Corresponding author

Correspondence to Mehdi Aliomrani.

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All authors declare no conflict of interest.

Ethical approval

All procedures were approved by the Iran National Committee for Ethics in Biomedical Research (IR.MUI.RESEARCH.REC.1397.387) which was performed in accordance with the Guidelines for the Care and Use of Laboratory Animals.

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Gholami, S., Mirian, M., Eftekhari, S.M. et al. Apamin administration impact on miR-219 and miR-155-3p expression in cuprizone induced multiple sclerosis model. Mol Biol Rep 47, 9013–9019 (2020). https://doi.org/10.1007/s11033-020-05959-6

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  • DOI: https://doi.org/10.1007/s11033-020-05959-6

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