Advertisement

Journal of Molecular Neuroscience

, Volume 63, Issue 3–4, pp 275–282 | Cite as

Evaluation of Selected MicroRNAs Expression in Remission Phase of Multiple Sclerosis and Their Potential Link to Cognition, Depression, and Disability

  • Marta Niwald
  • Monika Migdalska-Sęk
  • Ewa Brzeziańska-Lasota
  • Elżbieta Miller
Article

Abstract

Accumulating data suggests that miRNAs might play a major role in neuroinflammatory processes. Therefore, our study aimed to first estimate the levels of miR-155, miR-326, and miR-301a in serum of RR-MS patients in the remission phase and then compare the levels of the examined miRNAs at different times after relapse. In this study, 36 RR-MS patients in the remission phase took part. We analyzed two subgroups of RR-MS: one, 1 to 2 months after completing steroid treatment during relapse (post-acute; n = 13) and the other, over 2 years without any relapse (stable; n = 23). Moreover, we made correlations between these biochemical results and clinical parameters of cognitive impairment, depression, and disability. The obtained results presented downregulation of miR-155 and miR-301a (in 94% and 51% samples, respectively) and overexpression of miR-326 (in 72% samples) in RR-MS patients. Moreover, we observed a positive correlation between the relative expression of miRNAs and BDI (Beck Depression Index) for miR-326 (rho = 0.385459, p = 0.022210; Spearman’s rank correlation) and miR-301a (rho = 0.435131, p = 0.008991; Spearman rank correlation). We also observed the differences in expression levels between the post-acute and stable phases of RR-MS. The expression levels of miR-301a and miR155 were higher in the post-acute vs. stable phase of remission (2.385 vs. 0.524 and 0.594 vs. 0.147; respectively). Our study, for the first time, presents miRNA expression differences in two stages of remission: post-acute and stable.

Keywords

Multiple sclerosis Remission miRNA Depression Disability Cognition 

Notes

Acknowledgements

We thank all subjects for participating in this study and all of our colleagues in the Neurorehabilitation Ward in the III General Hospital of Lodz, Poland.

Funding

This study was supported by research grant for Young scientists from Medical University of Lodz, Poland, nr. 502-03/5-127-05/502-54-174. It had not been published before. This article is the basis of author’s doctoral thesis.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no that they have no conflict of interest.

References

  1. Aschrafi A, Verheijen JM, Gordebeke PM, Olde Loohuis NF, Menting K, Jager A, Palkovits M, Geenen B, Kos A, Martens GJ, Glennon JC, Kaplan BB, Gaszner B, Kozicz T (2016) MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression. J Psychiatry Neurosci 41(5):342–353CrossRefPubMedPubMedCentralGoogle Scholar
  2. Baulina NM, Kulakova OG, Favorova OO (2016) MicroRNAs: the role in autoimmune inflammation. Acta Nat 8(1):21–33Google Scholar
  3. Bendszus M, Storch-Hagenlocher B (2013) Multiple sclerosis and other demyelinating diseases. In: Hähnel S (ed) Inflammatory diseases of the brain. Springer, Berlin, Heidelberg p. 3–18Google Scholar
  4. Devier DJ, Lovera JF, Lukiw WJ (2015) Increase in NF-κB-sensitive miRNA-146a and miRNA-155 in multiple sclerosis (MS) and pro-inflammatory neurodegeneration. Front Mol Neurosci 8:5CrossRefPubMedPubMedCentralGoogle Scholar
  5. Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S et al (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 10:1252–1259CrossRefPubMedGoogle Scholar
  6. Dugas JC, Cuellar TL, Scholze A, Ason B, Ibrahim A, Emery B et al (2010) Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination. Neuron 65:597–611CrossRefPubMedPubMedCentralGoogle Scholar
  7. Dwivedi Y (2011) Evidence demonstrating role of microRNAs in the etiopathology of major depression. J Chem Neuroanat 42:142–156CrossRefPubMedPubMedCentralGoogle Scholar
  8. Faria O, Moore CS, Kennedy TE, Antel JP, Bar-Or A, Dhaunchak AS (2012) MicroRNA dysregulation in multiple sclerosis. Front Genet 3:311Google Scholar
  9. Fenoglio C, Cantoni C, de Riz M, Ridolfi E, Cortini F, Serpente M, Villa C, Comi C, Monaco F, Mellesi L, Valzelli S, Bresolin N, Galimberti D, Scarpini E (2011) Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis. Neurosci Lett 504:9–12CrossRefPubMedGoogle Scholar
  10. Fenoglio C, Ridolfi E, Galimberti D, Scarpini E (2012) MicroRNAs as active players in the pathogenesis of multiple sclerosis. Int J Mol Sci 13(10):13227–13239CrossRefPubMedPubMedCentralGoogle Scholar
  11. Freiesleben S, Hecker M, Zettl UK, Fuellen G, Taher L (2016) Analysis of microRNA and gene expression profiles in multiple sclerosis: integrating interaction data to uncover regulatory mechanisms. Sci Rep 6.  https://doi.org/10.1038/srep34512
  12. Gandhi R, Healy B, Gholipour T et al (2013) Circulating microRNAs as biomarkers for disease staging in multiple sclerosis. Ann Neurol 73(6):729–740CrossRefPubMedGoogle Scholar
  13. Grasso M, Piscopo P, Confaloni A, Denti MA (2014) Circulating miRNAs as biomarkers for neurodegenerative disorders. Molecules 19:6891–6910CrossRefPubMedGoogle Scholar
  14. Huang L, Liu Y, Wang L, Chen R, Ge W, Lin Z, Zhang Y, Liu S, Shan Y, Lin Q, Jiang M (2013) Down-regulation of miR-301a suppresses pro-inflammatory cytokines in Toll-like receptor-triggered macrophages. Immunology 140(3):314–322PubMedPubMedCentralGoogle Scholar
  15. Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R et al (2009) MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain 132:3342–3352CrossRefPubMedGoogle Scholar
  16. Kacperska MJ, Jastrzębski K, Tomasik B, Walenczak J, Konarska-Król M, Glabinski A (2015) Selected extracellular microRNA as potential biomarkers of multiple sclerosis activity—preliminary study. J Mol Neurosci 56:154–163CrossRefPubMedGoogle Scholar
  17. Kim J, Krichevsky A, Grad Y et al (2004) Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci U S A 101:360–365CrossRefPubMedGoogle Scholar
  18. Liu X, Leung S, Wang C, Tan Z, Wang J, Guo TB, Fang L, Zhao Y, Wan B, Qin X, Lu L, Li R, Pan H, Song M, Liu A, Hong J, Lu H, Zhang JZ (2010) Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease. Nat Med 16(2):191–197CrossRefPubMedGoogle Scholar
  19. Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) advisory committee on clinical trials of new agents in multiple sclerosis. Neurology 46(4):907–911CrossRefPubMedGoogle Scholar
  20. Ma X, Zhou J, Zhong Y, Jiang L, Mu P, Li Y, Singh N, Nagarkatti M, Nagarkatti P (2014) Expression, regulation and function of MicroRNAs in multiple sclerosis. Int J Med Sci 11(8):810–818CrossRefPubMedPubMedCentralGoogle Scholar
  21. Moore CS, Rao VT, Durafourt BA, Bedell BJ, Ludwin SK, Bar-Or A, Antel JP (2013) miR-155 as a multiple sclerosis-relevant regulator of myeloid cell polarization. Ann Neurol 74(5):709–720CrossRefPubMedGoogle Scholar
  22. Niwa R, Slack FJ (2007) The evolution of animal microRNA function. Curr Opin Genet Dev 17:145–150CrossRefPubMedGoogle Scholar
  23. O’Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA et al (2010) MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 33:607–619CrossRefPubMedPubMedCentralGoogle Scholar
  24. O’Connell RM, Rao DS, Baltimore D (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30:295–312CrossRefPubMedGoogle Scholar
  25. Paraboschi EM, Solda G, Gemmati D, Orioli E, Zeri G, Benetti MD, Salviati A, Barizzone N, Leone M, Duga S, Asselta R (2011) Genetic association and altered gene expression of Mir-155 in multiple sclerosis patients. Int J Mol Sci 12(12):8695–8712CrossRefPubMedPubMedCentralGoogle Scholar
  26. Siegel SR, Mackenzie J, Chaplin G, Jablonski NG, Griffiths L (2012) Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep 39(5):6219–6225CrossRefPubMedGoogle Scholar
  27. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 4:423–433Google Scholar
  28. Wang K, Zhang S, Weber J, Baxter D, Galas DJ (2010) Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res 38(20):7248–7259Google Scholar
  29. Wu T, Chen G (2016) miRNAs participate in MS pathological processes and its therapeutic response. Mediat Inflamm.  https://doi.org/10.1155/2016/4578230
  30. Zhao X, He X, Han X, Yu Y, Ye F, Chen Y et al (2010) MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65:612–626CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Marta Niwald
    • 1
    • 2
  • Monika Migdalska-Sęk
    • 3
  • Ewa Brzeziańska-Lasota
    • 3
  • Elżbieta Miller
    • 1
    • 2
  1. 1.Department of Physical MedicineMedical University of LodzLodzPoland
  2. 2.Neurorehabilitation Ward, III General Hospital in LodzLodzPoland
  3. 3.Department of Molecular Bases of Medicine, 1st Chair of Internal DiseasesMedical University of LodzLodzPoland

Personalised recommendations