Investigation of the myelin recovery and expression changes of miR-219 and miR-155-3p following the administration of hydroxychloroquine in multiple sclerosis-induced model

Introduction and Objectives: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system which causes demyelination and axonal loss. Based on the previous studies hydroxychloroquine (HCQ) has anti-inflammatory properties and can be a good candidate for the treatment of MS. Moreover, recent studies indicated the role of microRNAs as a biomarker in the diagnosis and treatment of MS. This study aimed to investigate the effect of HCQ on the expression of miR-219 and miR-155-3p involved in the myelination process by cuprizone-induced model.Materials & Methods: MS model was induced by the administration of cuprizone pellets for 5 weeks (demyelination phase) following normal feeding for one week (remyelination phase). In this experimental study, forty-six C57BL/6 mice were randomly divided into five groups and kept under circumstances in vivarium of Isfahan University of Medical Sciences, control group received normal food pellets for 5 weeks, cuprizone group received cuprizone pellets for 5 weeks, treated groups of mice that received cuprizone pellets and drinking water containing HCQ in three doses of 2.5, 10 and 100 mg/kg during the demyelination phase. In the sixth week, all groups were given normal food pellets and tap drinking water to initiate the remyelination phase. At the end of each phase, half of the mice in each group were perfused, and their brains were removed. The expression levels of miR-219 and miR-155-3p were evaluated by quantitative Real-Time PCR from the posterior part of the brain.Results: In this study, the reduction of miR-219 expression and increment of miR-155-3p expression was observed in the cuprizone group as compared to the control group (p < 0.001). A significant increment of miR-219 expression and reduction of miR-155-3p expression was observed in the animals treated with 100 mg/kg of HCQ when compared with the control group (p < 0.0001). There is no significant difference between the cuprizone group and the group treated with 2.5 mg/kg of HCQ.Conclusion: Based on the obtained results of this study, HCQ could enhance myelination process by targeting miR-155-3p down-regulation more than miR-219 up-regulation so it could be a suitable candidate to suppress the demyelination during MS.

کلیدواژه ها:

miR-155-3p ، miR-219 ، Hydroxychloroquine ، Multiple sclerosis ، Myelination ، Cuprizone