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Analysis of platelet-derived growth factor receptor A and oligodendrocyte transcription factor 2 markers following Hydroxychloroquine administration in animal induced multiple sclerosis model

Abstract

It has been shown that following demyelination, Oligodendrocyte Progenitor Cells (OPCs) migrate to the lesion site and begin to proliferate, and differentiate. This study aimed to investigate the effects of Hydroxychloroquine (HCQ) on the expression of OLIG-2 and PDGFR-α markers during the myelination process. C57BL/6 mice were fed cuprizone pellets for 5 weeks to induce demyelination and return to a normal diet for 1 week to stimulate remyelination. During the Phase I all of the animals except CPZ and Vehicle groups were exposed to HCQ (2.5, 10, and 100 mg/kg) via drinking water. At the end of the study, animals were euthanized, perfused and the brain samples were assessed for myelination and immunohistochemistry evaluation. What is remarkable is the high rate of Olig2 + cells in the groups treated with 10 and 100 mg/kg HCQ in the demyelination phase and its decreasing trend in the remyelination phase. However, there was no significant difference between groups during phase I and Phase II based on the percentage of olig-2+/total cells in the corpus callosum region. The number of PDGFR-α+ cells in the group treated with 10 mg/kg HCQ was significant in the first phase (p value < 0.05). Considering that the 100 mg/kg HCQ group had the highest level of PDGFR-α as well as the highest level of myelin repair in LFB staining, it could be inferred that it was the most effective dose in inducing proliferation and migration of OPCs.

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Funding

This study was supported by a grant (Project No. 397640) from Isfahan Pharmaceutical Science Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

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Contributions

HAS and MAO conceived of the presented idea, HAS and SME 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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The authors declare that they have no conflict of interest.

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All procedures were approved by the Iran National Committee for Ethics in Biomedical Research (IR.MUI.RESEARCH.REC.1397.451) which was performed in accordance with the Guidelines for the Care and Use of Laboratory Animals.

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Safaei, H.A., Eftekhari, S.M. & Aliomrani, M. Analysis of platelet-derived growth factor receptor A and oligodendrocyte transcription factor 2 markers following Hydroxychloroquine administration in animal induced multiple sclerosis model. Metab Brain Dis 36, 2101–2110 (2021). https://doi.org/10.1007/s11011-021-00802-8

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Keywords

  • Cuprizone
  • Hydroxychloroquine
  • PDGFR-α
  • Olig-2
  • OPC
  • Myelin
  • Immunohistochemistry