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Microglia polarization by methylprednizolone acetate accelerates cuprizone induced demyelination

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Abstract

Glucocorticoids (GC) are known as inflammatory drugs, which are used in neuroinflammatory diseases. Unlike the classic picture, recent studies have revealed that some GC drugs exacerbate inflammatory responses in their acute and prolonged administration. Multiple sclerosis (MS) is a demyelinating inflammatory disorder, in which reactive M1 microglia phenotype play a central role. Since methylprednisolone (MP), as a synthetic GC, are commonly used by MS patients, in this study, we evaluated the effect of long-term administration of MP on microglia polarization in cuprizone (CPZ)-induced MS model. The immunostaining results showed that chronic exposure to MP in the CPZ treated mice increased the number of Iba-1 positive microglia, which significantly expressed IP10 as M1 marker than arginase as M2 marker. MP treatment induced significant amplification in the transcript levels of iNOS and TNF-α (M1-related markers) in the corpus callosum of the MS mice, whereas no change detected in the expression of IL-10 (M2-related marker) between the groups. In addition, evaluation of myelin by luxol fast blue staining and transmission electron microscopy revealed that prolonged MP administration increased demyelination in comparison to the CPZ group. In conclusion, our results show that chronic MP therapy in the CPZ-induced demyelination model of MS polarized microglia to M1 pro-inflammatory phenotype.

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Acknowledgements

International Campus, Tehran University of Medical Science supported this work and the results described in this paper is part of the student thesis for an M.Sc. degree that was supported by Grant 96-02-103-34934.

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Authors and Affiliations

  1. School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran

    Golaleh Noorzehi

  2. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Poursina Street, 1417613151, Tehran, Iran

    Parichehr Pasbakhsh, Maryam Borhani-Haghighi, Iraj Ragerdi Kashani, Soheila Madadi, Fatemeh Tahmasebi, Saied Nekoonam & Maryam Azizi

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  1. Golaleh Noorzehi
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  2. Parichehr Pasbakhsh
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  3. Maryam Borhani-Haghighi
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Correspondence to Iraj Ragerdi Kashani.

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Noorzehi, G., Pasbakhsh, P., Borhani-Haghighi, M. et al. Microglia polarization by methylprednizolone acetate accelerates cuprizone induced demyelination. J Mol Hist 49, 471–479 (2018). https://doi.org/10.1007/s10735-018-9786-z

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  • DOI: https://doi.org/10.1007/s10735-018-9786-z

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