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Coenzyme Q10 enhances remyelination and regulate inflammation effects of cuprizone in corpus callosum of chronic model of multiple sclerosis

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Abstract

Multiple Sclerosis (MS) is a chronic, progressive demyelinating disease of the central nervous system that causes the most disability in young people, besides trauma. Coenzyme Q10 (CoQ10)—also known as ubiquinone—is an endogenous lipid-soluble antioxidant in the mitochondrial oxidative respiratory chain which can reduce oxidative stress and inflammation, the processes associated with demyelination in MS. Cuprizone (CPZ) intoxication is a well-established model of inducing MS, best for studying demyelination—remyelination. In this study, we examined for the first time the role of CoQ10 in preventing demyelination and induction of remyelination in the chronic CPZ model of MS. 40 male mice were divided into four groups. 3 group chewed CPZ-containing food for 12 weeks to induce MS. After 4 weeks, one group were treated with CoQ10 (150 mg/kg/day) by daily gavage until the end of the experiment, while CPZ poisoning continued. At the end of 12 weeks, tail suspension test (TST) and open field test (OFT) was taken and animals were sacrificed to assess myelin basic protein (MBP), oligodendrocyte transcription factor-1 (Olig1), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) by real-time polymerase chain reaction (real-time PCR) and total antioxidant capacity (TAC) and superoxide dismutase (SOD) by Elisa test. Luxol fast blue (LFB) staining was used to evaluate histological changes. CoQ10 administration promoted remyelination in histological findings. MBP and Olig-1 expression were increased significantly in CoQ10 treated group compare to the CPZ-intoxicated group. CoQ10 treatment alleviated stress oxidative status induced by CPZ and dramatically suppress inflammatory biomarkers. CPZ ingestion made no significant difference between normal control group and the CPZ-intoxicated group in TST and OFT. CoQ10 can enhance remyelination in the CPZ model and potentially might have same effects in MS patients.

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Acknowledgements

The authors would like to express their gratitude to the School of Medicine, AJA University of Medical Sciences, Tehran, Iran for their support.

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Authors and Affiliations

  1. Department of Anatomical Sciences, Faculty of Medicine, AJA University of Medical Sciences, 1411718541, Tehran, Iran

    Behnam Khalilian & Beheshteh Abouhamzeh

  2. Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

    Soheila Madadi

  3. Non-communicable Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Nima Fattahi

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  1. Behnam Khalilian
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Khalilian, B., Madadi, S., Fattahi, N. et al. Coenzyme Q10 enhances remyelination and regulate inflammation effects of cuprizone in corpus callosum of chronic model of multiple sclerosis. J Mol Histol 52, 125–134 (2021). https://doi.org/10.1007/s10735-020-09929-x

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