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

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ORIGINAL PAPER

Coenzyme Q10 enhances remyelination and regulate inflammation effects of cuprizone in corpus callosum of chronic model of multiple sclerosis Behnam Khalilian1 · Soheila Madadi2 · Nima Fattahi3 · Beheshteh Abouhamzeh1 Received: 25 June 2020 / Accepted: 17 November 2020 © Springer Nature B.V. 2020

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 lipidsoluble 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. Keywords  Coenzyme Q10 · Cuprizone · Multiple sclerosis · Remyelination · Oxidative stress

Introduction Multiple sclerosis (MS) is a chronic, progressive demyelinating disorder of the central nervous system. The disease affects more than two million people worldwide (Wallin * Beheshteh Abouhamzeh [email protected] 1



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

2



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

3

Non‑communicable Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran



et al. 2019). Unlike most neurodegenerative diseases, unfortunately, the average age of patients with MS is about 30 years and apart from trauma, MS is the leading cau