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Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

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Abstract

Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary manipulation to reduce calorie intake which has been shown to improve neuroprotection and attenuate neurodegenerative disorders. Here, we evaluated the effect of 33% CR regimen for 4 weeks on the remyelination capacity of Cuprizone (CPZ) induced demyelination in a mouse model of MS. Results showed that CR induced a significant increase in motor coordination and balance performance in CPZ mice. Also, luxol fast blue (LFB) staining showed that CR regimen significantly improved the remyelination in the corpus callosum of CPZ + CR mice compared to the CPZ group. In addition, CR regimen significantly increased the transcript expression levels of BDNF, Sox2, and Sirt1 in the corpus callosum of CPZ mice, while decreasing the p53 levels. Moreover, CR regimen significantly decreased the apoptosis rate. Furthermore, astrogliosis (GFAP + astrocytes) and microgliosis (Iba-1 + microglia) were significantly decreased by CR regimen while oligodendrogenesis (Olig2+) and Sirt1 + cell expression were significantly increased in the corpus callosum of CPZ + CR mice compared to the CPZ group. In conclusion, CR regimen can promote remyelination potential in a CPZ-demyelinating mouse model of MS by increasing oligodendrocyte generation while decreasing their apoptosis.

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Funding

The current study was supported by a grant (number 96-04‐30‐ 36919) from the Tehran University of Medical Sciences and Health Services, Tehran, Iran.

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Sina Mojaverrostami, Parichehr Pasbakhsh, Saeid Nekoonam, Davood Zarini, Leila Noori, Elham Shiri & Iraj Ragerdi Kashani

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

    Soheila Madadi

  3. Neuroscience Unit, Menoufia Medical School, Shebin El Kom, Egypt

    Mohamad Salama

  4. ER045, PRASE, DSST and Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon

    Kazem Zibara

Authors
  1. Sina Mojaverrostami
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  2. Parichehr Pasbakhsh
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Correspondence to Iraj Ragerdi Kashani.

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This article does not contain any studies with human participants performed by any of the authors. All experiments involving the use of animals were approved by the Institutional Animal Care and Use Committee (IACUC) of the Tehran University of Medical Science. Animals were kept in quarantine for approx. 1 week prior to use. All applicable international, national, and institutional guidelines for the care and use of animals were followed. All animals were kept in standard conditions with unlimited access to food and water. Surgical procedures were performed under deep anesthesia. Housing of animals and experimental procedures were carried out in accordance with the guidelines of the Iranian Agriculture Ministry and of the European Communities Council Directive (86/609/EEC).

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Mojaverrostami, S., Pasbakhsh, P., Madadi, S. et al. Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis. Metab Brain Dis 35, 1211–1224 (2020). https://doi.org/10.1007/s11011-020-00597-0

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