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Spasticity Treatment Ameliorates the Efficacy of Melatonin Therapy in Experimental Autoimmune Encephalomyelitis (EAE) Mouse Model of Multiple Sclerosis

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Abstract

Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease in the central nervous system (CNS). Melatonin is an effective treatment in MS patients and experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Melatonin secretion peaks at 2 AM, concomitant with the time at which the muscles are resting and the body is exerting its antioxidant activity. The current study was designed to investigate combination treatment of baclofen, a muscle relaxant drug, and melatonin in EAE mice. Results showed that melatonin (Mel) alone or in combination with baclofen (Bac + Mel) reduced clinical scores and demyelination by significantly increasing myelin oligodendrocyte glycoprotein (MOG) levels, a marker for mature oligodendrocytes, compared to EAE mice. Moreover, Mel or Bac + Mel therapy caused a significant increase in IL-4 serum levels, an anti-inflammatory cytokine, whereas IFN-γ serum levels, a pro-inflammatory cytokine, were significantly reduced. On the other hand, Mel or Bac + Mel caused a significant reduction in malondialdehyde (MDA) levels, a marker of oxidative stress, in comparison to EAE mice. In contrast, the activity of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) was significantly increased in Mel and Bac + Mel groups. In summary, combination therapy improved clinical scores and tend to enhance the efficiency of melatonin treatment by further promoting remyelination, decreasing inflammation, and stimulating the activity of antioxidant enzymes, which suggests that prior spasticity treatment increases the efficacy of melatonin therapy in EAE mouse model of MS. Further experimental and clinical studies are needed to ensure the beneficial role of this combination strategy.

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Acknowledgements

This work was supported by a grant from Cell and Molecular Research Center of Yasuj University of Medical Science, Yasuj, Iran.

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Author notes

  1. Majid Ghareghani and Kazem Zibara have contributed equally to this work.

Authors and Affiliations

  1. Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

    Majid Ghareghani & Hossein Sadeghi

  2. CERVO Brain Research Center, Quebec City, QC, G1J 2G3, Canada

    Majid Ghareghani

  3. ER045, Laboratory of Stem Cells, PRASE, Biology Department, Faculty of Sciences, Lebanese University, Beirut, Lebanon

    Kazem Zibara

  4. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

    Naser Farhadi

Authors
  1. Majid Ghareghani
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  2. Kazem Zibara
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  3. Hossein Sadeghi
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  4. Naser Farhadi
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Contributions

MG, KZ, and NF designed the study, collected data, and interpreted results. MG and KZ wrote the paper. HS participated in the collection and interpretation of some data.

Corresponding author

Correspondence to Naser Farhadi.

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Ghareghani, M., Zibara, K., Sadeghi, H. et al. Spasticity Treatment Ameliorates the Efficacy of Melatonin Therapy in Experimental Autoimmune Encephalomyelitis (EAE) Mouse Model of Multiple Sclerosis. Cell Mol Neurobiol 38, 1145–1151 (2018). https://doi.org/10.1007/s10571-018-0580-y

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  • DOI: https://doi.org/10.1007/s10571-018-0580-y

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