Abstract
Multiple sclerosis (MS) is a progressive chronic inflammatory autoimmune disease of the myelin sheath, and melatonin is a powerful antioxidant and anti-inflammatory agent. The present study evaluated the protective effect of melatonin on demyelination and remyelination processes in male and female mice with experimental MS induced by cuprizone. This model of experimental MS in mice is widely used because cuprizone administration causes an artificial demyelination reaction through oligodendrocyte apoptosis, while its withdrawal leads to spontaneous remyelination. Male and female SWR/J mice (n = 78) were divided into three main groups (control, cuprizone, and cuprizone + melatonin), which were each further subdivided into males and females. Cuprizone was orally administered at a dose of 400 mg/kg/day by oral gavage for 5 weeks. In addition, melatonin was intraperitoneally administered for 9 weeks at a dose of 80 mg/kg/day. During the demyelination stage, melatonin exhibited a neuroprotective function in both male and female mice. This was evidenced by improved locomotor activity, increased antioxidant levels (catalase, superoxide dismutase, glutathione peroxidase, and glutathione), and reduced levels of malondialdehyde and inflammatory factors (interleukin-1 beta and tumor necrosis factor-alpha) in male and female mice. However, the effect of melatonin during the remyelination stage varied between sexes; male mice experienced protective effects following melatonin administration, whereas no effect was observed in female mice. These results suggest a complex interaction involving exogenous melatonin, remyelination, and endogenous female sex hormones.
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Acknowledgments
The authors would like to extend thanks to Dr. Ayman Abbas and Dr. Umama Abdelsalam (veterinary pathologists, Animal Unit Committee, King Fahad Medical Research Center) and to Professor Najla Alshetani (Faculty of Pharmacology, King Abdul-Aziz University) for their procedural assistance and support. We thank Ryan Chastain-Gross, Ph.D., from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
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This work was financially supported by King Fahad Medical Research Center and King Abdul-Aziz University, Jeddah, SA.
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All animal experiments were conducted according to the guidelines of the animal unit committee at King Fahad Center for Medical Research. The study was designed in agreement with biomedical ethics research committee at King Abdul-Aziz University (Reference No. 613-18).
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Abo Taleb, H.A., Alghamdi, B.S. Neuroprotective Effects of Melatonin during Demyelination and Remyelination Stages in a Mouse Model of Multiple Sclerosis. J Mol Neurosci 70, 386–402 (2020). https://doi.org/10.1007/s12031-019-01425-6
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DOI: https://doi.org/10.1007/s12031-019-01425-6