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Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression

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Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5‐6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin‐ (neurological score = 6) vs PBS‐treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN‐γ, in comparison to PBS‐treated EAE rats whereas no considerable change in IL‐4 levels were found, although they were significantly lower than those of controls. The ratio of IFN‐γ/IL‐4, an indicator of Th‐1/Th‐2, was significantly higher in PBS‐ and melatonin‐ treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP‐deficient areas) in the lumbar spinal cord of melatonin‐treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN‐γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations.
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Keywords: IFN‐γ; astrocytes; cytokine; experimental autoimmune encephalomyelitis; lactate; melatonin; multiple sclerosis

Document Type: Research Article

Publication date: January 1, 2017

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