title: Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression.
abstract: 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.
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghareghani
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Dokoohaki
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghanbari
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Farhadi
authors.affiliation: ER045, Laboratory of Stem Cells, EDST, Biology Department, Faculty of Sciences, Lebanese University, Beirut, Lebanon.
authors.forename: Kazem
authors.initials: K
authors.lastname: Zibara
authors.affiliation: Department of Chemistry, Behbahan Khatam Alanbia University of Technology, Behbahan, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Khodadoust
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Parishani
authors.affiliation: Cellular and Molecular Gerash Research center, Gerash University of Medical Science, Gerash, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghavamizadeh
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran.
authors.forename: Heibatollah
authors.initials: H
authors.lastname: Sadeghi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood* / Q000139:chemically induced; D005260:Female; D019344:Lactic Acid / Q000097:blood*; D008550:Melatonin / Q000097:blood* / Q000633:toxicity*; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D015415:Biomarkers; D019344:Lactic Acid; D008550:Melatonin
keywords: IFN-γ; astrocytes; cytokine; experimental autoimmune encephalomyelitis; lactate; melatonin; multiple sclerosis