title: The Effect of Melatonin on Behavioral, Molecular, and Histopathological Changes in Cuprizone Model of Demyelination.
abstract: Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The protective effects of melatonin (MLT) on various neurodegenerative diseases, including MS, have been suggested. In the present study, we examined the effect of MLT on demyelination, apoptosis, inflammation, and behavioral dysfunctions in the cuprizone toxic model of demyelination. C57BL/6J mice were fed a chaw containing 0.2 % cuprizone for 5 weeks and received two doses of MLT (50 and 100 mg/kg) intraperitoneally for the last 7 days of cuprizone diet. Administration of MLT improved motor behavior deficits induced by cuprizone diet. MLT dose-dependently decreased the mean number of apoptotic cells via decreasing caspase-3 and Bax as well as increasing Bcl-2 levels. In addition, MLT significantly enhanced nuclear factor-κB activation and decreased heme oxygenase-1 level. However, MLT had no effect on interleukin-6 and myelin protein production. Our data revealed that MLT improved neurological deficits and enhanced cell survival but was not able to initiate myelin production in the cuprizone model of demyelination. These findings may be important for the design of potential MLT therapy in demyelinating disorders, such as MS.
authors: Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran.|Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Gelareh
authors: G
authors: Vakilzadeh
authors: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Fariba
authors: F
authors: Khodagholi
authors: Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran.|Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Tahereh
authors: T
authors: Ghadiri
authors: Infectious Diseases Research Center, Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors: Amir
authors: A
authors: Ghaemi
authors: Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Farshid
authors: F
authors: Noorbakhsh
authors: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. msharifzadeh@sina.tums.ac.ir.|Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran. msharifzadeh@sina.tums.ac.ir.
authors: Mohammad
authors: M
authors: Sharifzadeh
authors: Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran. gorjial@uni-muenster.de.|Department of Neurology, Klinik und Poliklinik für Neurochirurgie, Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster, Germany. gorjial@uni-muenster.de.
authors: Ali
authors: A
authors: Gorji
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011897:Random Allocation
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D003471:Cuprizone; D008550:Melatonin
keywords: Cell death; Corpus callosum; Neuroinflammation; Pineal gland; Remyelination