Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

Protective effects of melatonin against mitochondrial injury in a mouse model of multiple sclerosis

(2014) Protective effects of melatonin against mitochondrial injury in a mouse model of multiple sclerosis. Experimental Brain Research.

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Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Abstract

Multiple sclerosis (MS) is the most prevalent inflammatory demyelinating disease of the central nervous system. Besides other pathophysiological mechanisms, mitochondrial injury is crucially involved in the development and progression of this disease. Mitochondria have been identified as targets for the peptide hormone melatonin. In the present study, we sought to evaluate the impact of oxidative stress on mitochondrial density and enzyme transcription during experimentally induced demyelination and the protective influence of melatonin. Adult male mice were fed with cuprizone for 5 weeks which caused severe demyelination of the corpus callosum (CC). Animals were simultaneously treated with melatonin by daily intra-peritoneal injections. Melatonin exposure reversed cuprizone-induced demyelination and axon protection. Transmission electron microscopy demonstrated significantly increased mitochondrial numbers and slightly increased mitochondrial size within CC axons after cuprizone exposure. Melatonin antagonized these effects and, in addition, induced the expression of subunits of the respiratory chain complex over normal control values reflecting a mechanism to compensate cuprizone-mediated down-regulation of these genes. Similarly, melatonin modulated gene expression of mitochondrial fusion and fission proteins. Biochemical analysis showed that oxidative stress induced by cuprizone was regulated by melatonin. The data implicate that melatonin abolishes destructive cuprizone effects in the CC by decreasing oxidative stress, restoring mitochondrial respiratory enzyme activity and fusion and fission processes as well as decreasing intra-axonal mitochondria accumulation. © 2014 Springer-Verlag.

Item Type: Article
Keywords: cuprizone; cytochrome c oxidase; hypoxanthine phosphoribosyltransferase; melatonin; mitochondrial enzyme; mitochondrial protein; proton transporting adenosine triphosphate synthase; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone); ubiquinol cytochrome c reductase; antioxidant; cyclooxygenase 2; glutathione; melatonin; monoamine oxidase inhibitor; mt-Atp6 protein, mouse; oxidoreductase; proteolipid protein; proton transporting adenosine triphosphate synthase; Ptgs2 protein, mouse; ubiquinol oxidase, adult; animal cell; animal experiment; animal model; animal tissue; article; brain mitochondrion; cell count; cell density; controlled study; corpus callosum; demyelination; disorders of mitochondrial functions; down regulation; enzyme activity; gene expression regulation; genetic transcription; male; mitochondrial density; mitochondrial respiration; mitochondrial volume; mouse; multiple sclerosis; nerve fiber; neuroprotection; nonhuman; oxidative stress; polymerase chain reaction; priority journal; transmission electron microscopy; treatment outcome; animal; C57BL mouse; chemically induced; disease model; drug effects; genetics; lipid peroxidation; metabolism; mitochondrion; multiple sclerosis; oxidative stress; pathology; ultrastructure, Animals; Antioxidants; Cuprizone; Cyclooxygenase 2; Disease Models, Animal; Gene Expression Regulation; Glutathione; Lipid Peroxidation; Male; Melatonin; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Mitochondria; Mitochondrial Proton-Translocating ATPases; Monoamine Oxidase Inhibitors; Multiple Sclerosis; Myelin Proteolipid Protein; Oxidative Stress; Oxidoreductases
Page Range: pp. 2835-2846
Journal or Publication Title: Experimental Brain Research
Volume: 232
Number: 9
Publisher: Springer Verlag
Identification Number: 10.1007/s00221-014-3946-5
ISSN: 00144819
Depositing User: مهندس جمال محمودپور
URI: http://eprints.muk.ac.ir/id/eprint/1074

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