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 (a toxin that kills myelin forming cells) for 5 weeks which caused severe demyelination of the corpus callosum (CC. The nerve information highway between the left and right sides of the brain). Animals were simultaneously treated with melatonin by daily intra-peritoneal injections. Melatonin exposure reversed (This means it is demyelination was there and the drug turns back the problem, but as they were treating which demyelinating did it stop the demyelination?) cuprizone-induced demyelination and axon protection. Transmission electron microscopy demonstrated significantly increased mitochondrial (cells energy factories) numbers and slightly increased mitochondrial size within CC axons after cuprizone exposure. Melatonin antagonized (blocked) 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. Biochemical analysis showed that oxidative stress (damaging conditions) 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, used in energy production.
There could be good news
Kang JC, Ahn M, Kim YS, Moon C, Lee Y, Wie MB, Lee YJ, Shin T. Melatonin ameliorates autoimmune encephalomyelitis through suppression of intercellular adhesion molecule-1. J Vet Sci. 2001;2(2):85-9.
But there could be bad news
Luzindole, a melatonin receptor antagonist, suppresses experimental autoimmune encephalomyelitis.Constantinescu CS, Hilliard B, Ventura E, Rostami A. Pathobiology. 1997;65(4):190-4.
Melatonin has immune-enhancing effects and can exacerbate autoimmunity. Pinealectomy or light exposure, which suppress melatonin, inhibit T cell autoimmunity. To investigate the involvement of melatonin in experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune demyelinating disease, we tested the effect of luzindole (blocker of melatonin), a melatonin receptor antagonist, on EAE. Luzindole-treated mice did not develop EAE after immunization with spinal cord homogenate, whereas control mice developed EAE. This study suggests that pharmacological inhibition of the immunoenhancing effects of melatonin may prevent autoimmune demyelination.