RETRACTED ARTICLE: Protective effects of melatonin against mitochondrial injury in a mouse model of multiple sclerosis

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.

Melatonin Redox Activity. Its Potential Clinical Applications in Neurodegenerative Disorders

“…Melatonin abolishes destructive cuprizone effects in the corpus callosum by decreasing oxidative stress, restoring mitochondrial respiratory enzyme activity and fusion and fission processes as well as decreasing intra-axonal mitochondria accumulation. Protective effects of melatonin against mitochondrial injury in a mouse model of MS were observed [63]. Bahamonde et al showed on the group of 18 MS patients that natalizumab significantly increases melatonin concentration and reduces oxidative stress biomarkers in perpherial blood [64].…”

“…Axonal loss is the main reason of disability progression in MS [59][60][61]. Patients with secondary progressive multiple sclerosis (SPMS) had lower activity of SOD [62,63]. Recent studies pointed out that melatonin genes pathway seems to be involved in MS progression.…”

Melatonin, mitochondria, and Ca2+ homeostasis in the exocrine pancreas: an overview

“…The level of oxidative stress-related markers of mitochondrial apoptosis (Bax, cleaved caspase-3, and PARP, cytochrome c release into the cytosol) decreased in the presence of melatonin in acute respiratory distress syndrome (Sun et al, 2015). Melatonin abolished destructive demyelination effects induced by the drug cuprizone in the corpus callosum, by decreasing oxidative stress and by restoring mitochondrial respiratory enzyme activity and fusion and fission processes (Kashani et al, 2014). Melatonin administration also reduced Bax translocation to the mitochondria and the release of cytochrome c into the cytosol, preventing brain injury following a subarachnoid hemorrhage (Chen et al, 2014).…”

Established and Future Promising Fertility Preservation Options in Adolescence and Adults

“…Some studies have shown that cancer patients have a reduced fertility potential even before starting treatment (17)(18)(19)(20). For this kind of infertility, some reasons have been proposed: primary or secondary hormonal imbalance; anatomic changes (retrograde ejaculation); damage to supporting cells or germinal stem cells; reduction of sperm DNA integrity, numbers, and mo-tility; and a decrease in pituitary gonadotropin levels, all of which can negatively affect fertility (11,12,21,22).…”