Melatonin Effects in Young and Aging Mice with the Toxic Cuprizone-Induced Demyelination

The following indices were assessed in 3-5-month old and 15-17-month old 129/Sv mice treated with cuprizone and melatonin: the number of activated T-lymphocytes, macrophages, neural stem cells (determined by CD3, Mac1, and nestin markers), structurally unchanged neurons, malondialdehyde (MDA) content, antioxidant enzyme activities in the brain, the blood level of the thymic hormone thymulin, and the behavioral indices. The animals were fed with cuprizone for 3 weeks. From the eighth day of cuprizone treatment, mice were injected with melatonin (1 mg/kg, at 6 p.m. daily). The results demonstrated an increase in the number of CD3, Mac1, and nestin cells and the MDA level and a decrease in the activity of glutathione peroxidase (GP) in the brains of young and aging mice fed with cuprizone. Mice of both age groups demonstrated a decrease in the proportion of unchanged neurons in the central nervous system, the motor and emotional activity, and the muscle tone. Regardless of animal age, melatonin injections led to a decrease in the number of CD3 and Mac1 cells and the MDA level and an increase in GP activity and the thymulin level. The decrease in the number of nestin cells was accompanied by an increase in the number of unchanged neurons. The effects of both neurotoxin and melatonin on the immune factors and the structure and functional state of the neurons were more pronounced in young mice. Thus, the positive effect of melatonin in young and aging mice upon cuprizone-induced demyelination was mainly mediated by pathogenic factors.