[Melatonin effects in young and aged mice with toxic cuprizone-induced model of demyelination.]

The followings were estimated in the 3-5 and 15-17 months 129/Sv cuprizone- and melatonin-treated mice: the number of activated T-lymphocytes, macrophages, neural stem cells (determined by CD3+, Mac1+ and nestin+ markers), the structurally unchanged neurons, the malondialdehyde (MDA) content and the antioxidant enzyme activities in the brain; the blood thymus hormone thymulin level; and the behavioural indices. The mice were fed with cuprizone for 3 weeks. From the 8th day of the cuprizone treatment the mice were injected with melatonin (1 mg/kg, at 18:00 daily). As a result, the number of the CD3+-, Mac1+-, and nestin+-cells and the MDA content increased while the glutathione peroxidise (GP) activity decreased in the brain of young and aged mice under the influence of cuprizone. In mice of both age groups the proportion of unchanged neurons in the central nervous system, motor and emotional activity and muscle tone were decreased. Regardless of the age of the mice the injections of melatonin decrease the number of СD3+, Мас1+-cells, content of MDA, increase activity of GP and thymulin level. Decrease of the number of nestin+-cells coincides with the growth of the number of unchanged neurons. The effect of both neurotoxin and melatonin on immune factors, the structure and functional state of neurons was more pronounced in young mice. Thus, the positive effect of melatonin in young and aged mice with the cuprizone-induced demyelination was realized mainly through the pathogenetic factors of pathology.