The effect of exogenous melatonin on behavior and oxidative stress indicators in the brain of aging mice with experimental models of nervous system pathology
Keywords:neurotoxins MPTP and cuprizone, parkinsonism, demyelination, melatonin, aging, malondialdehyde and antioxidant enzymes in the brain, behavioral reactions
Background. There is a connection between impaired functioning of the nervous system and oxidative stress in Parkinson’s disease and multiple sclerosis. The influence of age on the development of these pathologies was shown, as well as the antioxidant properties of the hormone melatonin. The purpose was to investigate the effect of melatonin administration on the behavior, factors of oxidative stress and antioxidant protection in the brain of aging mice with experimental models of parkinsonism and demyelination. Materials and methods. 129/Sv mice aged 15–16 months received neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 30 mg/kg once, or cuprizone daily with food for 3 weeks. Melatonin was administered at a dose of 1 mg/kg daily at 6 p.m. starting from day 7–8 of toxin exposure. The content of malondialdehyde, the activity of antioxidant enzymes in the brain and behavior parameters were assessed in the open field tests for rigidity and in the rotarod test. Results. The locomotor, emotional and exploratory activities in mice with parkinsonism and demyelination models are lower than those in intact animals. Muscle tone decreases under the influence of cuprizone and increases after MPTP injection; the step length decreases in parkinsonism. Melatonin treatment resulted in increasing the number of squares, step length, and decreasing the retention time on a rotating cylinder in mice with parkinsonism and increasing the number of squares, rea-ring and number of boluses in cuprizone-treated mice. Exogenous melatonin reduces the level of brain malondialdehyde increased by neurotoxins and increases the reduced activity of superoxide dismutase and catalase in mice with parkinsonism, catalase and glutathione peroxidase in mice with demyelination. Conclusions. The positive effects of melatonin on the behavior of aging mice with the MPTP parkinsonism model and the cuprizone model of demyeli-
nation are mediated by increased antioxidant protection in the brain.
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