Changes in nigral neuronal structure, indices of antioxidant protection of the brain and behavior in mice of different age with MPTP parkinsonism model
Background. Mass death of the nigral dopaminergic neurons of the brain at Parkinson’s disease leads to the appearance of typical motor disorders. The effect of age and oxidative stress in its development is shown. This study aimed at the assessment of the effects of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on changes in the structure of nigral neurons, oxidative stress and antioxidant protection of the brain, as well as the behavior of the mice of various age. Materials and methods. FVB/N and 129/Sv male and female mice aged 6–7 months were injected with MPTP at the dose of 12 mg/kg 4 times every two hours or at the dose of 30 mg/kg once per day. Mice aged 15–16 months were injected once with neurotoxin at a dose of 30 mg/kg.
Results. Four injections (12 mg/kg) and one injection (30 mg/kg) of MPTP resulted in the damage to the structure in 48–60 % and 71–98 % of neurons of the compact part of substatia nigra in adult mice of both strains and sex, respectively. A single injection of MPTP at the dose of 30 mg/kg to aging mice damaged to the structure of about 30 % of the neurons in the compact part of substantia nigra. The results of open field tests, rigidity and the rotarod tests showed that the same dose of neurotoxin resulted in the impairment of motor and non-motor activities and mainly in the motor activity in adult and aging mice, respectively. The content of malondialdehyde significantly increases in the brain of experimental adults and aging mice, while changes in the activity of superoxide dismutase, catalase and glutathione reductase (decrease and increase) depend on the age and strain. Conclusions. There are age-related differences in the effect of MPTP on the structure of nigral neurons, on the activity of antioxidant enzymes in the brain and on the behavior of mice. The results may be useful in studying parkinsonism pathogenesis and developing individua-lized approaches to its therapy.
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