Changes in nigral neuronal structure, indices of antioxidant protection of the brain and behavior in mice of different age with MPTP parkinsonism model

I.F. Labunets, N.A. Utko, S.I. Savosko, T.N. Panteleymonova, G.M. Butenko


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.


neurotoxin MPTP; parkinsonism; nigral neurons; malondialdehyde and antioxidant enzymes of the brain; behavioral reactions


Karaban I.N., Karaban N.V., Karasevych N.V. The ways of neuroprotection in Parkinson’s disease International neurogical journal. 2011. № 6(44). P. 95-99.

Sulzev D., Surmeiter D.J. Neuronal vulnerability, pathogenests and Parkinson’s disease. Mov. Disord. 2013. Vol. 28. P. 715-724. doi: 10.1002/mds.25095.

Zagni E., Simoni L., Colombo D. Sex and gender differences in central nervous system-related disorders. NeuroSci J. 2016. Article ID 2827090. 13 p. http://dx.doi. org/10.1155/2016/2827090.

Guo J.-D., Zhao X., Li Y., Li G.-R., Liu X-L. Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease (Review). Int. J. of molecular medicine. 2018. Vol. 41. P. 1817-1825. doi: 10.3892/ijmm.2018.3406.

Labunets I.F., Talanov S.A., Vasilyev R.G., Rodnichenko A.E., Utko N.A., Kyzminova I.A. et al. Thymic hormones, antioxidant enzymes and neurogenesis in bulbus olfactorius of rats with hemiparkinsonism: effect of melatonin. Int. J. Phys. Pathophys. 2016. Vol. 7. № 4. P. 285-298. DOI: 10.1615/IntJPhysPathophys.v7.i4.10.

Hwang O. Role of oxidative stress in Parkinson’s dise-ase. Exp. Neurobiol. 2013. Vol. 22. № 1. P. 11-17. doi: 10.5607/en.2013.22.1.11.

Gonchar O., Mankovska I., Rozova K., Bratus L., Karaban I. Novel approaches to correction of mitochondrial dysfunction and oxidative disorders in Parkinson’s desease. Fiziol. Zh. 2019. Vol. 65. № 3. P. 61-72.

Zeng X.S., Geng W.Sh., Jia J.J. Neurotoxin-induced animal models of Parkinson disease: pathogenic mechanism and assessment. ASN Neuro. 2018. Vol. 10. P. 1-15. doi: 10.1177/175909/418777438.

Ugrumov M.V., Khaindrava V.G., Kozina E.A., Kkucheryanu V.G., Bocharov E.V., Kryzhanovsky G.N. et al. Modeling of precliniical and clinical stages of Parkinson’s disease in mice. Neuroscience. 2011. Vol. 181. P. 175-188. doi: 10.1016/j.neuroscience.2011.03.007.

Labunets I.F. Possibilities and prospects of the application of the in vivo and in vitro toxic cuprizone model for demyelination in experimental and clinical neurology (literature review and own research results). Ukrai’ns’kiy nevrologichniy zhurnal. Ukrainian Neurological Journal. 2018. № 2. P. 63-68.

Jackson-Lewis V., Przedborski S. Protocol for the MPTP mouse model of Parkinson’s disease. Nature Protocols. 2007. Vol. 2. № 1. P. 141-151. doi: 10.1038/nprot.2006.342.

Franklin K. The mouse brain in stereotaxic coordinates. Gulf Professional Publishing. 2004. 101 р.

Amikishieva A.V. Behavioral phenothyping: up-to date me-thods and equipment. Vestnik VOGiS. 2009. Vol. 13. № 3. Р. 529-542.

Fernagut P.O., Diguet E., Labattu B., Tison F. A simple method to measure stride length as an index of nigrostrial dysfunction in mice. J. Neurosci. Methods. 2002. Vol. 113. № 2. Р. 123-130. DOI: 10.1016/s0165-0270(01)00485-x.

Uchiyama M., Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal. Biochem. 1978. Vol. 86. № 1. P. 271-278. DOI: 10.1016/0003-2697(78)90342-1.

Labunets I.F. Behavioral features in the mice of various strains and sex with model of parkinsonism. Fiziol. Zh. 2020. Vol. 66. № 1. Р. 18-24. ISSN 0201-8489. DOI: ISSN 0201-8489.

Torres E.R., Akinyeke T., Stagaman K., Duvoisin R.M., Meshul Ch.K., Sharpton Th.J. et al. Effects of sub-chronic MPTP exposure on behavioral and cognitive performance and the microbiome of wild-type and mGlu8 knockout female and male mice. Front. Behav. Neurosci. 2018. Vol. 12. Article 140. 15 p. doi: 10.3389/fnbeh.2018.00140. eCollection 2018.

Mathai A., Ma Y., Pare J.-F., Villalba R.M., Wichmann Th., Smith Y. Reduced cortical innervation of the subthalamic nucleus in MPTP-treated parkinsonian monkeys. Brain. 2015. Vol. 138. P. 946-952. doi: 10.1093/brain/awv018.

Meredith G.E., Rademacher D.J. MPTP mouse models of Parkinson’s disease: an update. J. Parkinsons Dis. 2011. Vol. 1. № 1. P. 19-33. doi: 10.3233/JPD-2011-11023.

Huang D., Xu J., Wang J., Tong J., Bai X, Li H. et al. Dynamic changes in the nigrostrial pathway in the MPTP mouse model of Parinson’s disease. Parkinson disease. 2017. Article ID 9349487. 7 p.

Labunets I.F. Changes of thymic endocrine function, brain macrophages and T-lymphocytes in mice of different ages after administration of neurotoxin cuprizone and cytokine. International Neurogical Journal. 2018. № 4(98). Р. 114-120. DOI: 10.22141/2224-0713.4.98.2018.139434.

Freitas H.R., Ferreira G.D.C., Trevenzoli I.H., Oliveira K.J., de Melo Reis R.A. Fatty acids, amtioxidants and physical activity in brain aging. Nutrients. 2017. Vol. 9. № 11. P. E1263. doi: 10.3390/nu9111263.

Guo L., Xiong H., Kim J.-I., Wu Y.-W., Laichandani R.R., Cui Y. et al. Dynamic re-wiring of neural circuits in the motor cortex in mouse models of Parkinson’s disease. Nat. Neurosci. 2015. Vol. 18. № 9. P. 1299-1309. doi: 10.1038/nn.4082.

Mathai A., Ma Y., Pare J.-F., Villalba R.M., Wichmann Th., Smith Y. Reduced cortical innervation of the subthalamic nucleus in MPTP-treated parkinsonian monkeys. Brain. 2015. Vol. 138. P. 946-962. doi: 10.1093/brain/awv018.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2020


   Seo анализ сайта