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Contents Modeling of Parkinsonism in Mice with MPTP: from Early Presymptomatic to Advanced Symptomatic Stage

Keywords:

M.V. Ugrumov, E.A. Kozina, V.G. Khaindrava, V.G. Kucheryanu, E.V. Bocharov, G.N. Kryzhanovsky, V.S. Kudrin, V.B. Narkevich, P.M. Klodt, K.S. Rayevsky


A degradation of the nigrostriatal dopaminergic system is the key component of pathogenesis of Parkinson’s disease. Initial clinical symptoms appear many years after the onset of neurodegeneration, at a 70% dopamine depletion in the striatum and a 50% loss of nigral dopaminergic neurons. Therefore, the development of preclinical diagnostics and preventive therapy of Parkinson’s disease aiming to shut down or at least to slow down the neurodegenerative process and activation of compensatory processes is an issue of the highest priority. The development of appropriate experimental models of Parkinson’s disease should precede clinical trials. This multidisciplinary study first managed to model in mice with neurotoxin precursor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) all together the following stages of parkinsonism: (a) the early presymptomatic stage manifested by a subthreshold degeneration of axons and dopamine depletion in the striatum without loss of nigral cell bodies; (b) the advanced presymptomatic stage manifested by a subthreshold degeneration of striatal axons and dopamine depletion and by a subthreshold loss of nigral cell bodies; (c) the early symptomatic stage characterized by threshold depletion of striatal dopamine and a loss of dopaminergic axons and nigral cell bodies resulting in motor dysfunction. Compensatory processes were developed in parallel to neurodegeneration that was manifested by the increase of the dopamine content in individual nigral cell bodies and dopamine turnover in the striatum. The developed models might be exploited for: (a) an examination of pathogenetic mechanisms not only in the nigrostriatal system but also in other brain regions and in the periphery; (b) a study of the compensatory mechanisms under dopamine deficiency; (c) a search of precursors of motor disorders and peripheral biomarkers in presymptomatic parkinsonism; (d) the development of preventive therapy aiming to slow down the neurodegeneration and strengthen compensatory processes
References:
May 29, 2020

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