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Modeling of the presymptomatic stage of parkinsonism in mice: Analysis of dopamine release in the striatum

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Abstract

We revised our hypothesis that the absence of motor behavior impairments at the presymptomatic stage of Parkinsonism, when degeneration of nigrostriatal dopaminergic neurons has already occurred, is the result of compensatory maintenance of a normal extracellular dopamine (DA) concentration in the striatum. We used microdialysis to measure extracellular levels of DA, its precursor L-dihydroxyphenylalanine (L-DOPA), and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mouse striatum in a model of the presymptomatic stage of Parkinsonism. This stage was induced by a single subcutaneous injection of the neurotoxin precursor 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP) at a dose of 12 mg/kg. At 14 days after MPTP injection, the extracellular DA content substantially decreased as compared to the control; however, it did not result in alterations of motor behavior, probably due to compensatory processes directed, not to the maintenance of extracellular DA at the normal level, but rather to the elevation of neuronal sensitivity to DA. The extracellular L-DOPA content remained at the normal level. We did not find any changes in the DOPAC and HVA contents.

Thus, degeneration of DA-ergic striatal axons at the presymtomatic stage of Parkinsonism is associated with a decrease in the DA content in the extracellular space. This indicates that activated compensatory mechanisms are not related to the maintenance of DA concentration in the extracellular space but rather to the increased sensitivity of target neurons to DA.

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Correspondence to A. S. Bazya.

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Original Russian Text © Yu.S. Ukraintseva, N.V. Shchegolevskii, V. A. Korshunov, V.G. Kucheryanu, M.V. Ugryumov, A.S. Bazyan, 2010, published in Neirokhimiya, 2010, Vol. 27, No. 2, pp. 164–169.

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Ukraintseva, Y.S., Shchegolevskii, N.V., Korshunov, V.A. et al. Modeling of the presymptomatic stage of parkinsonism in mice: Analysis of dopamine release in the striatum. Neurochem. J. 4, 142–147 (2010). https://doi.org/10.1134/S1819712410020108

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