Abstract
Parkinson’s disease (PD) is one of the most widespread neurodegenerative diseases; it develops as a result of the death of dopaminergic (DA-ergic) neurons of the nigrostriatal system of the brain. It has been shown in autopsy material that the neurodegenerative process spreads to other populations of neurons of the peripheral and central nervous system. In PD patients the tuberoinfundibular DA-ergic system (TIDAS) undergoes degradation; however, no experimental models exist that can reproduce the combined degradation of the nitrostriatal system and the TIDAS. In this work, we analyzed the state of the TIDAS during presymptomatic and symptomatic stages of parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These stages of parkinsonism develop as a result of subthreshold and threshold degradation of the nigrostriatal DA-ergic system. To evaluate the morphofunctional state of the TIDAS, we determined: (a) the number of neurons with tyrosine hydroxylase (TH), a key enzyme of DA synthesis; (b) the sizes of the terminals of TH-positive axons; (c) the levels of TH in the neuronal somas and the terminals of axons; and (d) the contents of DA, noradrenaline, and 3,4-dihydroxyphenyl acetic acid. According to the data that was obtained during the presymptomatic stage, for the TIDAS no changes were found in all the measured parameters. During the symptomatic stage, we observed (a) a decrease in DA content by 50%; (b) a decrease in the level of TH protein in axonal terminals and an increase in neuronal somas; and (c) an increase in the turnover of DA by 149% as compared to the control. The data we obtained suggest that the functional activity of the TIDAS was insufficient; this was seen in the form of alterations of DA metabolism, a decrease in the level of synthesis, probably in axonal terminals, and compensatory acceleration of the functional cycle from synthesis to enzymatic degradation. Although no changes in the number of neurons and axons that express TH was found in the TIDAS, the question of organic degradation of the TIDAS in parkinsonism is still open because TH is a marker of not only DA-ergic neurons that degenerate in the presence of neurotoxins but also of non-DA-ergic neurons that are insensitive to neurotoxins. Thus, during experimental modeling of Parkinsonism, we observed at least the metabolic characteristics of TIDAS degradation only at the symptomatic stage of the disease.
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Original Russian Text © E.A. Degtyareva, T.S. Pronina, M.V. Ugryumov, 2012, published in Neirokhimiya, 2012, Vol. 29, No. 4, pp. 311–317.
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Degtyareva, E.A., Pronina, T.S. & Ugryumov, M.V. The state of the tuberoinfundibular dopaminergic system during modeling of parkinsonism in mice. Neurochem. J. 6, 284–290 (2012). https://doi.org/10.1134/S1819712412030051
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DOI: https://doi.org/10.1134/S1819712412030051