Affiliation:
1. Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia
Abstract
Studying the initial molecular mechanisms of the pathogenesis of Parkinson’s disease (PD), primarily in the nigrostriatal dopaminergic system, is one of the priorities in neurology. Of particular interest is elucidating these mechanisms in the preclinical stage of PD, which lasts decades before diagnosis and is therefore not available for study in patients. Therefore, our main goal was to study the initial molecular mechanisms of the pathogenesis of PD in the striatum, the key center for dopamine regulation in motor function, in a mouse model of the earliest preclinical stage of PD, from 1 to 24 h after the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It was shown that the content of tyrosine hydroxylase (TH), the first enzyme in dopamine synthesis, does not change within 6 h after the administration of MPTP, but decreases after 24 h. In turn, TH activity increases after 1 h, decreases after 3 h, remains at the control level after 6 h, and decreases 24 h after the administration of MPTP. The concentration of dopamine in the striatum gradually decreases after MPTP administration, despite a decrease in its degradation. The identified initial molecular mechanisms of PD pathogenesis are considered as potential targets for the development of preventive neuroprotective treatment.
Funder
The Ministry of Science and Higher Education of the Russian Federation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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