Abstract:
:Parkinson's disease (PD) is characterized by the appearance of motor symptoms many years after the onset of neurodegeneration, which explains low efficiency of therapy. Therefore, one of the priorities in neurology is to develop an early diagnosis and preventive treatment of PD, based on knowledge of molecular mechanisms of neurodegeneration and neuroplasticity in the nigrostriatal system. However, due to inability to diagnose PD at preclinical stage, research and development must be performed in animal models by comparing the nigrostriatal system in the models of asymptomatic and early symptomatic stages of PD. In this study, we showed that despite the progressive loss of neurons in the substantia nigra at the presymptomatic and symptomatic stage, almost no change was observed in the main functional characteristics of this brain region, including dopamine (DA) uptake and release, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) expression, and activity of MAO-A and MAO-B. In the striatum of presymptomatic mice, some parameters (DA release and uptake, MAO-A activity) remained compensatory unchanged or compensatory decreased (MAO-B gene expression and activity), while others-a reduction in DA levels in tissue and extracellular space and in VMAT2 and DAT expression-manifest the functional failure. In symptomatic mice, only a few parameters (spontaneous DA release and uptake, MAO-B gene expression and activity) remained at the same level as at presymptomatic stage, while most parameters (DA level in tissue and extracellular space, DA-stimulated release, VMAT2 and DAT contents), decreased, showing decompensation, which was enhanced by increasing MAO-A activity. Thus, this study provides a comprehensive assessment of the molecular mechanisms of neuroplasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine models of preclinical and clinical stages of PD, which could potentially serve as a powerful tool for translational medicine.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
Mingazov ER,Khakimova GR,Kozina EA,Medvedev AE,Buneeva OA,Bazyan AS,Ugrumov MVdoi
10.1007/s12035-017-0559-6subject
Has Abstractpub_date
2018-04-01 00:00:00pages
2991-3006issue
4eissn
0893-7648issn
1559-1182pii
10.1007/s12035-017-0559-6journal_volume
55pub_type
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