Degeneration of nigrostriatal dopaminergic neurons in an experimental model of the early clinical stage of Parkinson’s disease

Autor: A. A. Kolacheva, E. A. Kozina, M. V. Ugryumov, Volina Ev
Rok vydání: 2014
Předmět:
Zdroj: Neurochemical Journal. 8:184-192
ISSN: 1819-7132
1819-7124
DOI: 10.1134/s1819712414030076
Popis: The basis of the pathogenesis of Parkinson’s disease (PD) is progressive degeneration of dopaminergic neurons in the nigrostriatal system of the brain. The most important treatment of PD is using of drugs that delay neuronal death. The aim of the present study was to adapt our model of the early clinical stage of PD in mice [1] for its use as a test system for trials of potential neuroprotectors. Our data show that degeneration of the bodies of dopaminergic neurons in the substantia nigra starts 3 h after the last injection of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) whereas the number of dopaminergic axons in the striatum is significantly decreased by this time point. Degradation of axons and neuronal bodies continues for the next 3 h. This period of time appears to be more appropriate for testing of neuroprotectors because later the number of neuronal bodies in the substantia nigra and axons in the striatum do not change. For the development of the test system, it is important to evaluate the functional state of surviving neurons. We found that 3 h after the last MPTP injection, the dopamine (DA) content in the substantia nigra decreased to 25% of the control level and 24 h later the DA content increased again and was 70% of the control value. The tyrosine hydroxylase content in neuronal bodies was similar to the control during the entire period of the study. In the striatum, the DA level decreased to 90% 3 h after the last MPTP injection and remained unchanged by the end of the study; however, the content of tyrosine hydroxylase decreased gradually by 12 h after the injection. Our data probably show the compensatory activation of tyrosine hydroxylase in both the substantia nigra and striatum. Thus, in a mouse model of the early clinical stage of PD we revealed that degeneration of nigrostriatal dopaminergic neurons ends 14 h after the start of the action of the specific neurotoxin. This was accompanied by activation of compensatory processes, which enhance DA-ergic neurotransmission.
Databáze: OpenAIRE
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