выявление латентной функциональной недостаточности дофаминергических нейронов нигростриатной системы на хронической модели болезни Паркинсона

Сафандеев, В.В.; Угрюмов, М.В.

Авторы: Сафандеев В.В., Угрюмов М.В.
Журнал: Нейрохимия
Том: 34
Номер: 4
Год издания: 2017
Первая страница: 290
Последняя страница: 295
DOI: 10.1134/S1819712417040079
Аннотация: Parkinson's disease (PD) is socially significant disease with a long term (decades) latent period of development, which, despite the efforts of clinicians, leads to disability and lethality. This is due to late diagnosis and the onset of treatment after the death of most nigrostriatal dopaminergic neurons, a key element in the regulation of motor function. The only hope for success is the development of PD diagnostics at the early (preclinical) stage, long before the appearance of motor symptoms, and neuroprotective treatment aimed at slowing the death of neurons. For the first time in psychiatry and neurology, we offered to use a provocative test by means of reversible inhibition of dopamine synthesis with α-methyl-p-tyrosine (αMpT) for the early (preclinical) diagnostics of PD. Besides, we hypothesized that this test can be used not only for early diagnostics of PD, but also for assessing the degree of the degradation of nigrostriatal dopaminergic system at the preclinical stage of PD, which is important for prognosis of the disease development and optimization of therapy. Therefore, the goal of this study was to determine the minimum doses of αMpT in which it causes movement dysfunction in mice at the model of the preclinical stage of PD at various degrees of degradation of the nigrostriatal dopaminergic system. PD was modeled with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), proneurotoxin, in C57Bl/6 mice at the age of 8-9 weeks. When solving the first objective of this study, a minimum dose (75 mg / kg) was selected in which αMpT caused motor symptoms at modeling the early preclinical stage of PD with a 20% reduction in DA in the striatum. At solving the second objective, a minimum dose (50 mg / kg) was found in which αMpT caused motor dysfunction at the model of the late preclinical stage of PD, with a 53% decrease in DA level. Thus, it was shown in this study that the provocative test can be used not only for the early diagnostics of PD, but also for assessment the degree of the degradation of nigrostriatal dopaminergic system at the preclinical stage of PD. The work was supported by the Ministry of Education and science of the Russian Federation research project's № 0108-2018-0006.
Добавил в систему: Сафандеев Виталий Васильевич

	ИСТИНА	Войти в систему Регистрация
	ИПМех РАН
	Главная Поиск Статистика О проекте Помощь

ИСТИНА

ИПМех РАН

выявление латентной функциональной недостаточности дофаминергических нейронов нигростриатной системы на хронической модели болезни Паркинсонастатья