Морфометрический анализ дофаминергических нейронов черной субстанции головного мозга мышей с генетическим нокаутом альфа-синуклеина при МФТП-индуцированном паркинсонизме

V. V. Goloborshcheva; N. A. Voronina; R. K. Ovchinnikov; V. G. Kucheryanu; S. G. Morozov

doi:10.25557/2310-0435.2021.03.32-37

V. V. Goloborshcheva Institute of General Pathology and Pathophysiology, Moscow, Russia http://orcid.org/0000-0003-2540-4303
N. A. Voronina Institute of General Pathology and Pathophysiology, Moscow, Russia http://orcid.org/0000-0002-1764-6444
R. K. Ovchinnikov Institute of Physiologically Active Substances of the Russian Academy of Sciences, Chernogolovka of Moscow region, Russia; N.I. Pirogov Russian National Research Medical University, Moscow, Russia
V. G. Kucheryanu Institute of General Pathology and Pathophysiology, Moscow, Russia http://orcid.org/0000-0002-5071-3581
S. G. Morozov Institute of General Pathology and Pathophysiology, Moscow, Russia http://orcid.org/0000-0001-5822-5729

DOI: https://doi.org/10.25557/2310-0435.2021.03.32-37

Keywords: Parkinson’s disease, neurodegeneration, genetically modified mice, synucleins, MPTP, dopaminergic neurons

Abstract

The aim of this study was to assess survival of mature dopaminergic (DAergic) neuronal population in the substantia nigra pars compacta (SNpc) of two alpha-synuclein knockout mice strains (Abel-KO and ΔFlox-KO) and of non-synuclein animals (abg-KO) in MPTP-induced parkinsonism.
Material and methods: MPTP water solution was administered to 3-month-old mice intraperitoneally (30 mg/kg daily for 5 days) according to a subchronic protocol. On the 21st day after the last MPTP injection, the brain was excised, fixed in cold Carnoy’s solution and paraffined for the subsequent preparation of histological samples on a Leica RM2265 rotary microtome (Leica Biosystems, Germany). Immunohistochemical staining was performed with antibodies against tyrosine hydroxylase (mouse monoclonal antibodies, Sigma, dilution 1:2000). A comparative morphometric analysis of substantia nigra dopaminergic neurons was performed using the Abercrombie correction.

Results: MPTP-treated alpha-synuclein deficient mice were resistant to the loss of DAergic neurons in the SNpc. Genetic deletion of all three synucleins restored the sensitivity of SNpc DAergic neurons to the MPTP toxicity, which did not differ from the sensitivity of wild type animals.
Conclusion: Based on the morphometric analysis, it was assumed that the specific features of MPTP sensitivity in alpha-synuclein knockout mice are due to an increased functional activity (substitution) of beta-synuclein, which optimizes the capture of DA by synaptic vesicles.

Morphometric analysis of dopaminergic neurons (substantia nigra) in the brain of MPTP-treated alpha-synuclein knockout mice

Abstract