Rozhkova I N, Okotrub S V, Brusentsev E Yu, Rakhmanova T A, Lebedeva D A, Kozeneva V S, Shavshaeva N A, Khotskin N V, Amstislavsky S Ya
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2024 Nov;28(7):744-751. doi: 10.18699/vjgb-24-82.
Parkinson's disease (PD) is an age-related neurodegenerative pathology of the central nervous system. The well-known abnormalities characteristic of PD are dysfunctions in the nigrostriatal system including the substantia nigra of the midbrain and the striatum. Moreover, in PD persons, alpha-synucleinopathy is associated with abnormalities in the dopaminergic brain system. To study the mechanisms of this pathology, genetic models in mice have been designed. Transgenic mice of the B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J strain (referred to as B6.Cg-Tg further in the text) possess the A53T mutation in the human alpha-synuclein SNCA gene. The density of neurons in the prefrontal cortex, hippocampus, substantia nigra and striatum in B6.Cg-Tg mice was assessed in our previous work, but the dopaminergic system was not studied there, although it plays a key role in the development of PD. The aim of the current study was to investigate motor coordination and body balance, as well as dopaminergic neuronal density and alpha-synuclein accumulation in the substantia nigra in male B6.Cg-Tg mice at the age of six months. Wild-type mice of the same sex and age, siblings of the B6.Cg-Tg mice from the same litters, lacking the SNCA gene with the A53T mutation, but expressing murine alpha-synuclein, were used as controls (referred to as the wild type further in the text). Motor coordination and body balance were assessed with the rota-rod test; the density of dopaminergic neurons and accumulation of alpha-synuclein in the substantia nigra were evaluated by the immunohistochemical method. There was no difference between B6.Cg-Tg mice and WT siblings in motor coordination and body balance. However, accumulation of alpha-synuclein and a decrease in the number of dopaminergic neurons in the substantia nigra were found in the B6.Cg-Tg mouse strain. Thus, the mice of the B6.Cg-Tg strain at the age of six months have some symptoms of the onset of PD, such as the accumulation of mutant alpha-synuclein and a decrease in the number of dopaminergic neurons in the substantia nigra. Taken together, the results obtained in our work qualify the B6.Cg-Tg strain as a pertinent model for studying the early stage of human PD already at the age of six months.
帕金森病（PD）是一种与年龄相关的中枢神经系统神经退行性病变。PD的典型异常是黑质纹状体系统功能障碍，包括中脑黑质和纹状体。此外，在帕金森病患者中，α-突触核蛋白病与多巴胺能脑系统异常有关。为了研究这种病变的机制，已经设计了小鼠遗传模型。B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J品系的转基因小鼠（文中进一步简称为B6.Cg-Tg）在人类α-突触核蛋白SNCA基因中存在A53T突变。在我们之前的工作中评估了B6.Cg-Tg小鼠前额叶皮质、海马体、黑质和纹状体中的神经元密度，但未对多巴胺能系统进行研究，尽管其在帕金森病的发展中起关键作用。本研究的目的是调查6月龄雄性B6.Cg-Tg小鼠的运动协调性和身体平衡，以及黑质中多巴胺能神经元密度和α-突触核蛋白的积累情况。将相同性别和年龄的野生型小鼠，即来自同一窝的B6.Cg-Tg小鼠的同胞，作为对照（文中进一步简称为野生型），它们缺乏带有A53T突变的SNCA基因，但表达小鼠α-突触核蛋白。通过转棒试验评估运动协调性和身体平衡；采用免疫组织化学方法评估黑质中多巴胺能神经元的密度和α-突触核蛋白的积累情况。B6.Cg-Tg小鼠和野生型同胞在运动协调性和身体平衡方面没有差异。然而，在B6.Cg-Tg小鼠品系中发现黑质中α-突触核蛋白的积累以及多巴胺能神经元数量的减少。因此，6月龄的B6.Cg-Tg品系小鼠出现了一些帕金森病发病的症状，如突变型α-突触核蛋白的积累和黑质中多巴胺能神经元数量的减少。综上所述，我们工作中获得的结果使B6.Cg-Tg品系成为一个在6月龄时就可用于研究人类帕金森病早期阶段的相关模型。
