Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, Strada Le Grazie 8, I-37134 Verona, Italy.
Cells. 2023 May 27;12(11):1488. doi: 10.3390/cells12111488.
Down syndrome (DS) is a genetically-based disease based on the trisomy of chromosome 21 (Hsa21). DS is characterized by intellectual disability in association with several pathological traits among which early aging and altered motor coordination are prominent. Physical training or passive exercise were found to be useful in counteracting motor impairment in DS subjects. In this study we used the Ts65Dn mouse, a widely accepted animal model of DS, to investigate the ultrastructural architecture of the medullary motor neuron cell nucleus taken as marker of the cell functional state. Using transmission electron microscopy, ultrastructural morphometry, and immunocytochemistry we carried out a detailed investigation of possible trisomy-related alteration(s) of nuclear constituents, which are known to vary their amount and distribution as a function of nuclear activity, as well as the effect of adapted physical training upon them. Results demonstrated that trisomy per se affects nuclear constituents to a limited extent; however, adapted physical training is able to chronically stimulate pre-mRNA transcription and processing activity in motor neuron nuclei of trisomic mice, although to a lesser extent than in their euploid mates. These findings are a step towards understanding the mechanisms underlying the positive effect of physical activity in DS.
唐氏综合征（DS）是一种基于 21 号染色体三体（Hsa21）的遗传性疾病。DS 的特征是智力障碍，同时伴有多种病理特征，其中包括早期衰老和运动协调能力改变。已经发现体育锻炼或被动运动对于改善 DS 患者的运动障碍是有用的。在这项研究中，我们使用了 Ts65Dn 小鼠，这是一种广泛接受的 DS 动物模型，来研究作为细胞功能状态标志物的髓质运动神经元细胞核的超微结构。通过透射电子显微镜、超微结构形态计量学和免疫细胞化学，我们对核成分的可能三体相关改变进行了详细的研究，已知这些改变会随着核活性的变化而改变其数量和分布，以及适应的体育锻炼对它们的影响。结果表明，三体本身对核成分的影响有限；然而，适应的体育锻炼能够长期刺激运动神经元细胞核中转录前 RNA 的转录和加工活性，尽管其程度低于其正常二倍体同伴。这些发现是理解体育活动对 DS 产生积极影响的机制的一个步骤。
