Department of Human and General Physiology, University of Bologna, Piazza di Porta San Donato 2, I-40126, Bologna, Italy.
Rev Neurosci. 2011;22(4):419-55. doi: 10.1515/RNS.2011.037.
Down syndrome (DS) is a genetic pathology caused by the triplication of human chromosome 21. Although individuals with DS have various medical problems, intellectual disability is the most invalidating aspect of the pathology. Despite numerous efforts, the mechanisms whereby gene triplication leads to the DS phenotype have not been elucidated and there are, at present, no therapies to rescue brain developmental alterations and mental disability in individuals with DS. In this review, we focused on the major defects of the DS brain, comparing data regarding humans with DS and mouse models for DS, and therapeutic interventions attempted on animal DS models. Based on the promising results of pharmacotherapies in these models, we believe that it is possible to conclude that tools to improve brain development in DS are now almost at hand. We now know that it is possible to rescue and/or improve neurogenesis, neuron maturation, connectivity, neurodegeneration and behavior. We believe that the knowledge gained in DS mouse models provides a rational basis to start new clinical trials in infants, children and adults with DS, exploiting drugs that have proved able to rescue various facets of the DS neurologic phenotype. It is not unreasonable to consider that the results of these trials may provide a positive answer to the question: 'Is it possible to improve brain development in DS?'.
唐氏综合征（DS）是一种由人类 21 号染色体三体引起的遗传病理学。尽管患有 DS 的个体存在各种医疗问题，但智力障碍是该病理学最具致残性的方面。尽管进行了大量努力，但基因三倍体导致 DS 表型的机制仍未阐明，目前也没有治疗方法可以挽救 DS 患者的大脑发育改变和智力残疾。在这篇综述中，我们重点关注 DS 大脑的主要缺陷，比较了 DS 患者和 DS 小鼠模型的数据，并对动物 DS 模型进行了治疗干预。基于这些模型中药物治疗的有希望的结果，我们相信可以得出结论，目前几乎已经有了改善 DS 大脑发育的工具。我们现在知道，有可能挽救和/或改善神经发生、神经元成熟、连接、神经退行性变和行为。我们相信，在 DS 小鼠模型中获得的知识为在婴儿、儿童和成人 DS 患者中开始新的临床试验提供了合理的基础，利用已证明能够挽救 DS 神经表型各个方面的药物。考虑到这些试验的结果可能会对“是否有可能改善 DS 大脑发育？”这一问题给出积极的答案，这并非不合理。
