Department of Anatomy, Physiology, and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Neural Plast. 2012;2012:101542. doi: 10.1155/2012/101542. Epub 2012 Jul 12.
Down syndrome (DS) is caused by the overexpression of genes on triplicated regions of human chromosome 21 (Hsa21). While the resulting physiological and behavioral phenotypes vary in their penetrance and severity, all individuals with DS have variable but significant levels of cognitive disability. At the core of cognitive processes is the phenomenon of synaptic plasticity, a functional change in the strength at points of communication between neurons. A wide variety of evidence from studies on DS individuals and mouse models of DS indicates that synaptic plasticity is adversely affected in human trisomy 21 and mouse segmental trisomy 16, respectively, an outcome that almost certainly extensively contributes to the cognitive impairments associated with DS. In this review, we will highlight some of the neurophysiological changes that we believe reduce the ability of trisomic neurons to undergo neuroplasticity-related adaptations. We will focus primarily on hippocampal networks which appear to be particularly impacted in DS and where consequently the majority of cellular and neuronal network research has been performed using DS animal models, in particular the Ts65Dn mouse. Finally, we will postulate on how altered plasticity may contribute to the DS cognitive disability.
唐氏综合征（DS）是由人类 21 号染色体（Hsa21）上基因的三倍表达引起的。尽管由此产生的生理和行为表型在其外显率和严重程度上有所不同，但所有患有 DS 的个体都有不同程度但明显的认知障碍。在认知过程的核心是突触可塑性现象，即神经元之间通讯点的功能强度变化。来自对 DS 个体和 DS 小鼠模型的广泛研究证据表明，人类三体性 21 和小鼠节段性三体性 16 中的突触可塑性分别受到不利影响，这一结果几乎可以肯定会极大地导致与 DS 相关的认知障碍。在这篇综述中，我们将重点介绍一些我们认为会降低三体神经元进行与神经可塑性相关的适应性的神经生理学变化。我们将主要关注海马网络，该网络在 DS 中似乎受到特别影响，因此，大多数细胞和神经元网络研究都是使用 DS 动物模型进行的，特别是 Ts65Dn 小鼠。最后，我们将推测改变的可塑性如何导致 DS 的认知障碍。
