Trisomy 21, also known as Down syndrome (DS), is the most frequent genetic cause of intellectual impairment. In mouse models of DS, deficits in hippocampal synaptic plasticity have been observed, in conjunction with alterations to local dendritic translation that are likely to influence plasticity, learning and memory. Here we show that expression of a local translational regulator, the Cytoplasmic Polyadenylation Element Binding Protein 1 (CPEB1), is enhanced in hippocampal neurons from the Ts1Cje DS mouse model. Interestingly, this protein, which is also involved in dendritic mRNA transport, is overexpressed in dendrites of neurons derived from DS human induced pluripotent stem cells (hIPSCs). Moreover, there is an increase in the mRNA levels of α-Calmodulin Kinase II (α-CaMKII) and Microtubule-associated protein 1B (MAP1B), two dendritic mRNAs, in Ts1Cje synaptoneurosomes. Taking into account the fundamental role of CPEB1 protein and its target mRNAs in synaptic plasticity, these data could be relevant to the intellectual impairment in the context of DS.

21三体综合征，也称为唐氏综合症（DS），是智力障碍最常见的遗传原因。在DS的小鼠模型中，已经观察到海马突触可塑性的缺陷，以及可能影响可塑性，学习和记忆的局部树突状翻译的改变。在这里，我们显示从Ts1Cje DS小鼠模型在海马神经元中增强了局部翻译调节因子胞质多腺苷酸化元素结合蛋白1（CPEB1）的表达。有趣的是，这种蛋白质也参与树突状mRNA的运输，在DS人类诱导的多能干细胞（hIPSCs）衍生的神经元树突中过表达。此外，存在的增加的mRNA水平α -钙调蛋白激酶II（α -的CaMKII）和微管-相关蛋白1B（MAP1B），两个树枝状的mRNA，在Ts1Cje synaptoneurosomes。考虑到CPEB1蛋白及其靶mRNA在突触可塑性中的基本作用，这些数据可能与DS方面的智力障碍有关。