Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.

中文翻译：

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用雷帕霉素进行产前治疗可恢复唐氏综合征小鼠模型中增强的海马 mGluR-LTD 和蘑菇脊柱大小

唐氏综合症 (DS) 是智力障碍最常见的遗传原因，包括海马依赖性记忆缺陷。我们之前曾报道过 Ts1Cje 小鼠（一种 DS 实验模型）的海马 mTOR（雷帕霉素的哺乳动物靶标）过度激活，以及相关的可塑性和记忆缺陷。在这里，我们对这些小鼠的海马突触神经小体 (SN) 的蛋白质组进行了表征，并发现了突触可塑性途径的预测改变，包括长期抑制 (LTD)。因此，mGluR-LTD（代谢型谷氨酸受体-LTD）在 Ts1Cje 小鼠的海马中增强，这与海马锥体神经元中特定类别蘑菇刺的比例增加有关。值得注意的是，