Laboratorio de Neurociencia Celular y Plasticidad, Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide, E-41013 Sevilla, Spain.
Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, E-41009, Sevilla, Spain; Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Servicio de Animalario, Hospital Universitario Virgen Macarena (HUVM), E-41009, Sevilla, Spain.
Neurobiol Dis. 2015 Oct;82:516-525. doi: 10.1016/j.nbd.2015.09.005. Epub 2015 Sep 24.
Down's syndrome (DS) is the most prevalent genetic intellectual disability. Memory deficits significantly contribute to the cognitive dysfunction in DS. Previously, we discovered that mTOR-dependent local translation, a pivotal process for some forms of synaptic plasticity, is deregulated in a DS mouse model. Here, we report that these mice exhibit deficits in both synaptic plasticity (i.e., BDNF-long term potentiation) and the persistence of spatial long-term memory. Interestingly, these deficits were fully reversible using rapamycin, a Food and Drug Administration-approved specific mTOR inhibitor; therefore, rapamycin may be a novel pharmacotherapy to improve cognition in DS.
唐氏综合征（DS）是最常见的遗传性智力障碍。记忆缺陷是导致 DS 认知功能障碍的主要原因。此前，我们发现 mTOR 依赖性局部翻译（一种对于某些形式的突触可塑性至关重要的过程）在 DS 小鼠模型中失调。在这里，我们报告这些小鼠在突触可塑性（即 BDNF 长时程增强）和空间长时记忆的持久性方面均存在缺陷。有趣的是，使用雷帕霉素（一种获得美国食品和药物管理局批准的特异性 mTOR 抑制剂）可完全逆转这些缺陷；因此，雷帕霉素可能是改善 DS 认知功能的一种新的药物治疗方法。
