孤独症谱系障碍ASD的症状包括社交技能减弱、交流能力受损和重复性行为等。日前,来自美国纽约大学神经科学研究中心的研究人员在ASD小鼠实验中,成功使大脑中过量的蛋白合成恢复正常,治愈了小鼠的上述孤独症行为。

-2013年1月17日《自然》

中文翻译


【题目】过度翻译会引起自闭症相关的突触和行为异常

【译文】自闭症谱系障碍(ASD)是一种早发的异质性可遗传神经障碍,其症状包括社交能力缺陷、受损的交流能力以及刻板样重复行为。对于ASD潜在的常见分子机制的一个假说就是改变的翻译调控导致了过度蛋白合成。在自闭症患者中已经发现染色体4q(包含EIF4E位点)上的遗传突变。重要的是,一种稀有的单核苷酸多态性已在自闭症中被鉴定出来,它与EIF4E基因内启动子活性增加相关。本研究表明遗传性增加小鼠中真核生物翻译起始因子4E(eIF4E)的水平会导致过度的cap依赖的翻译和自闭症的异常行为,包括重复和持续性行为以及社交能力缺陷。此外,这些自闭症样行为伴随着中间额前皮质、纹状体和海马体中的突触病理。eIF4E转基因小鼠表现的自闭症样行为可通过脑室内输入帽依赖翻译抑制因子4EGI-1而得到纠正。我们的发现证实了过度帽依赖翻译、突触失调和自闭症相关异常行为之间的因果关系。

英文原稿


[Title]: Exaggerated translation causes synaptic and behavioural aberrations associated with autism

[Authors]:Emanuela Santini,1 Thu N. Huynh,1 Andrew F. MacAskill,1 Adam G. Carter,1 Philippe Pierre,2, 3, 4 Davide Ruggero,5, 6 Hanoch Kaphzan1, 7, 6 & Eric Klann1

[Abstract]Autism spectrum disorders (ASDs) are an early onset, heterogeneous group of heritable neuropsychiatric disorders with symptoms that include deficits in social interaction skills, impaired communication abilities, and ritualistic-like repetitive behaviours. One of the hypotheses for a common molecular mechanism underlying ASDs is altered translational control resulting in exaggerated protein synthesis. Genetic variants in chromosome 4q, which contains the EIF4E locus, have been described in patients with autism. Importantly, a rare single nucleotide polymorphism has been identified in autism that is associated with increased promoter activity in the EIF4E gene. Here we show that genetically increasing the levels of eukaryotic translation initiation factor 4E (eIF4E) in mice results in exaggerated cap-dependent translation and aberrant behaviours reminiscent of autism, including repetitive and perseverative behaviours and social interaction deficits. Moreover, these autistic-like behaviours are accompanied by synaptic pathophysiology in the medial prefrontal cortex, striatum and hippocampus. The autistic-like behaviours displayed by the eIF4E-transgenic mice are corrected by intracerebroventricular infusions of the cap-dependent translation inhibitor 4EGI-1. Our findings demonstrate a causal relationship between exaggerated cap-dependent translation, synaptic dysfunction and aberrant behaviours associated with autism.

原文地址

http://www.nature.com/nature/journal/v493/n7432/full/nature11782.html

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