美国贝勒医学院Huda Y. Zoghbi研究小组取得一项新突破。他们发现在Rett综合征症状发生前进行训练有助于减轻患病小鼠的功能缺陷。这一研究成果在线发表在2021年3月24日的《自然》上。
目前尚无有效治疗Rett综合征的方法，研究人员认为利用正常发育时期来增强运动和记忆能力可能会带来一些好处。
研究人员使用Rett综合征小鼠模型发现，在Rett综合征症状产生前开始的强化训练可以显著改善特定运动和记忆任务的性能，并可明显延迟症状发作。在症状发作后开始训练并未观察到这些益处。神经元活动和化学发生标志物表明，与未经训练的动物相比，在训练过程中反复激活的任务特定神经元会产生更多的树突状树突，并具有更好的神经生理反应，从而增强了它们的功能并延迟症状发作。
这些结果为Rett综合征的新生儿基因筛查提供了理论依据，因为症状前干预可能会减轻症状或延缓其发作。对于其他儿童神经系统疾病，应研究类似的策略。
据了解，X染色体连锁基因MECP2突变会引起Rett综合征，这是一种进行性神经系统疾病，患有该病的儿童会在生命开始的前一两年内正常发育，随后则产生严重的运动和认知能力下降。
附：英文原文
Title: Presymptomatic training mitigates functional deficits in a mouse model of Rett syndrome
Author: Nathan P. Achilly, Wei Wang, Huda Y. Zoghbi
Issue&Volume: 2021-03-24
Abstract: Mutations in the X-linked gene MECP2 cause Rett syndrome, a progressive neurological disorder in which children develop normally for the first one or two years of life before experiencing profound motor and cognitive decline1,2,3. At present there are no effective treatments for Rett syndrome, but we hypothesized that using the period of normal development to strengthen motor and memory skills might confer some benefit. Here we find, using a mouse model of Rett syndrome, that intensive training beginning in the presymptomatic period dramatically improves the performance of specific motor and memory tasks, and significantly delays the onset of symptoms. These benefits are not observed when the training begins after symptom onset. Markers of neuronal activity and chemogenetic manipulation reveal that task-specific neurons that are repeatedly activated during training develop more dendritic arbors and have better neurophysiological responses than those in untrained animals, thereby enhancing their functionality and delaying symptom onset. These results provide a rationale for genetic screening of newborns for Rett syndrome, as presymptomatic intervention might mitigate symptoms or delay their onset. Similar strategies should be studied for other childhood neurological disorders.
DOI: 10.1038/s41586-021-03369-7
Source: https://www.nature.com/articles/s41586-021-03369-7
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
