为什么大脑发育偏离正常的自闭症谱系障碍

雷特综合征模型表明，从环境中的处理线索的赤字

波士顿—雷特综合征在神经发育障碍，自闭症谱系，标志着相对正常的发展在起步阶段，其次是损失的认知，社会和语言技能，从12到18个月的年龄。它越来越被视为一种突触的紊乱，在一起形成大脑回路的神经元之间的连接。尚不清楚的是，为什么孩子们通常开始发育正常，只是逐渐变得异常。新研究波士顿儿童医院，发表于4月14日发行的神经元，有助于解开发生了什么。

研究人员，领导清妃陈，医学博士，哲学博士，儿童F。M。 Kirby神经生物学中心, studied synapse development in mice with a mutation in the Mecp2 gene, the same gene linked to human 雷特综合征。 They found strong evidence that the loss of functioning Mecp2 prevents synapses 和 circuits from maturing 和 refining in response to cues from the environment - just at the time when babies' brains should be maximally receptive to these cues。

Chen believes her findings may have implications not just for 雷特综合征, but for other 自闭症谱系 disorders。 "Many ASDs manifest between 1 和 2 years of age, a period when kids are interacting more with the outside world," says Chen。 "The brain of an autistic child looks normal, but there's a subtle difference in connections that has to do with how they process experiences。 If you could diagnose early enough, there might be a way to alter the course of the disease by modifying experience, such as through intense one-to-one therapy。"

陈和他的同事的研究主要集中在大脑的视觉系统的突触电路，是比较容易学习，称为retinogeniculate突触。它连接从眼睛接收输入到外侧膝状体细胞，在大脑的丘脑的重要中继站。从外部世界的视觉输入，在特定的“关键时期”是至关重要的，其正常发展。

该研究小组通过刺激视神经束和测量丘脑的电反应，测试了电路的功能，看看神经元是如何连接的，以及连接的连接有多强。MeCP2的突变小鼠，这些录音表明，通常先形成视觉电路，和生活在第二周，弱连接修剪和其他加强，正如他们应该。

但人生的后21天的小鼠后，打开他们的眼睛，当视觉电路应进一步削减和基于视觉经验强化它变得异常。输入和连接的数量实际上增加，而强度的突触减少。

这种模式类似于正常小鼠在21天的黑暗中被发现，剥夺了他们的视觉刺激。在一起，结果表明MeCP2是我们提炼的突触电路基于感官经验的能力至关重要，说陈。没有MECP2，电路不能纳入这一经验。

“在这最后阶段的发展，你需要感觉输入锁定和稳定的连接，”陈解释说。但是，该电路没有得到正确的信号，以稳定，并继续寻找正确的连接。”

In patients with 雷特综合征, the reduction in Mecp2 levels is especially striking in the thalamus, which processes 和 relays sensory information to the cortex, where thought, memory 和 language reside。 "It's very telling that we see these synaptic abnormalities in the thalamus, which is like a switchboard operator for the brain," says Chen。 "A small disruption in the thalamus can radiate to large areas of the cortex。"

This model of 雷特综合征 is consistent with mouse models of other autism-related disorders like易碎的和Angelman综合征研究者们说，在经历依赖性成熟的电路时，也表现出异常。

“有可能是一个问题，如何采取的信息，”陈说。被认为是不同的，所以反应是不同的。”

Chen 和 colleagues are now investigating whether reactivating Mecp2 at different times could improve organization of the visual circuitry。

Joao Noutel was the study's first author。 The study was supported by the National Institutes of Health 和 the Fundacao para a Ciencia e Tecnologia, Portugal。

接触：
科琳康纳利
617-919-3110
colleen。connolly@childrens。harvard。edu

波士顿儿童医院 is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children 和 adults since 1869。 More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine 和 13 members of the Howard Hughes Medical Institute comprise Children's research community。 Founded as a 20-bed hospital for children, 波士顿儿童医院 today is a 392-bed comprehensive center for pediatric 和 adolescent health care grounded in the values of excellence in patient care 和 sensitivity to the complex needs 和 diversity of children 和 families。 Children's also is the primary pediatric teaching affiliate of Harvard Medical School。 For more information about research 和 clinical innovation at Boston Children's visit:向量博客。

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