Changes in prefrontal axons may disrupt the network in autism.
Changes in prefrontal axons may disrupt the network in autism.
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DOI：
10.1523/jneurosci.2257-10.2010
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发表时间：
2010-11-03
期刊：
影响因子：
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通讯作者：
Barbas H
中科院分区：
文献类型：
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作者：
Zikopoulos B;Barbas H
自闭症患者的神经交流被未知的机制中断。在这里，我们研究了自闭症患者的轴突是否发生了变化，轴突是神经通讯的管道。我们研究了单个轴突及其超微结构的白色物质的死后人脑组织下的前扣带皮层（ACC），眶额（OFC），和外侧（LPFC）前额叶皮质，这是与注意力，社会交往，情绪和一直牵连在自闭症的病理。ACC（32区）以下的特定区域变化包括长距离通信的最大轴突减少。此外，ACC下方存在生长相关蛋白43的过度表达，伴随着连接相邻区域的过多数量的细轴突。在OFC（11区）轴突髓鞘厚度减少。LPFC（46区）下方的轴突功能似乎不受影响，但ACC和OFC下方改变的白色物质组成改变了所有前额叶区域之间的关系，并可能间接影响LPFC功能。这些发现提供了一种机制，用于断开长距离通路，相邻区域之间的过度连接，以及情感通路的低效，并可能有助于解释为什么自闭症患者不能充分转移注意力，从事重复行为，并避免社交互动。这些变化低于特定的前额叶区域似乎是通过一系列影响轴突生长和指导的发育事件联系在一起的，并建议针对相关的信号通路进行自闭症的治疗干预。
Neural communication is disrupted in autism by unknown mechanisms. Here we examined whether in autism there are changes in axons, which are the conduit for neural communication. We investigated single axons and their ultrastructure in the white matter of post-mortem human brain tissue below the anterior cingulate cortex (ACC), orbitofrontal (OFC), and lateral (LPFC) prefrontal cortices, which are associated with attention, social interactions, and emotions and have been consistently implicated in the pathology of autism. Area-specific changes below ACC (area 32) included a decrease in the largest axons that communicate over long distances. In addition, below ACC there was over-expression of the Growth Associated Protein 43 accompanied by excessive number of thin axons that link neighboring areas. In OFC (area 11) axons had decreased myelin thickness. Axon features below LPFC (area 46) appeared to be unaffected, but the altered white matter composition below ACC and OFC changed the relationship between all prefrontal areas examined, and could indirectly affect LPFC function. These findings provide a mechanism for disconnection of long distance pathways, excessive connections between neighboring areas, and inefficiency in pathways for emotions, and may help explain why individuals with autism do not adequately shift attention, engage in repetitive behavior, and avoid social interactions. These changes below specific prefrontal areas appear to be linked through a cascade of developmental events affecting axon growth and guidance, and suggest targeting the associated signaling pathways for therapeutic interventions in autism.