Division of Experimental Neuroscience, Department of Clinical Neuroscience, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Neurotoxicol Teratol. 2013 Mar-Apr;36:57-66. doi: 10.1016/j.ntt.2012.08.005. Epub 2012 Aug 28.
Autism spectrum disorder (ASD) is a behaviourally defined brain disorder affecting approximately 1 in 88 children. Many pathological studies have shown that ASD is frequently associated with grey and white matter changes that can be described by their deviations from the normal trajectory of cortical maturation. For example, during the early (i.e. <2 years) postnatal period there is marked and selective tissue overgrowth in the higher-order temporal and frontal networks involved in emotional, social, and communication functions. In this focused review we first summarize some basic principles of neocortical neural organization and how they are disrupted in ASD. We will then highlight some of the potential mechanisms by which the normal developmental trajectory and organization of neocortical networks can be altered based on animal studies of valproic acid, a teratogen widely used in animal models of ASD. We argue that the trajectory of postnatal cerebral neocortex development may be influenced by several cellular and molecular mechanisms that may all converge to produce a neuropathology characterized by premature or accelerated neuronal growth.
自闭症谱系障碍（ASD）是一种行为定义的大脑障碍，影响大约每 88 名儿童中有 1 名。许多病理学研究表明，ASD 经常与灰质和白质变化相关，这些变化可以通过其偏离皮质成熟的正常轨迹来描述。例如，在早期（即<2 岁）产后期间，涉及情感、社交和沟通功能的高级颞叶和额叶网络中的组织存在明显且选择性的过度生长。在本次重点综述中，我们首先总结了新皮层神经组织的一些基本原则，以及它们在 ASD 中是如何被破坏的。然后，我们将根据丙戊酸（一种广泛用于 ASD 动物模型的致畸剂）的动物研究，强调一些正常发育轨迹和新皮层网络组织可能被改变的潜在机制。我们认为，产后大脑新皮层发育的轨迹可能受到几种细胞和分子机制的影响，这些机制可能都汇聚在一起，产生一种以过早或加速神经元生长为特征的神经病理学。
