Department of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
Acta Neuropathol Commun. 2014 Mar 10;2:28. doi: 10.1186/2051-5960-2-28.
Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon's horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.
已有几项形态计量学研究显示，自闭症患者的新皮质神经元体积小于正常。为了验证异常神经元生长是自闭症相关全脑炎的一个标志的假说，我们对 14 名自闭症患者（年龄 4 岁至 60 岁）和 14 名年龄匹配的对照组的 16 个脑区（包括各种皮质下结构、Ammon 角、古皮质、小脑和脑干）的神经元体积进行了估计。这项立体学研究表明，在 4 岁至 8 岁自闭症患者大脑的 16 个区域中有 14 个区域的神经元体体积明显小于对照组。任意分类显示，在 14.3%的明显改变的结构中存在非常严重的神经元体积缺陷，在 50%的结构中存在严重的缺陷，在 21.4%的结构中存在中度的缺陷，在 14.3%的结构中存在轻度的缺陷。这种模式表明，在自闭症表型涉及的相互作用神经元网络中，神经元生长不同步。自闭症和对照组大脑的比较研究表明，在 4 岁至 8 岁自闭症患者中，有明显体积缺陷的结构数量从 14 个减少到 36 岁至 60 岁的 4 个。自闭症成年人大脑中 75%的被检查结构的神经元体积与年龄匹配的对照组相似。这种模式表明，神经元生长缺陷发生在幼儿期，青春期和成年期神经元生长的上调延迟，从而减少了大多数被检查区域的神经元体体积缺陷。然而，神经元大小的显著校正但临床改善有限表明，延迟校正并不能恢复功能缺陷。
