Wegiel Jarek, Flory Michael, Kaczmarski Wojciech, Brown W Ted, Chadman Kathryn, Wisniewski Thomas, Nowicki Krzysztof, Kuchna Izabela, Ma Shuang Yong, Wegiel Jerzy
Departments of Developmental Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
Research Design and Analysis Services, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
J Neuropathol Exp Neurol. 2017 Mar 1;76(3):225-237. doi: 10.1093/jnen/nlx003.
To test the hypothesis that developmental anomalies of the corpus callosum (CC), contribute to the pathogenesis of autism, we characterized the type, topography, and severity of CC pathology corresponding to reduced CC areas that are detected by magnetic resonance imaging in the brains of 11 individuals with autism and 11 controls. In the brains of 3 autistic subjects, partial CC agenesis resulted in complete or partial lack of interhemispheric axonal connections in CC segments III-V. In these cases, a combination of focal agenesis and uniform axonal deficit caused reduction of CC areas by 37%, of axon numbers by 62%, and of the numerical density of axons by 39%. In the CC of 8 autistic subjects without agenesis, there was an 18% deficit of the midsagittal CC area, 48.4% deficit of axon numbers, and 37% reduction of the numerical density of axons. The significantly thinner CC, reduced CC area, and uniform axonal deficit in all autistic subjects were classified as CC hypoplasia. Thus, the byproduct of partial CC agenesis and hypoplasia is reduction of axonal connections between cortical areas known to be involved in behavioral alterations observed in people with autism.
为了验证胼胝体发育异常(CC)导致自闭症发病机制的假说,我们对11名自闭症患者和11名对照者大脑中磁共振成像检测到的胼胝体面积减小所对应的CC病理类型、位置及严重程度进行了特征分析。在3名自闭症受试者的大脑中,部分胼胝体发育不全导致CC的III-V节段完全或部分缺乏半球间轴突连接。在这些病例中,局灶性发育不全和均匀性轴突缺失共同导致CC面积减少37%,轴突数量减少62%,轴突数量密度降低39%。在8名无发育不全的自闭症受试者的胼胝体中,矢状面中部胼胝体面积缺失18%,轴突数量缺失48.4%,轴突数量密度降低37%。所有自闭症受试者中明显变薄的胼胝体、减小的胼胝体面积和均匀性轴突缺失被归类为胼胝体发育不全。因此,部分胼胝体发育不全和发育不全的副产品是已知与自闭症患者行为改变有关的皮质区域之间轴突连接的减少。