Department of Neuropathology (Nuffield Department of Clinical Neuroscience), Oxford University Hospitals, University of Oxford, United Kingdom; Department of Medicine (Neuroscience), Monash University, Australia; Royal Melbourne Hospital, Australia.
Dev Neurobiol. 2014 Jan;74(1):25-41. doi: 10.1002/dneu.22127. Epub 2013 Nov 4.
Autism is thought to be a neurodevelopmental disorder with symptoms developing during neonatal neurogenesis in the subventricular zone (SVZ). Autism associated genes alter SVZ proliferation and cytoarchitecture, yet the response of the human SVZ in autism is unknown. Epilepsy drives neurogenesis in rodents, but it is unclear how epilepsy interacts with autism in SVZ responses. The striatal and septal SVZ derive from separate lineages in rodents and generate different interneuron types. Yet it is unclear if autism unevenly regulates the striatal and septal SVZ. The human SVZ was immunohistochemically examined post-mortem from individuals with autism (n = 11) and controls (n = 11). Autism showed a lower cell density in the septal, but not striatal, SVZ hypocellular gap only in the absence of epilepsy. There was a decline in septal hypocellular gap cells with age in autism, but no correlation with age in controls. In contrast, PCNA+ cell numbers increased only in autism with epilepsy both in the hypocellular gap and in the ependymal layer on the septal but not striatal side. Ependymal cells also became GFAP immunoreactive in autism irrespective of epilepsy co-morbidity; however, this only occurred on the striatal side. In examining these questions we also discovered a subset of ependymal, astrocyte ribbon and RMS cells which express PCNA and Ki67, PLP, and α-tubulin. These results are the first example of a neuropsychiatric disease differentially affecting the septal and striatal SVZ. Altered cell density in the hypocellular gap and proliferation marker expression suggest individuals with autism may follow a different growth-trajectory.
自闭症被认为是一种神经发育障碍，其症状在脑室下区（SVZ）的新生儿神经发生期间发展。自闭症相关基因改变 SVZ 的增殖和细胞结构，但自闭症患者的 SVZ 反应尚不清楚。癫痫会促进啮齿动物的神经发生，但尚不清楚癫痫如何与 SVZ 反应中的自闭症相互作用。纹状体和隔区 SVZ 源自啮齿动物的不同谱系，并产生不同的中间神经元类型。然而，尚不清楚自闭症是否会不均匀地调节纹状体和隔区 SVZ。对自闭症患者（n = 11）和对照组（n = 11）的死后人类 SVZ 进行了免疫组织化学检查。自闭症患者的隔区 SVZ 细胞密度较低，但在没有癫痫的情况下，纹状体 SVZ 细胞密度较低的区域不存在细胞减少。自闭症患者的隔区细胞密度减少与年龄相关，但对照组无相关性。相比之下，仅在自闭症合并癫痫的患者中，PCNA+细胞数量在隔区的细胞密度较低的区域和室管膜层中增加，而不在纹状体侧增加。自闭症患者中无论是否存在癫痫合并症，室管膜细胞也会变得对 GFAP 免疫反应性；然而，这种情况仅发生在纹状体侧。在研究这些问题时，我们还发现了一小部分室管膜细胞、星形胶质细胞带和 RMS 细胞表达 PCNA 和 Ki67、PLP 和α-微管蛋白。这些结果是首例神经精神疾病对隔区和纹状体 SVZ 产生不同影响的例子。细胞密度减少和增殖标志物表达提示自闭症患者可能遵循不同的生长轨迹。
