Neurodevelopmental disorders are congenital impairments, impeding the growth and development of the central nervous system. These disorders include autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder in Diagnostic and Statistical Manual of Mental Disorders-5. ASD is caused by a gene defect and chromosomal duplication. Despite numerous reports on ASD, the pathogenic mechanisms are not clear. The optimal methods to prevent ASD and to treat it are also not clear. Other studies have reported that endoplasmic reticulum (ER) stress contributes to the pathogenesis of neurodegenerative diseases. In this study, we have investigated ER stress condition and neuronal maturation in an ASD mice model employing male ICR mice.

An ASD mice model was established by injecting with valproic acid (VPA) into pregnant mice. The offspring born from VPA-treated mothers were subjected to the experiments as the ASD model mice. The cerebral cortex and hippocampus of ASD model mice were found to be under high ER stress. The mRNA levels of Hes1 and Pax6 were decreased in the cerebral cortex of the ASD model mice, but not in the hippocampus. In addition, the mRNA level in Math1 was increased in the cerebral cortex. ER stress inhibited dendrite and axon extension in primary culture derived from the cerebral cortex of E14.5 mice. Furthermore, dendrite outgrowth was suppressed in primary culture derived from the cerebral cortex of ASD model mice by the same method.

These results indicated the possibility that ER stress induces abnormal neuronal maturation in the embryonal cerebral cortex of ASD model mice employing male ICR mice. Therefore, ER stress may contribute to the pathogenesis of ASD.

神经发育障碍是先天性疾病，阻碍了中枢神经系统的生长和发育。这些疾病包括《精神障碍诊断和统计手册》 -5中的自闭症谱系障碍（ASD）和注意力不足/多动症。ASD是由基因缺陷和染色体重复引起的。尽管有关ASD的报道很多，但其致病机制尚不清楚。预防和治疗ASD的最佳方法也不清楚。其他研究已报道内质网（ER）应激有助于神经退行性疾病的发病机理。在这项研究中，我们已经调查了使用雄性ICR小鼠的ASD小鼠模型中的ER应激状态和神经元成熟。

通过将丙戊酸（VPA）注射到怀孕的小鼠中来建立ASD小鼠模型。将接受VPA处理的母亲的后代作为ASD模型小鼠进行实验。发现ASD模型小鼠的大脑皮层和海马处于高内质网应激状态。在ASD模型小鼠的大脑皮层中，Hes1和Pax6的mRNA水平降低，但在海马体中却没有。此外，Math1中的mRNA水平在大脑皮层中升高。ER应力抑制了E14.5小鼠大脑皮层的原代培养物中的树突和轴突延伸。此外，通过相同的方法，在源自ASD模型小鼠的大脑皮层的原代培养物中抑制了树突生长。

这些结果表明ER应激在采用雄性ICR小鼠的ASD模型小鼠的胚胎大脑皮层中诱导异常的神经元成熟的可能性。因此，内质网应激可能与自闭症的发病机制有关。