The broad impairments in cognitive and neurologic functioning found in Autism Spectrum Disorder (ASD) patients are thought to originate during early prenatal developmental stages. Indeed, postmortem and imaging studies in ASD patients detected white-matter abnormalities, as well as prefrontal and temporal cortex deficits, evident from early childhood. Here, we used Maternal Immune Activation (MIA), a mouse model for ASD, in which the offsprings exhibit Autistic-like behaviors as well as cortical abnormalities. However, the dynamics that influence the number and the identity of newly born cortical neurons following maternal inflammation remains unknown. Our study shows early changes in the duration of the S-phase of PAX6⁺ progenitors, leading to an increased proportion of neurogenic divisions and a reciprocal decrease in the proliferative divisions. In two different time points of maternal inflammation, MIA resulted in an overproduction of CTIP2⁺ cortical neurons, which remained overrepresented at the end of gestation and in postnatal mice. Interestingly, MIA-resistant IL6-KO mice did not exhibit these changes. Lastly, we propose that elevated levels of the transcription factor PAX6 following MIA supports the overproduction of CTIP2⁺ neurons. Taken together, our data reveals a possible link between maternal immune activation and the excess of cortical neurons found in the cortex of ASD patients.

在自闭症谱系障碍 (ASD) 患者中发现的广泛的认知和神经功能障碍被认为起源于产前早期发育阶段。事实上，自闭症谱系障碍患者的尸检和影像学研究检测到白质异常，以及前额叶和颞叶皮质缺陷，从儿童早期就很明显。在这里，我们使用了母体免疫激活 (MIA)，这是一种用于 ASD 的小鼠模型，其中后代表现出类似自闭症的行为以及皮质异常。然而，影响母体炎症后新生皮层神经元数量和特性的动力学仍然未知。^{我们的研究显示 PAX6 +} S 期持续时间的早期变化祖细胞，导致神经源性分裂的比例增加和增殖分裂的相互减少。在母体炎症的两个不同时间点，MIA 导致 CTIP2 ⁺皮质神经元的过量产生，在妊娠结束时和产后小鼠中仍然过多。有趣的是，MIA 抗性 IL6-KO 小鼠没有表现出这些变化。最后，我们提出 MIA 后转录因子 PAX6 水平的升高支持 CTIP2 ⁺神经元的过度生产。总之，我们的数据揭示了母体免疫激活与 ASD 患者皮质中发现的过多皮质神经元之间可能存在联系。