Single prenatal exposure to valproic acid (VPA) in rodents is a widely used preclinical model of autism spectrum disorder (ASD). Continuous prenatal VPA exposure has been recently proposed as a new ASD model that closely captures the neuropathological features of ASD, including increases in cerebral cortex volume and the number of cortical upper layer neurons. We investigated the influence of prenatal VPA exposure on the behavior of adult offspring of pregnant dams that received intraperitoneal injections of VPA twice on one day during the genesis of cortical upper layer neurons. Mice exposed to VPA at E14 (E14-VPA) showed typical behavior abnormalities including reduced social interaction, hyperactivity, and poor maze learning due to attention deficit/impulsivity relative to healthy controls. Histological analysis revealed that E14-VPA mice had significantly increased neuronal density and impaired neural activity in the prefrontal cortex, but not the somatosensory area, which is likely linked to the observed abnormalities in social behavior. These results suggest that this VPA exposure method is a good model for gaining new insights into the underlying neuropathology of ASD.

中文翻译：

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成年小鼠中晚期皮质形成过程中接触丙戊酸会诱发学习和社交行为异常，并伴有注意力缺陷/多动。

啮齿动物的产前一次丙戊酸（VPA）暴露是自闭症谱系障碍（ASD）广泛使用的临床前模型。最近已提出连续产前VPA暴露作为一种新的ASD模型，可以密切捕获ASD的神经病理学特征，包括增加大脑皮层体积和皮层上层神经元的数量。我们调查了产前VPA暴露对在皮层上层神经元发生期间一天接受两次腹膜内注射VPA的怀孕大坝成年后代行为的影响。在E14暴露于VPA的小鼠（E14-VPA）表现出典型的行为异常，包括相对于健康对照组而言，注意力不足/冲动引起的社交互动减少，活动过度和迷宫学习不良。组织学分析显示，E14-VPA小鼠的额叶前额皮层神经元密度显着增加，神经活动受损，但体感区则没有，这可能与观察到的社交行为异常有关。这些结果表明，这种VPA暴露方法是获得有关ASD潜在神经病理学新见识的良好模型。