Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders characterized by movement and social deficits with rapidly increasing incidence worldwide. Propionic acid (PPA) is a histone deacetylase inhibitor that regulates neuronal plasticity in the brain. Evaluation of the behavioral and cellular consequences of PPA exposure during a critical neurodevelopmental window is required. Therefore, in the present study we aimed to evaluate the effects of prenatal PPA exposure on locomotor behavior and astrocyte number, as well as on levels of nitric oxide (NO), synaptophysin (SYP; a marker of synaptic plasticity), and metallothionein 3 (MT-III; a marker of reactive oxygen species and zinc metabolism), in the prefrontal cortex (PFC) of male rats. All parameters were evaluated at three critical ages of development: postnatal days (PD) 21 (weaning age), PD35 (pre-pubertal age) and PD70 (post-pubertal age). Prenatal PPA exposure induced hypolocomotion and decreased rearing events at weaning age. Moreover, astrogliosis in the PFC was observed in PPA-treated rats at pre- and post-pubertal age. SYP levels were dramatically decreased in PPA-treated rats with simultaneous astrogliosis, suggesting reduced synaptic plasticity. MT-III expression was deregulated in PPA-treated rats. Finally, the expression of NO in the PFC remained unaltered in PPA-treated rats. These results mimic behavioral, neuronal and astrocytic characteristics observed in ASD patients.

自闭症谱系障碍 (ASD) 是一系列以运动和社交障碍为特征的神经发育障碍，在全球范围内发病率迅速增加。丙酸 (PPA) 是一种组蛋白去乙酰化酶抑制剂，可调节大脑中的神经元可塑性。需要在关键的神经发育窗口期间评估 PPA 暴露的行为和细胞后果。因此，在本研究中，我们旨在评估产前 PPA 暴露对运动行为和星形胶质细胞数量以及一氧化氮 (NO)、突触素 (SYP；突触可塑性标志物) 和金属硫蛋白 3 水平的影响。 MT-III；活性氧和锌代谢的标志物），位于雄性大鼠的前额叶皮层 (PFC)。所有参数都在三个关键的发育年龄进行了评估：产后天数 (PD) 21（断奶年龄）、PD35（青春期前年龄）和 PD70（青春期后年龄）。产前暴露于 PPA 会导致运动不足并减少断奶时的饲养事件。此外，在 PPA 治疗的大鼠青春期前和青春期后观察到 PFC 中的星形胶质细胞增生。PPA 治疗的大鼠同时发生星形胶质细胞增生，SYP 水平显着降低，表明突触可塑性降低。MT-III 表达在 PPA 处理的大鼠中失调。最后，PFC 中 NO 的表达在 PPA 处理的大鼠中保持不变。这些结果模拟了在 ASD 患者中观察到的行为、神经元和星形胶质细胞特征。在 PPA 治疗的大鼠青春期前和青春期后观察到 PFC 中的星形胶质细胞增生。PPA 治疗的大鼠同时发生星形胶质细胞增生，SYP 水平显着降低，表明突触可塑性降低。MT-III 表达在 PPA 处理的大鼠中失调。最后，PFC 中 NO 的表达在 PPA 处理的大鼠中保持不变。这些结果模拟了在 ASD 患者中观察到的行为、神经元和星形胶质细胞特征。在 PPA 治疗的大鼠青春期前和青春期后观察到 PFC 中的星形胶质细胞增生。PPA 治疗的大鼠同时发生星形胶质细胞增生，SYP 水平显着降低，表明突触可塑性降低。MT-III 表达在 PPA 处理的大鼠中失调。最后，PFC 中 NO 的表达在 PPA 处理的大鼠中保持不变。这些结果模拟了在 ASD 患者中观察到的行为、神经元和星形胶质细胞特征。