Translational Research Group in Autism Spectrum Disorders-GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre,
Neuroglial Plasticity Group, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre,
Neuroimmunomodulation. 2018;25(5-6):285-299. doi: 10.1159/000492113. Epub 2018 Aug 29.
Autism spectrum disorder (ASD) is a highly prevalent developmental disorder characterized by deficits in communication and social interaction and in stereotyped or repetitive behaviors. Besides the classical behavioral dyad, several comorbidities are frequently present in patients with ASD, such as anxiety, epilepsy, sleep disturbances, and gastrointestinal tract dysfunction. Although the etiology of ASD remains unclear, there is supporting evidence for the involvement of both genetic and environmental factors. Valproic acid (VPA) is an anticonvulsant and mood stabilizer that, when used during the gestational period, increases the risk of ASD in the offspring. The animal model of autism induced by prenatal exposure to VPA demonstrates important structural and behavioral features that can be observed in individuals with autism; it is thus an excellent tool for testing new drug targets and developing novel behavioral and drug therapies. In addition, immunological alterations during pregnancy could affect the developing embryo because immune molecules can pass through the placental barrier. In fact, exposure to pathogens during the pregnancy is a known risk factor for ASD, and maternal immune activation can lead to autistic-like features in animals. Interestingly, neuroimmune alterations are common in both autistic individuals and in animal models of ASD. We summarize here the important alterations in inflammatory markers, such as cytokines and chemokines, in patients with ASD and in the VPA animal model.
自闭症谱系障碍（ASD）是一种高度流行的发育障碍，其特征是在沟通和社交互动以及刻板或重复行为方面存在缺陷。除了经典的行为对子，自闭症患者还经常存在多种共病，如焦虑、癫痫、睡眠障碍和胃肠道功能障碍。尽管 ASD 的病因仍不清楚，但有证据表明遗传和环境因素都参与其中。丙戊酸（VPA）是一种抗惊厥药和情绪稳定剂，在妊娠期使用时会增加后代患 ASD 的风险。VPA 产前暴露诱导的自闭症动物模型表现出重要的结构和行为特征，这些特征可以在自闭症患者中观察到；因此，它是测试新药物靶点和开发新的行为和药物治疗方法的极好工具。此外，怀孕期间的免疫改变可能会影响发育中的胚胎，因为免疫分子可以穿过胎盘屏障。事实上，怀孕期间接触病原体是 ASD 的已知风险因素，而母体免疫激活可导致动物出现类似自闭症的特征。有趣的是，神经免疫改变在自闭症患者和 ASD 动物模型中都很常见。我们在这里总结了 ASD 患者和 VPA 动物模型中炎症标志物（如细胞因子和趋化因子）的重要改变。
