Data from: Early postnatal exposure to airborne fine particulate matter induces autism-like phenotypes in male rats

Epidemiological studies have revealed that ambient fine particulate matter (PM2.5) exposure is closely associated with autism spectrum disorder (ASD). However, there is a relative paucity of laboratory data to support this epidemic finding. In order to assess the relationship between PM2.5 exposure and ASD, neonatal male Sprague-Dawley (SD) rats were chosen and exposed to PM2.5 (2 or 20 mg/kg body weight, once a day) by intranasal instillation from postnatal day (PND) 8 to 22. It was found that when exposed to PM2.5 in the early neonatal period for two weeks, both groups of the exposure rats manifested typical behavioral features of autism, including communication deficits, poor social interaction and novelty avoidance. And, we further found, among five ASD candidate genes we chose, both the mRNA level and protein expression of SH3 and multiple ankyrin repeat domains 3 (Shank3) decreased significantly in the rat hippocampus after high dose of PM2.5 exposure. Moreover, results showed that PM2.5-exposure significantly increased the levels of pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α in the hippocampus and prefrontal cortex. The expression of Glial fibrillary acidic protein (GFAP) and ionized binding calcium adapter molecule (IBA1), markers of astrocytes and microglial cell activation, respectively, also increased in the exposed animals. Our work provides new data on the link between postnatal exposure to ambient PM2.5 and the onset of ASD-like symptoms in human beings, and the increased inflammatory response and abnormalities in Shank3 expression in the brain may contribute to the mechanisms of PM2.5 exposure induced ASD.

流行病学研究表明，环境细颗粒物（PM2.5）暴露与孤独症谱系障碍（ASD）密切相关，但目前支持这一流行病学发现的实验室数据相对匮乏。为评估PM2.5暴露与ASD之间的关联，本研究选取新生雄性斯普拉格-道利（SD）大鼠，于出生后第8天至第22天通过鼻腔滴注法暴露于PM2.5（剂量分别为2或20 mg/kg体重，每日一次）。研究发现，在新生早期暴露于PM2.5两周后，两个暴露组大鼠均表现出典型的孤独症样行为特征，包括沟通障碍、社交互动缺陷及新奇物回避行为。进一步检测所选的5个ASD候选基因发现，高剂量PM2.5暴露组大鼠海马体中SH3结构域和多个锚蛋白重复序列3（Shank3）的mRNA表达水平与蛋白表达量均显著降低。此外，实验结果显示，PM2.5暴露可显著升高大鼠海马体与前额叶皮层中促炎细胞因子白细胞介素1β（IL-1β）、白细胞介素6（IL-6）及肿瘤坏死因子α（TNF-α）的水平；星形胶质细胞活化标志物胶质纤维酸性蛋白（GFAP）与小胶质细胞活化标志物离子钙接头蛋白分子1（IBA1）的表达在暴露组动物体内也均有所上调。本研究为出生后暴露于环境PM2.5与人类孤独症样症状发作之间的关联提供了新的实验数据，而脑部炎症反应增强及Shank3表达异常可能是PM2.5暴露诱导ASD发生的潜在机制。