Early-life exposure to PM2.5 leads to ASD-like phenotype in male offspring rats through activation of PI3K-AKT signaling pathway

• Published in: Ecotoxicology and environmental safety 2024-04, Vol.274, p.116222-116222, Article 116222
• Main Authors: Li, Kang, Liang, Xiaotian, Liu, Xiaohua, Geng, Yanpei, Yan, Jun, Tian, Lei, Liu, Huanliang, Lai, Wenqin, Shi, Yue, Xi, Zhuge, Lin, Bencheng
• Format: Article
• Language: English
• Subjects: Autism spectrum disorder; PI3K-AKT signaling pathway; PM2.5; PTEN; Sensitive period
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116222

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms. •Early postnatal PM2.5 exposure induced more pronounced ASD-like phenotype in male offspring rats than maternal exposure.•Early postnatal period may be a sensitive window for PM2.5 to trigger autism spectrum disorder development.•PM2.5 exposure caused neuroinflammation and reduced anti-inflammatory melatonin levels in offspring rat brains.•PI3K-AKT pathway activation may link developmental PM2.5 exposure and autism spectrum disorder pathogenesis.