Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China.
Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, PR China; Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang 110122, PR China.
Environ Int. 2024 Sep;191:108966. doi: 10.1016/j.envint.2024.108966. Epub 2024 Aug 17.
Triclosan (TCS) is an environmental pollutant. In recent years, there has been increasing level of concern regarding the potential toxicity of TCS in animals and humans, especially its effects on the nervous system. However, whether TCS induces ADHD-like behaviour and the mechanism by which it affects neural function are unclear. The impact of 60 days of continuous exposure to TCS on the behaviour of offspring rats was assessed in this research. According to the results of this study, TCS exposure led to ADHD-like behaviour in offspring rats and activated microglia in the prefrontal cortex (PFC), inducing inflammatory factor release. In vitro studies showed that TCS increased the levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, in HMC3 cells. More importantly, we found that TCS regulated the STAT3 pathway by upregulating PKM2 via hnRNPA1. In summary, this study suggested that TCS can induce ADHD-like behaviour in offspring rats and continuously activate HMC3 microglia through the hnRNPA1-PKM2-STAT3 feedback loop, promoting inflammatory cytokine secretion.
三氯生（TCS）是一种环境污染物。近年来，人们越来越关注 TCS 对动物和人类的潜在毒性，尤其是其对神经系统的影响。然而，TCS 是否会引起 ADHD 样行为以及它影响神经功能的机制尚不清楚。本研究评估了连续 60 天暴露于 TCS 对后代大鼠行为的影响。研究结果表明，TCS 暴露导致后代大鼠出现 ADHD 样行为，并激活前额叶皮层（PFC）中的小胶质细胞，诱导炎症因子释放。体外研究表明，TCS 增加了 HMC3 细胞中炎症细胞因子（包括白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α）的水平。更重要的是，我们发现 TCS 通过 hnRNPA1 上调 PKM2 来调节 STAT3 通路。总之，这项研究表明，TCS 可诱导后代大鼠出现 ADHD 样行为，并通过 hnRNPA1-PKM2-STAT3 反馈回路持续激活 HMC3 小胶质细胞，促进炎症细胞因子的分泌。
