Understanding the molecular pathway of triclosan-induced ADHD-like behaviour: Involvement of the hnRNPA1-PKM2-STAT3 feedback loop

作者：Chang Shu, He Cui, Yuxuan Peng, Ziyun Wei, Xiao Ni, Linlin Zheng, Jianing Shang, Fu Liu, Jieyu Liu · 发表于：Environment International · 年份：2024 · DOI：10.1016/j.envint.2024.108966 · 被引用次数：5 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol、Neuroscience and Neuropharmacology Research

• TCS exposure induced ADHD-like behaviour in offspring rats. • TCS exposure activated microglia and induced them to release inflammatory cytokines. • TCS mediated the secretion of inflammatory cytokines via the hnRNPA1-PKM2-STAT3 feedback loop. 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.