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Understanding the molecular pathway of triclosan-induced ADHD-like behaviour: Involvement of the hnRNPA1-PKM2-STAT3 feedback loop
Environment International ( IF 10.3 ) Pub Date : 2024-08-17 , DOI: 10.1016/j.envint.2024.108966
Chang Shu 1 , He Cui 1 , Yuxuan Peng 1 , Ziyun Wei 1 , Xiao Ni 1 , Linlin Zheng 1 , Jianing Shang 1 , Fu Liu 1 , Jieyu Liu 2
Affiliation  

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.

中文翻译:


了解三氯生诱导的 ADHD 样行为的分子途径:hnRNPA1-PKM2-STAT3 反馈环路的参与



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,特别是其对神经系统的影响。然而,TCS是否会诱发ADHD样行为及其影响神经功能的机制尚不清楚。本研究评估了连续暴露于 TCS 60 天对子代大鼠行为的影响。根据这项研究的结果,TCS 暴露会导致子代大鼠出现 ADHD 样行为,并激活前额皮质 (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的水平,包括白细胞介素 (IL)-1β、IL-6 和肿瘤坏死因子 (TNF)-α。更重要的是,我们发现TCS通过hnRNPA1上调PKM2来调节STAT3通路。综上所述,本研究表明TCS可以诱导子代大鼠出现ADHD样行为,并通过hnRNPA1-PKM2-STAT3反馈环路持续激活HMC3小胶质细胞,促进炎症细胞因子的分泌。
更新日期:2024-08-17
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