Ma Yuan, Wang Kaidong, Jiao Yuxuan, Li Yujing, Hu Rong, Li Yang, Shi Ge, Huang Min
School of Public Health, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China.
School of Public Health, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No.1160, Shengli Street, Xingqing District, Yinchuan, Ningxia, China.
Toxicology. 2025 Aug;515:154128. doi: 10.1016/j.tox.2025.154128. Epub 2025 Apr 5.
Atrazine (ATR) is a widely utilized herbicide that has been demonstrated to exert a multitude of deleterious effects on the environment, particularly with regard to water and soil contamination. Moreover, its disruption of endocrine function and implications for antibiotic resistance underscore the urgent need to prioritize alternative solutions for both ecosystems and human health. Therefore, the objective of this study was to investigate a range of neurotoxic effects associated with atrazine-induced damage in the prefrontal lobe of mice. The results of this study indicate that treatment with ATR in C57BL/6 J mice resulted in cognitive-related behavioral deficits, including anxiety and depression, as well as motor impairments. In vivo analyses demonstrated that ATR exposure resulted in a reduction in neuronal synapse density at the microstructural level, while also compromising prefrontal morphological integrity, nociceptor count, and overall neuronal health within the brain. These findings collectively suggest that synaptic deficits are implicated in ATR-induced behavioral abnormalities observed in these mice. Furthermore, our findings revealed that ATR exposure resulted in elevated TDP-43 expression levels that were ectopically localized within the cytoplasm. This alteration led to impaired functionality of mRNP granules and contributed to the development of abnormal synaptic defects. Conversely, TDP-43 has the potential to localize ectopically to mitochondria, where it activates the mitochondrial unfolded protein response (UPRmt), which ultimately results in mitochondrial dysfunction. These findings collectively indicate a strong correlation between TDP-43 dysregulation and the progression of neurodegenerative diseases. Further investigation into the potential neurotoxicity of atrazine may foster heightened awareness, leading to more stringent regulatory measures, research into safer alternatives, and the adoption of sustainable practices, which are essential for safeguarding environmental integrity alongside human health.
阿特拉津（ATR）是一种广泛使用的除草剂，已被证明对环境有多种有害影响，特别是在水和土壤污染方面。此外，它对内分泌功能的破坏以及对抗生素耐药性的影响凸显了迫切需要优先为生态系统和人类健康寻求替代解决方案。因此，本研究的目的是调查与阿特拉津诱导的小鼠前额叶损伤相关的一系列神经毒性作用。本研究结果表明，在C57BL/6 J小鼠中用ATR处理导致与认知相关的行为缺陷，包括焦虑和抑郁，以及运动障碍。体内分析表明，ATR暴露导致微观结构水平上神经元突触密度降低，同时也损害了前额叶的形态完整性、伤害感受器数量和大脑内整体神经元健康。这些发现共同表明，突触缺陷与在这些小鼠中观察到的ATR诱导的行为异常有关。此外，我们的研究结果表明，ATR暴露导致TDP-43表达水平升高，其异位定位于细胞质中。这种改变导致mRNP颗粒功能受损，并导致异常突触缺陷的发展。相反，TDP-43有可能异位定位于线粒体，在那里它激活线粒体未折叠蛋白反应（UPRmt），最终导致线粒体功能障碍。这些发现共同表明TDP-43失调与神经退行性疾病的进展之间存在密切关联。对阿特拉津潜在神经毒性的进一步研究可能会提高人们的认识，从而导致更严格的监管措施、对更安全替代品的研究以及采用可持续做法，这些对于保护环境完整性和人类健康至关重要。
