Wu Jiaying, You Xinyue, Cao Yiyi, Xi Jing, Chen Xiang, Zhang Xinyu, Luan Yang
School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336, China.
School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China.
Environ Pollut. 2025 Jul 10;383:126814. doi: 10.1016/j.envpol.2025.126814.
Neonicotinoids (NEOs) have been widely used as effective pesticides for decades, yet their adverse effects on non-target organisms remain a growing concern. Although the neurotoxicity of certain NEOs has been established, the potential neurotoxicity of the remaining large fraction of NEOs, as well as their underlying mechanisms, are yet to be clarified. In the present study, we employed a high-throughput toxicity screening platform to evaluate the neurotoxic potential of eight commonly used neonicotinoid insecticides in Caenorhabditis elegans. Our results revealed that acetamiprid (ACE), dinotefuran (DIN), clothianidin (CLO) and thiacloprid (THI) significantly impaired locomotion behavior in worms. Upon examining the potential mechanism of action, we found that ACE, CLO and THI could induce serotonergic neuronal damage, while cholinergic, dopaminergic and GABAergic neurons remained unaffected. Additionally, these three NEOs reduced bend frequency by predominantly enhancing oxidative stress, which was partially mitigated by the antioxidant N-acetyl-L-cysteine. In the neurotransmitter system, ACE mainly upregulated the mRNA expression of synthesis- and transport-related genes of neurotransmitters, while THI increased transport-related gene expression and decreased GABAergic receptor gene expression. In contrast, DIN elevated total acetylcholine levels without significantly altering gene expression, suggesting a distinct mechanism. In summary, our findings highlight that ACE, CLO and THI exert neurotoxicity through oxidative stress and serotonergic neuronal damage, while DIN primarily disrupts the neurotransmitter system. Our study provides insights into the high-throughput screening of NEO-induced neurotoxicity, offering a critical foundation for future in-depth studies to fully elucidate the toxic mechanisms of NEOs and to assess their environmental and health risks.
几十年来，新烟碱类农药（NEOs）作为有效的杀虫剂被广泛使用，但其对非靶标生物的不利影响仍日益受到关注。尽管某些新烟碱类农药的神经毒性已得到证实，但其余大部分新烟碱类农药的潜在神经毒性及其潜在机制仍有待阐明。在本研究中，我们采用高通量毒性筛选平台来评估8种常用新烟碱类杀虫剂对秀丽隐杆线虫的神经毒性潜力。我们的结果表明，啶虫脒（ACE）、呋虫胺（DIN）、噻虫胺（CLO）和噻虫啉（THI）显著损害了线虫的运动行为。在研究其潜在作用机制时，我们发现ACE、CLO和THI可诱导5-羟色胺能神经元损伤，而胆碱能、多巴胺能和γ-氨基丁酸能神经元未受影响。此外，这三种新烟碱类农药主要通过增强氧化应激来降低弯曲频率，抗氧化剂N-乙酰-L-半胱氨酸可部分缓解这种情况。在神经递质系统中，ACE主要上调神经递质合成和转运相关基因的mRNA表达，而THI增加转运相关基因表达并降低γ-氨基丁酸能受体基因表达。相比之下，DIN提高了总乙酰胆碱水平，但未显著改变基因表达，表明其作用机制不同。总之，我们的研究结果表明，ACE、CLO和THI通过氧化应激和5-羟色胺能神经元损伤发挥神经毒性，而DIN主要破坏神经递质系统。我们的研究为新烟碱类农药诱导的神经毒性高通量筛选提供了见解，为未来深入研究充分阐明新烟碱类农药的毒性机制并评估其环境和健康风险提供了关键基础。
