Institute of Life Science and Green Development, College of Life Science, Hebei University, Baoding, 071002, China; Hebei Basic Science Center for Biotic Interaction, Hebei University, Baoding, 071002, China.
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Shuangqing RD 18, Beijing, 100085, China.
Environ Pollut. 2024 Nov 1;360:124768. doi: 10.1016/j.envpol.2024.124768. Epub 2024 Aug 18.
The neurotoxic effects of neonicotinoids (NEOs) have been widely reported in relation to the poisoning of wild birds, yet the underlying molecular mechanism has remained elusive. This study employed Japanese quails (Coturnix japonica) and primary quail embryonic neurons as in vivo and ex vivo models, respectively, to investigate the neurotoxic effects and mechanism of thiamethoxam (TMX), a representative neonicotinoid insecticide, at environmentally relevant concentrations. Following a 28-day exposure to TMX, metabolomic analysis of quail brain revealed TMX-induced changes in glutamatergic, GABA-ergic, and dopaminergic function. Subsequent ex vivo and in silico experimentation revealed that the activation of nicotinic acetylcholine receptors and calcium signaling, induced by clothianidin (CLO), the primary metabolite of TMX, served as upstream events for the alterations in neurotransmitter synthesis, metabolism, release, and uptake. Our findings propose that the disruption of the central nervous system, caused by environmentally significant concentrations of NEOs, may account for the avian poisoning events induced by NEOs.
新烟碱类（NEOs）的神经毒性作用已被广泛报道与野生鸟类中毒有关，但潜在的分子机制仍不清楚。本研究分别采用日本鹌鹑（Coturnix japonica）和原代鹌鹑胚胎神经元作为体内和体外模型，研究噻虫嗪（TMX），一种代表性的新烟碱类杀虫剂，在环境相关浓度下的神经毒性作用和机制。在 28 天的 TMX 暴露后，对鹌鹑大脑进行代谢组学分析，发现 TMX 诱导了谷氨酸能、GABA 能和多巴胺能功能的变化。随后的离体和计算机实验表明，噻虫胺（CLO），TMX 的主要代谢物，激活烟碱型乙酰胆碱受体和钙信号，是改变神经递质合成、代谢、释放和摄取的上游事件。我们的研究结果表明，环境中显著浓度的 NEOs 对中枢神经系统的破坏可能是由 NEOs 引起的鸟类中毒事件的原因。
