Inhibition of acetylcholinesterase by either organophosphates or carbamates causes anti-cholinesterase poisoning. This arises through a wide range of neurotoxic effects triggered by the overstimulation of the cholinergic receptors at synapses and neuromuscular junctions. Without intervention, this poisoning can lead to profound toxic effects, including death, and the incomplete efficacy of the current treatments, particularly for oxime-insensitive agents, provokes the need to find better antidotes. Here we show how the non-parasitic nematode Caenorhabditis elegans offers an excellent tool for investigating the acetylcholinesterase intoxication. The C. elegans neuromuscular junctions show a high degree of molecular and functional conservation with the cholinergic transmission that operates in the autonomic, central and neuromuscular synapses in mammals. In fact, the anti-cholinesterase intoxication of the worm’s body wall neuromuscular junction has been unprecedented in understanding molecular determinants of cholinergic function in nematodes and other organisms. We extend the use of the model organism’s feeding behaviour as a tool to investigate carbamate and organophosphate mode of action. We show that inhibition of the cholinergic-dependent rhythmic pumping of the pharyngeal muscle correlates with the inhibition of the acetylcholinesterase activity caused by aldicarb, paraoxons and DFP exposure. Further, this bio-assay allows one to address oxime dependent reversal of cholinesterase inhibition in the context of whole organism recovery. Interestingly, the recovery of the pharyngeal function after such anti-cholinesterase poisoning represents a sensitive and easily quantifiable phenotype that is indicative of the spontaneous recovery or irreversible modification of the worm acetylcholinesterase after inhibition. These observations highlight the pharynx of C. elegans as a new tractable approach to explore anti-cholinesterase intoxication and recovery with the potential to resolve critical genetic determinants of these neurotoxins’ mode of action.

有机磷酸酯或氨基甲酸酯对乙酰胆碱酯酶的抑制会导致抗胆碱酯酶中毒。这是由于突触和神经肌肉接头处胆碱能受体的过度刺激引起的广泛的神经毒性作用引起的。如果不进行干预，这种中毒会导致严重的毒性作用，包括死亡，目前治疗的不完全疗效，尤其是对肟不敏感的药物，需要寻找更好的解毒剂。在这里，我们展示了非寄生线虫秀丽隐杆线虫如何为研究乙酰胆碱酯酶中毒提供了极好的工具。该线虫神经肌肉接头显示出高度的分子和功能保守性，胆碱能传递在哺乳动物的自主神经、中枢和神经肌肉突触中起作用。事实上，蠕虫体壁神经肌肉接头的抗胆碱酯酶中毒在了解线虫和其他生物胆碱能功能的分子决定因素方面是前所未有的。我们将模式生物的摄食行为扩展为研究氨基甲酸盐和有机磷作用模式的工具。我们表明抑制胆碱能依赖的咽部肌肉节律性泵送与抑制由涕灭威、对氧磷和 DFP 暴露引起的乙酰胆碱酯酶活性相关。更远，这种生物测定允许在整个生物体恢复的背景下解决肟依赖性逆转胆碱酯酶抑制的问题。有趣的是，这种抗胆碱酯酶中毒后咽部功能的恢复代表了一种敏感且易于量化的表型，表明抑制后蠕虫乙酰胆碱酯酶的自发恢复或不可逆修饰。这些观察结果突出了咽秀丽隐杆线虫作为一种新的易于处理的方法来探索抗胆碱酯酶中毒和恢复，有可能解决这些神经毒素作用方式的关键遗传决定因素。