Exposure to 6-PPD Quinone at Environmentally Relevant Concentrations Causes Abnormal Locomotion Behaviors and Neurodegeneration in Caenorhabditis elegans .

6-PPD quinone (6-PPDQ) can be transformed from 6-PPD through ozonation. Nevertheless, the potential neurotoxicity of 6-PPDQ after long-term exposure and the underlying mechanism are largely unclear. In , we here observed that 0.1-10 μg/L of 6-PPDQ caused several forms of abnormal locomotion behaviors. Meanwhile, the neurodegeneration of D-type motor neurons was observed in 10 μg/L of 6-PPDQ-exposed nematodes. The observed neurodegeneration was associated with the activation of the Ca channel DEG-3-mediated signaling cascade. In this signaling cascade, expressions of , , , , , and were increased by 10 μg/L of 6-PPDQ. Moreover, among genes encoding neuronal signals required for the control of stress response, expressions of and were decreased by 0.1-10 μg/L of 6-PPDQ, and expressions of and were decreased by 10 μg/L of 6-PPDQ. RNAi of , , , and resulted in the susceptibility to 6-PPDQ toxicity in decreasing locomotory ability and in inducing neurodegeneration, suggesting that JNK-1, DBL-1, DAF-7, and GLB-10 were also required for the induction of 6-PPDQ neurotoxicity. Molecular docking analysis further demonstrated the binding potential of 6-PPDQ to DEG-3, JNK-1, DBL-1, DAF-7, and GLB-10. Together, our data suggested the exposure risk of 6-PPDQ at environmentally relevant concentrations in causing neurotoxicity in organisms.