Disruption of dopamine metabolism by exposure to 6-PPD quinone in Caenorhabditis elegans

Caenorhabditis elegans is a useful model for examining metabolic processes and related mechanisms. We here examined the effect of exposure to N-(1,3-dimethylbutyl)-N '-phenyl-p-phenylenediamine quinone (6-PPDQ) on dopamine metabolism and underling molecular basis in nematodes. The dopamine content was reduced by 6-PPDQ (1 and 10 mu g/L). Meanwhile, dopamine related behaviors (basal slowing response and area restricted searching) were changed by 6-PPDQ (1 and 10 mu g/L). Exposure to 6-PPDQ (1 and 10 mu g/L) decreased expressions of genes (cat-2 and bas-1) encoding enzymes governing dopamine synthesis and cat-1 encoding dopamine transporter. Development of dopaminergic neurons was also affected by 10 mu g/L 6-PPDQ as reflected by decrease in fluorescence intensity, neuronal loss, and defect in dendrite development. Exposure to 6-PPDQ (1 and 10 mu g/L) altered expressions of ast-1 and rcat-1 encoding upregulators of cat-2 and bas-1. The dopamine content and expressions of cat-2 and bas-1 were inhibited by RNAi of ast-1 and increased by RNAi of rcat-1 in 6-PPDQ exposed nematodes. Using endpoints of locomotion behavior and brood size, in 6-PPDQ exposed nematodes, the sus-ceptibility to toxicity was caused by RNAi of ast-1, cat-2, bas-1, and cat-1, and the resistance to toxicity was induced by RNAi of rcat-1. Therefore, 6-PPDQ exposure disrupted dopamine metabolism and the altered mo-lecular basis for dopamine metabolism was associated with 6-PPDQ toxicity induction. Moreover, the defects in dopamine related behaviors and toxicity on locomotion and reproduction could be rescued by treatment with 0.1 mM dopamine.

Automated summary

This study examines the effects of 6-PPDQ exposure on dopamine metabolism and related behaviors in Caenorhabditis elegans. The results show that 6-PPDQ decreases dopamine content and alters dopamine-related behaviors. It also affects the expression of genes involved in dopamine synthesis and transport. Furthermore, the study demonstrates that the altered molecular basis for dopamine metabolism is associated with 6-PPDQ-induced toxicity. Treatment with dopamine can rescue the defects in dopamine-related behaviors and toxicity.