Neurotoxicity and accumulation of CPPD quinone at environmentally relevant concentrations in Caenorhabditis elegans

Abstract

"CPPD quinone (CPPDQ) is a member of PPDQs, which was widely distributed in different environments. Using Caenorhabditis elegans as an animal model, we here examined neurotoxicity and accumulation of CPPDQ and the underlying mechanism. After exposure to 0.01-10 μg/L CPPDQ, obvious body accumulation of CPDDQ was detected. Meanwhile, exposure to CPPDQ (0.01-10 μg/L) decreased head thrash, body bend, and forward turn, and increased backward turn. Nevertheless, only exposure to 10 μg/L CPPDQ induced neurodegeneration in GABAergic system. Exposure to CPPDQ (0.01-10 μg/L) further decreased expressions of daf-7 encoding TGF-β ligand, jnk-1 encoding JNK MAPK, and mpk-1 encoding ERK MAPK. Additionally, among examined G protein-coupled receptor (GPCR) genes, exposure to CPPDQ (0.01-10 μg/L) decreased dcar-1 expression and increased npr-8 expression. RNAi of daf-7, jnk-1, mpk-1, and dcar-1 resulted in susceptibility, and nhr-8 RNAi caused resistance to CPPDQ neurotoxicity and accumulation. Moreover, in CPPDQ exposed nematodes, RNAi of dcar-1 decreased jnk-1 and mpk-1 expressions, and RNAi of npr-8 increased mpk-1 expression. Therefore, exposure to CPPDQ potentially resulted in neurotoxicity by inhibiting TGF-β, JNK MAPK, and ERK MAPK signals. The inhibition in JNK MAPK and ERK MAPKs signals in CPPDQ exposed nematodes was further related to alteration in GPCRs of DCAR-1 and NHR-8 in nematodes."