Exposure to low-dose nanopolystyrene induces the response of neuronal JNK MAPK signaling pathway in nematode Caenorhabditis elegans

Abstract

Background: The response of organisms to nanoplastic exposure has gradually received the attention. Nevertheless, the role of neurons in response to nanoplastic exposure and the underlying mechanism are still largely unclear. We here examined the role of neuronal JNK MAPK signaling in response to low-dose of polystyrene (100 nm) in Caenorhabditis elegans. Results: Exposure to nanopolystyrene in the range of μg/L could increase the expression of genes (jkk-1, mek-1, and jnk-1) encoding JNK MAPK signaling pathway. Meanwhile, RNAi knockdown of any of these genes induced a susceptibility to nanopolystyrene toxicity. In the neurons, SNB-1/synaptobrevin was identified as the downstream target of JNK-1/JNK, suggesting the alteration in neurotransmitter signals in nanopolystyrene-exposed nematodes. In nanopolystyrene-exposed nematodes, JNK-1 modulated TBH-1-mediated octopamine signal and CAT-2-mediated dopamine signal. TBH-1 and CAT-2 further regulated the response to nanopolystyrene by affecting the function of corresponding intestinal octopamine receptors (SER-6 and OCTR-1) and intestinal dopamine receptor (DOP-1). In the intestine, DOP-1 regulated the response to nanopolystyrene by activating the downstream signaling cascade in p38 MAPK signaling pathway. Conclusions: Exposure to low-dose of nanopolystyrene could induce the response of neuronal JNK MAPK signaling pathway in nematodes. Our data further highlight the crucial role of neuronal JNK MAPK signaling-activated alteration in octopamine and dopamine signals in regulating the response to nanopolystyrene in organisms.

Microplastics and Their Impact on Reproduction—Can we Learn From the C. elegans Model?

“…The exposure to UV-aged PS-MPs caused more severe dopaminergic defects than virgin MPs, probably due to the leaching of toxic materials ( Chen et al, 2021a ). Interestingly, PS-NP exposure in C. elegans causes significant increase in the expression level of intestinal dop-1 , a gene encoding for a dopamine receptor ( Qu et al, 2020a ), further supporting the idea of MP-driven interference with the dopaminergic system in nematodes.…”

Induction of Protective Response Associated with Expressional Alterations in Neuronal G Protein-Coupled Receptors in Polystyrene Nanoparticle Exposed Caenorhabditis elegans

“…In C. elegans , JNK MAPK/JNK-1 signaling acted in the neurons to control the PS-NPs toxicity by modulating neurotransmissions of octopamine and dopamine between neurons and intestine . In PS-NPs exposed worms, neuronal RNAi knockdown of npr-9 , npr-12 , or gtr-1 increased the jnk-1 expression, and neuronal RNAi knockdown of dcar-1 decreased the jnk-1 expression (Figure S4).…”

“…In neuronal cells, we found that the GPCRs of NPR-9, NPR-12, DCAR-1, and GTR-1 functioned upstream of JNK MAPK signaling to control PS-NPs toxicity (Figure and Table S4). Considering that the neuronal JNK MAPK/JNK-1 controlled PS-NPs toxicity by regulating neurotransmission of octopamine and dopamine from neuronal cells to intestinal cells, these four neuronal GPCRs had the potential to modulate the neurotransmission of octopamine and dopamine in PS-NPs exposed nematodes. Therefore, besides the oxidative stress related signaling pathways, some other signaling pathways (such as JNK MAPK signaling pathway) might be also affected by neuronal GPCRs so as to induce the alterations in some end points (such as locomotion behavior) in PS-NPs exposed nematodes.…”

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

“…84,85 Moreover, JNK-1 and DBL-1 could function in the neurons to control the toxicity of polystyrene nanoparticles. 71,73 Moreover, we found that expressions of daf-7 encoding another TGF-β ligand and glb-10 encoding a globin could also be decreased by 10 μg/L of 6-PPDQ (Figure 4A). In addition, the susceptibility to 6-PPDQ neurotoxicity on locomotion behaviors could also be detected in daf-7(RNAi) and glb-10(RNAi) nematodes (Figure S3).…”