2,4,6-trinitrotoluene induces neurotoxicity by affecting the G protein pathways in Caenorhabditis elegans

2,4,6-trinitrotoluene (TNT) is a chemical widely used to make explosives, and its use of residues can lead to potential threats to both ecosystems and human health. A thorough understanding of the various toxic effects of TNT is essential for developing effective environmental protection and health safety measures. Thus, we employed Caenorhabditis elegans (C. elegans), a typical model organism, to explore the neurotoxic effects of TNT and the signaling pathways involved. The results showed that neurotoxicity induced by 10–100 ng/mL TNT was manifested in reduced behavioral capacity (head thrashes, body bends, and pharyngeal pumping rates), and inhibition of foraging behavior and ethanol avoidance behavior. Using fluorescence-labeled transgenic nematodes, it was found that TNT damaged dopaminergic and cholinergic neurons, which resulted in a significant decrease in the release of neurotransmitters and the expression of associated genes (dat-1 and unc-17). We studied the role of G protein signaling pathways and discovered that the related genes (egl-30, gsa-1, goa-1, and unc-13) were significantly down-regulated, resulting in reduced acetylcholine release, which in turn corresponded to the observed behavioral abnormality and damaged neurons in the worms. This study shed light on TNT’s neurotoxic mechanisms and associated health risks.