Behavioral Effects and Potential Mechanisms of Imidacloprid- and Flupyradifurone-Induced Neurotoxicity in Caenorhabditis elegans

Abstract

Neonicotinoid insecticides raise concerns about neurotoxicity in nontarget organisms, motivating evaluation of alternatives such as flupyradifurone (FPF). We compared the neurotoxicity of imidacloprid (IMI) and FPF in Caenorhabditis elegans after 72 h exposure to 0.1–100 μg/L. Behavioral, neuronal, neurochemical, transcriptional, and oxidative-stress end points were assessed. IMI impaired locomotion more potently, with lowest observed effect concentrations of 0.1 μg/L for head thrashes and body bends, whereas corresponding FPF values were 100 and 1 μg/L, respectively. At 100 μg/L, FPF caused neurodegeneration comparable to or greater than that induced by IMI across several neuronal subtypes. IMI preferentially reduced dopamine, whereas FPF increased GABA and glutamate. Transcriptional and molecular docking analyses suggested potential disruptions in neurotransmitter synthesis, transport, signaling, and reuptake. Both insecticides increased reactive oxygen species, while transcriptional patterns suggested a comparatively weaker antioxidant response to FPF. These findings reveal distinct neurotoxic profiles and support cautious safety evaluation of replacement insecticides.