With the global population predicted to reach 10 billion by 2050, pesticides are essential for agricultural production. However, they can introduce chemical stressors into aquatic ecosystems. Chlorpyrifos (CPF) is a widely used organophosphate insecticide that can enter aquatic environments and poses potential risks to early-life-stage fish. Because the retina is an extension of the central nervous system and vision-guided behaviors are highly sensitive to neural dysfunction, we hypothesized that CPF exposure disrupts neurobehavioral and visual function via oxidative stress and PPARα-related signaling. Zebrafish larvae were exposed to CPF (0.01, 0.1, 1, 10, and 100 μg/L) with a vehicle control (VC). During the photomotor response assay, exposure to 100 μg/L CPF reduced overall swimming activity by 48.90% and dark-period activity by 57.71%, whereas 1 μg/L CPF modestly increased total distance by 6.96% (p = 0.003) and dark-period distance by 5.40% (p = 0.011). Transcriptomic profiling highlighted nervous- and vision-related functional categories, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment implicated pathways including gonadotropin-releasing hormone (GnRH), mitogen-activated protein kinase (MAPK), and peroxisome proliferator-activated receptor (PPAR) signaling. Targeted neurotransmitter metabolomics showed significant increases in dopamine, γ-aminobutyric acid (GABA), and acetylcholine across treatment groups, indicating broad neurotransmitter dysregulation. Consistent with these findings, neuronal fluorescence in Tg (elavl3: EGFP) larvae decreased by 12.1% and 32.5% in the 1 and 100 μg/L groups, respectively (p < 0.001), and glial fibrillary acidic protein (GFAP) immunofluorescence increased in the eye/brain/olfactory bulb at 1 μg/L (p = 0.037) and 100 μg/L (p = 0.002). Histology further showed retinal injury, with a 14.3% reduction in photoreceptor layer thickness at 100 μg/L (p = 0.034). Mechanistically, coexposure to a PPARα antagonist (GW6471) alleviated CPF-induced behavioral deficits (1.80-fold increase in dark locomotion) and reduced elevated GABA and dopamine levels by 36.8% and 47.3%, respectively. Together, these results indicate that CPF can impair neuro-visual development and that oxidative stress and PPARα-related signaling are closely associated with these effects.
Jiang et al. (Mon,) studied this question.