PPARα Antagonism Rescues Chlorpyrifos-Induced Neuro-Visual Toxicity in Zebrafish (Danio rerio) Larvae

作者：Yuyao Jiang, Zijie Ding, Ruolin Hu, Jason T. Magnuson, Shiyan Li, Shiyan Li, Dingnan Wang, Shengli Zhou, Yirong Guo, Yang Wang, Yuanyuan Liu, Shuying Li, Shuying Li, Wenjun Gui · 发表于：Toxics · 年份：2026 · DOI：10.3390/toxics14030234 · 研究领域：Zebrafish Biomedical Research Applications、Environmental Toxicology and Ecotoxicology、Pesticide Exposure and Toxicity

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. C...