{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:14:07Z","timestamp":1792790047199,"version":"4.5.0"},"reference-count":79,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial \u2018Lingyan\u2019 Research and Development Program","award":["2023C02039"],"award-info":[{"award-number":["2023C02039"]}]},{"name":"Core Facilities, Zhejiang University School of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>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 PPAR\u03b1-related signaling. Zebrafish larvae were exposed to CPF (0.01, 0.1, 1, 10, and 100 \u03bcg\/L) with a vehicle control (VC). During the photomotor response assay, exposure to 100 \u03bcg\/L CPF reduced overall swimming activity by 48.90% and dark-period activity by 57.71%, whereas 1 \u03bcg\/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, \u03b3-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 \u03bcg\/L groups, respectively (p &lt; 0.001), and glial fibrillary acidic protein (GFAP) immunofluorescence increased in the eye\/brain\/olfactory bulb at 1 \u03bcg\/L (p = 0.037) and 100 \u03bcg\/L (p = 0.002). Histology further showed retinal injury, with a 14.3% reduction in photoreceptor layer thickness at 100 \u03bcg\/L (p = 0.034). Mechanistically, coexposure to a PPAR\u03b1 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 PPAR\u03b1-related signaling are closely associated with these effects.<\/jats:p>","DOI":"10.3390\/toxics14030234","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T13:27:18Z","timestamp":1773062838000},"page":"234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PPAR\u03b1 Antagonism Rescues Chlorpyrifos-Induced Neuro-Visual Toxicity in Zebrafish (Danio rerio) Larvae"],"prefix":"10.3390","volume":"14","author":[{"given":"Yuyao","family":"Jiang","sequence":"first","affiliation":[{"name":"Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijie","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolin","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6841-8014","authenticated-orcid":false,"given":"Jason T.","family":"Magnuson","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences, University of California, Riverside, Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyan","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang Fisheries Technical Extension Center, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingnan","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Fisheries Technical Extension Center, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengli","family":"Zhou","sequence":"additional","affiliation":[{"name":"Ecological and Environmental Monitoring Center of Zhejiang Province, Hangzhou 310012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5262-1675","authenticated-orcid":false,"given":"Yirong","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Fisheries Technical Extension Center, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0786-5931","authenticated-orcid":false,"given":"Shuying","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China"},{"name":"Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insects, Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insect Pests, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Gui","sequence":"additional","affiliation":[{"name":"Institute of Pesticide and Environmental Toxicology, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","unstructured":"Food and Agriculture Organization of the United Nations (2025). 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