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We compared the neurotoxicity of imidacloprid (IMI) and FPF in Caenorhabditis elegans after 72 h exposure to 0.1\u2013100 \u03bcg\/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 \u03bcg\/L for head thrashes and body bends, whereas corresponding FPF values were 100 and 1 \u03bcg\/L, respectively. At 100 \u03bcg\/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.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05811","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T02:01:39Z","timestamp":1786154499000},"page":"25619-25628","source":"Crossref","is-referenced-by-count":0,"title":["Behavioral Effects and Potential Mechanisms of Imidacloprid-\nand Flupyradifurone-Induced Neurotoxicity in\n                    <i>Caenorhabditis elegans<\/i>"],"prefix":"10.1021","volume":"74","author":[{"given":"Xingang","family":"Hou","sequence":"first","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Agricultural University , , ,","place":["Jinzhong, China, 030801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Zheng","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Ma","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wei","sequence":"additional","affiliation":[{"name":"Jilin Agricultural University , , ,","place":["Changchun, China, 130118"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Hou","sequence":"additional","affiliation":[{"name":"Jilin Agricultural University , , ,","place":["Changchun, China, 130118"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-6789","authenticated-orcid":true,"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-8421","authenticated-orcid":true,"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai University , , ,","place":["Shanghai, China, 200444"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9275-6713","authenticated-orcid":true,"given":"Fanrong","family":"Zhao","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Han","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026081910160660100_cit1","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1146\/annurev-ento-020117-043042","article-title":"Neonicotinoids\nand Other Insect Nicotinic Receptor Competitive Modulators: Progress\nand Prospects","volume":"63","author":"Casida","year":"2018","journal-title":"Annu. 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Total Environ."},{"issue":"9","key":"2026081910160660100_cit41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238637","article-title":"Neonicotinoid-Containing\nInsecticide Disruption of Growth, Locomotion, and Fertility in Caenorhabditis Elegans","volume":"15","author":"Bradford","year":"2020","journal-title":"PLoS One"},{"key":"2026081910160660100_cit42","doi-asserted-by":"publisher","first-page":"105913","DOI":"10.1016\/j.aquatox.2021.105913","article-title":"Imidacloprid Induces\nLocomotion Impairment of the Freshwater\nCrayfish, Procambarus Clarkii via Neurotoxicity and Oxidative Stress\nin Digestive System","volume":"238","author":"Huang","year":"2021","journal-title":"Aquat. Toxicol."},{"issue":"11","key":"2026081910160660100_cit43","doi-asserted-by":"publisher","first-page":"696","DOI":"10.3390\/toxics10110696","article-title":"Detection\nof Changes in Monoamine Neurotransmitters by the Neonicotinoid Pesticide\nImidacloprid Using Mass Spectrometry","volume":"10","author":"Hirai","year":"2022","journal-title":"Toxics"},{"issue":"51","key":"2026081910160660100_cit44","doi-asserted-by":"publisher","first-page":"13513","DOI":"10.1021\/acs.jafc.8b05793","article-title":"Imidacloprid\nImpacts on Neurobehavioral\nPerformance, Oxidative Stress, and Apoptotic Events in the Brain of\nAdolescent and Adult Rats","volume":"66","author":"Abd-Elhakim","year":"2018","journal-title":"J. Agric. 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Elegans: Oxidative\nStress and Serotonergic Neuronal Damage\nas Key Mechanisms","volume":"383","author":"Wu","year":"2025","journal-title":"Environ. 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