{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:50:40Z","timestamp":1785329440857,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["21877039"],"award-info":[{"award-number":["21877039"]}]},{"name":"National Natural Science Foundation of China","award":["32072441"],"award-info":[{"award-number":["32072441"]}]},{"name":"National Natural Science Foundation of China","award":["2017-01-07-00-02-E00037"],"award-info":[{"award-number":["2017-01-07-00-02-E00037"]}]},{"name":"National Natural Science Foundation of China","award":["2018YFD0200100"],"award-info":[{"award-number":["2018YFD0200100"]}]},{"name":"Innovation Program of Shanghai Municipal Education Commission","award":["21877039"],"award-info":[{"award-number":["21877039"]}]},{"name":"Innovation Program of Shanghai Municipal Education Commission","award":["32072441"],"award-info":[{"award-number":["32072441"]}]},{"name":"Innovation Program of Shanghai Municipal Education Commission","award":["2017-01-07-00-02-E00037"],"award-info":[{"award-number":["2017-01-07-00-02-E00037"]}]},{"name":"Innovation Program of Shanghai Municipal Education Commission","award":["2018YFD0200100"],"award-info":[{"award-number":["2018YFD0200100"]}]},{"name":"National Key Research and Development Program of China","award":["21877039"],"award-info":[{"award-number":["21877039"]}]},{"name":"National Key Research and Development Program of China","award":["32072441"],"award-info":[{"award-number":["32072441"]}]},{"name":"National Key Research and Development Program of China","award":["2017-01-07-00-02-E00037"],"award-info":[{"award-number":["2017-01-07-00-02-E00037"]}]},{"name":"National Key Research and Development Program of China","award":["2018YFD0200100"],"award-info":[{"award-number":["2018YFD0200100"]}]},{"name":"Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism","award":["21877039"],"award-info":[{"award-number":["21877039"]}]},{"name":"Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism","award":["32072441"],"award-info":[{"award-number":["32072441"]}]},{"name":"Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism","award":["2017-01-07-00-02-E00037"],"award-info":[{"award-number":["2017-01-07-00-02-E00037"]}]},{"name":"Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism","award":["2018YFD0200100"],"award-info":[{"award-number":["2018YFD0200100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Spinetoram is an important semi-synthetic insecticide extensively applied in agriculture. It is neurotoxic to insects, primarily by acting on acetylcholine receptors (nAChRs). However, few studies have examined the neurotoxicity of spinetoram in human beings. In this study, various concentrations (5, 10, 15, and 20 \u03bcM) of spinetoram were employed to expose SH-SY5Y cells in order to study the neurotoxic effects of spinetoram. The results showed that spinetoram exposure markedly inhibited cell viability and induced oxidative stress. It also induced mitochondrial membrane potential collapse (\u0394\u03a8m), and then caused a massive opening of the mitochondrial permeability transition pore (mPTP), a decrease in ATP synthesis, and Ca2+ overloading. Furthermore, spinetoram exposure induced cellular autophagy, as evidenced by the formation of autophagosomes, the conversion of LC3-I into LC3-II, down-regulation of p62, and up-regulation of beclin-1. In addition, we observed that p-mTOR expression decreased, while p-AMPK expression increased when exposed to spinetoram, indicating spinetoram triggered AMPK\/mTOR-mediated autophagy. Complementarily, the effect of spinetoram on neurobehavior was studied using the zebrafish model. After being exposed to different concentrations (5, 10, and 20 \u03bcg\/mL) of spinetoram, zebrafish showed neurobehavioral irregularities, such as reduced frequency of tail swings and spontaneous movements. Similarly, autophagy was also observed in zebrafish. In conclusion, spinetoram exposure produced potential neurotoxicity through autophagy mediated by mitochondrial damage. The experimental data and results of the neurotoxicity study of spinetoram provided above are intended to serve as reference for its safety assessment.<\/jats:p>","DOI":"10.3390\/molecules29010253","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T05:50:38Z","timestamp":1704261038000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Spinetoram-Induced Potential Neurotoxicity through Autophagy Mediated by Mitochondrial Damage"],"prefix":"10.3390","volume":"29","author":[{"given":"Fan","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwu","family":"Yang","sequence":"additional","affiliation":[{"name":"Frog Prince (Fujian) Baby&Child Care Product Co., Ltd., Zhangzhou 363000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenping","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Ugel Cosmetics PTE Ltd., Singapore 349561, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6804-1840","authenticated-orcid":false,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"ref_1","unstructured":"Saravi, S.S.S., and Shokrzadeh, M. 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