{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:21:03Z","timestamp":1793298063006,"version":"4.5.0"},"reference-count":74,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"publisher","award":["SWHX-202503"],"award-info":[{"award-number":["SWHX-202503"]}],"id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2018M640640"],"award-info":[{"award-number":["2018M640640"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009108","name":"Shandong University","doi-asserted-by":"publisher","award":["2017GN0030"],"award-info":[{"award-number":["2017GN0030"]}],"id":[{"id":"10.13039\/100009108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21906095"],"award-info":[{"award-number":["21906095"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2019BB018"],"award-info":[{"award-number":["ZR2019BB018"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jinan Microecological Biomedicine Shandong Laboratory","award":["JNL-2023002KF"],"award-info":[{"award-number":["JNL-2023002KF"]}]},{"name":"Digital Fujian Institute of Big Data for Elderly Rehabilitation and Nursing","award":["BDRI202502"],"award-info":[{"award-number":["BDRI202502"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Artificial sweeteners are widely consumed, yet their potential neurotoxic effects remain poorly understood. Using sucralose (SUC) as a model compound, this study develops an approach to rapidly screen the neurotoxicity of artificial sweeteners and explore their potential associations with neurodegenerative-like processes, especially Alzheimer\u2019s disease (AD)-like phenotypes. SUC is minimally absorbed and metabolized by mammals, leading to its widespread presence in the environment. Here, we integrate high-throughput behavioral phenotyping in larval zebrafish with targeted analyses in adult and AD transgenic models, employing a \u201cbehavioral phenoblast\u201d strategy adapted from prior large-scale sleep-wake drug screens. SUC effects were evaluated across a broad concentration range (5 \u03bcg\/L to 100 mg\/L), covering low-dose to high-dose exposure conditions. Hierarchical and K-means clustering revealed that SUC\u2019s behavioral signatures closely resembled those of compounds associated with neurodegenerative risks. To validate these findings, adult zebrafish were exposed to SUC within the Acceptable Daily Intake (ADI) range (1\u2013100 mg\/L) for 3 months, resulting in dose-dependent increases in anxiety-like behaviors and impairments in learning and memory. Notably, treatment of transgenic zebrafish expressing human misfolded A\u03b2 protein with SUC exacerbated A\u03b2-related pathological phenotypes in a dose-dependent manner. These findings highlight the need for further investigation into the long-term neurological impacts of artificial sweeteners and provide a methodological framework for evaluating the potential health risks of artificial sweeteners.<\/jats:p>","DOI":"10.1021\/acsomega.6c04972","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:18:13Z","timestamp":1788430693000},"page":"54169-54186","source":"Crossref","is-referenced-by-count":1,"title":["Sucralose Induces\nNeurobehavioral Alterations and\nExacerbates Alzheimer\u2019s Disease-Like Phenotypes in Zebrafish\nModels"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-1713","authenticated-orcid":true,"given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"Shandong University , , ,","place":["Jinan, China, 250012"]},{"name":"Yunnan Bainian Boya Science and Technology Innovation Co., Ltd. , ,","place":["Kunming, China, 650000"]},{"name":"Jinan Microecological Biomedicine Shandong Laboratory , ,","place":["Jinan, China, 250118"]},{"name":"Nankai University , , ,","place":["Tianjin, China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7480-8977","authenticated-orcid":true,"given":"Zhuang","family":"Miao","sequence":"additional","affiliation":[{"name":"Shandong University , , ,","place":["Jinan, China, 250012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiying","family":"Bi","sequence":"additional","affiliation":[{"name":"Shandong University , , ,","place":["Jinan, China, 250012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ningde Normal University , , ,","place":["Ningde, China, 352100"]},{"name":"Digital Fujian Research Institute of Big Data for Elderly Rehabilitation and Nursing , ,","place":["Ningde, China, 352100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Ningde Normal University , , ,","place":["Ningde, China, 352100"]},{"name":"Digital Fujian Research Institute of Big Data for Elderly Rehabilitation and Nursing , ,","place":["Ningde, China, 352100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"issue":"4","key":"2026091510093849700_cit1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/oby.22139","article-title":"Nonnutritive Sweeteners\nin Weight Management and Chronic\nDisease: A Review","volume":"26","author":"Sylvetsky","year":"2018","journal-title":"Obesity"},{"key":"2026091510093849700_cit2","unstructured":"Browning, L.\n          \n          Makers of Artificial\nSweeteners Go to Court. New York Times, 2007. https:\/\/www.nytimes.com\/2007\/04\/06\/business\/media\/06sweet.html."},{"issue":"2","key":"2026091510093849700_cit3","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1541-4337.2006.tb00081.x","article-title":"Low-Calorie\nSweeteners and Other\nSugar Substitutes: A Review of the Safety Issues","volume":"5","author":"Kroger","year":"2006","journal-title":"Compr. Rev. Food Sci. Food Saf"},{"issue":"7","key":"2026091510093849700_cit4","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/10937404.2013.842523","article-title":"Sucralose, a Synthetic\nOrganochlorine Sweetener: An\nOverview of Biological Issues","volume":"16","author":"Schiffman","year":"2013","journal-title":"J. Toxicol. Environ.\nHealth, Part B"},{"issue":"2","key":"2026091510093849700_cit5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0278-6915(00)00034-X","article-title":"The Metabolic\nFate\nof Sucralose in Rats","volume":"38","author":"Sims","year":"2000","journal-title":"Food Chem. Toxicol"},{"issue":"Suppl 2","key":"2026091510093849700_cit6","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1016\/S0278-6915(00)00026-0","article-title":"Sucralose metabolism\nand pharmacokinetics in man","volume":"38","author":"Roberts","year":"2000","journal-title":"Food Chem. Toxicol"},{"issue":"20","key":"2026091510093849700_cit7","doi-asserted-by":"publisher","first-page":"8716","DOI":"10.1021\/es202404c","article-title":"Artificial\nsweetener Sucralose in U.S. drinking water systems","volume":"45","author":"Mawhinney","year":"2011","journal-title":"Environ. Sci. 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Mater"},{"issue":"7521","key":"2026091510093849700_cit9","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nature13793","article-title":"Artificial\nSweeteners Induce Glucose Intolerance by\nAltering the Gut Microbiota","volume":"514","author":"Suez","year":"2014","journal-title":"Nature"},{"issue":"1","key":"2026091510093849700_cit10","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.cmet.2016.06.010","article-title":"Sucralose Promotes Food Intake through\nNPY and a Neuronal Fasting Response","volume":"24","author":"Wang","year":"2016","journal-title":"Cell Metab"},{"issue":"9","key":"2026091510093849700_cit11","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.2337\/dc12-2221","article-title":"Sucralose\nAffects Glycemic and Hormonal Responses to an Oral Glucose Load","volume":"36","author":"Pepino","year":"2013","journal-title":"Diabetes Care"},{"issue":"8","key":"2026091510093849700_cit12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161264","article-title":"Effects of the Non-Nutritive Sweeteners\non Glucose Metabolism and Appetite Regulating Hormones: Systematic\nReview of Observational Prospective Studies and Clinical Trials","volume":"11","author":"Romo-Romo","year":"2016","journal-title":"PLoS One"},{"issue":"21","key":"2026091510093849700_cit13","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1080\/15287390802328630","article-title":"Splenda\nAlters Gut Microflora and Increases Intestinal P-Glycoprotein and\nCytochrome P-450 in Male Rats","volume":"71","author":"Abou-Donia","year":"2008","journal-title":"J. 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