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However, whether ketamine can induce apoptosis in developing neurons remains poorly understood, largely because of the lack of effective in\u00a0vivo tools to sensitively detect transient neuronal apoptosis. In the present study, we developed sensor zebrafish that allow in\u00a0vivo apoptosis sensing and high\u2010throughput behavioral tracking to study the neurodevelopmental toxicity of ketamine. By stably expressing a genetically encoded fluorescence resonance energy transfer (FRET)\u2010based biosensor in the nervous system, we achieved highly sensitive detection of neuronal apoptosis in live zebrafish. The sensor zebrafish enabled spatiotemporal detection of transient neuronal apoptosis, which is often missed by traditional methods. Using the sensor zebrafish, we found that long\u2010term (48 and 72\u2009h) exposure to micromolar (50 and 100\u2009\u03bcM) ketamine induced discrete yet consistent apoptosis of developing neurons at the dorsal edge of the spinal cord, where primary sensory neurons and interneurons are localized. To evaluate functional deficits following the loss of these neurons, we performed high\u2010throughput swimming tracking analysis. The sensor zebrafish showed reductions in maximum acceleration and velocity after ketamine exposure. This sensor zebrafish platform provides new insights into the neurotoxicity of ketamine in the developing nervous system.<\/jats:p>","DOI":"10.1002\/jat.70438","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:52:06Z","timestamp":1789188726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prolonged Micromolar Ketamine Exposure Induces Dorsal Spinal Neuron Apoptosis and Locomotor Deficits During Early Development: Insights From FRET\u2010Based Sensor Zebrafish"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4710-5689","authenticated-orcid":false,"given":"Hao","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences University of Macau  Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences University of Macau  Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences University of Macau  Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8847-7254","authenticated-orcid":false,"given":"Renfei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences University of Macau  Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy Qian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences University of Macau  Macao SAR China"},{"name":"Ministry of Education Frontiers Science Center for Precision Oncology University of Macau  Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1207"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.11.040"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.02.012"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.201500258"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e3182860fc9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACO.0000000000000916"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibneur.2024.01.005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19\u201009\u201003277.1999"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000006897"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeq169"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.033"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010025\u201009421\u2010w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000000714"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600710516"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0432"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00784"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181ed09a2"},{"issue":"2","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1213\/00000539-198202000-00004","article-title":"Plasma Levels of Ketamine and Two of Its Metabolites in Surgical Patients Using a Gas Chromatographic Mass Fragmentographic Assay","volume":"61","author":"Domino E. 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