biostudies-literatureAbu Bakar NUniversiti Putra MalaysiaMinistry of Higher Education, Malaysia, under the Transdisciplinary-Fundamental Research Grant Scheme (TRGS)Universiti Putra Malaysia under the Putra Grant SchemeMinistry of Higher EducationKorean Ministry of Environment (MOE)Fundamental Research Grant Scheme (FRGS)Ministry of Environment493https://www.ebi.ac.uk/biostudies/studies/S-EPMC9502072biostudies-literatureUnknown10(9)Arsenic trioxide (As₂O₃) is a ubiquitous heavy metal in the environment. Exposure to this toxin at low concentrations is unremarkable in developing organisms. Nevertheless, understanding the underlying mechanism of its long-term adverse effects remains a challenge. In this study, embryos were initially exposed to As₂O₃ from gastrulation to hatching under semi-static conditions. Results showed dose-dependent increased mortality, with exposure to 30-40 µM As₂O₃ significantly reducing tail-coiling and heart rate at early larval stages. Surviving larvae after 30 µM As₂O₃ exposure showed deficits in motor behavior without impairment of anxiety-like responses at 6 dpf and a slight impairment in color preference behavior at 11 dpf, which was later evident in adulthood. As₂O₃ also altered locomotor function, with a loss of directional and color preference in adult zebrafish, which correlated with changes in transcriptional regulation of <i>adsl</i>, <i>shank3a</i>, and <i>tsc1b</i> genes. During these processes, As₂O₃ mainly induced metabolic changes in lipids, particularly arachidonic acid, docosahexaenoic acid, prostaglandin, and sphinganine-1-phosphate in the post-hatching period of zebrafish. Overall, this study provides new insight into the potential mechanism of arsenic toxicity leading to long-term learning impairment in zebrafish and may benefit future risk assessments of other environmental toxins of concern.ToxicsEmbryonic Arsenic Exposure Triggers Long-Term Behavioral Impairment with Metabolite Alterations in Zebrafish.PMC9502072UPM/700-2/1/GP/2017/9550900FRGS/1/2018/STG03/UPM/02/2RE2021003310003TD-FRGS/2/2013/UPM/02/1/3Abu Bakar NMediani AKim CHRamlan NFChe Abdullah CAWan Ibrahim WNNasruddin NSShaari KShohaimi SMohd Faudzi SMfalseEmbryonic Arsenic Exposure Triggers Long-Term Behavioral Impairment with Metabolite Alterations in Zebrafish.Arsenic trioxide (As₂O₃) is a ubiquitous heavy metal in the environment. Exposure to this toxin at low concentrations is unremarkable in developing organisms. Nevertheless, understanding the underlying mechanism of its long-term adverse effects remains a challenge. In this study, embryos were initially exposed to As₂O₃ from gastrulation to hatching under semi-static conditions. Results showed dose-dependent increased mortality, with exposure to 30-40 µM As₂O₃ significantly reducing tail-coiling and heart rate at early larval stages. Surviving larvae after 30 µM As₂O₃ exposure showed deficits in motor behavior without impairment of anxiety-like responses at 6 dpf and a slight impairment in color preference behavior at 11 dpf, which was later evident in adulthood. As₂O₃ also altered locomotor function, with a loss of directional and color preference in adult zebrafish, which correlated with changes in transcriptional regulation of <i>adsl</i>, <i>shank3a</i>, and <i>tsc1b</i> genes. During these processes, As₂O₃ mainly induced metabolic changes in lipids, particularly arachidonic acid, docosahexaenoic acid, prostaglandin, and sphinganine-1-phosphate in the post-hatching period of zebrafish. Overall, this study provides new insight into the potential mechanism of arsenic toxicity leading to long-term learning impairment in zebrafish and may benefit future risk assessments of other environmental toxins of concern.2022-01-01T00:00:00Z2022 Aug2026-06-20T03:24:29.134Z2025-04-07T08:59:09.704ZS-EPMC95020723613645810.3390/toxics10090493