{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:52:33Z","timestamp":1792252353935,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["01\u201001\u201018\u20102026FR\u20105540151"],"award-info":[{"award-number":["01\u201001\u201018\u20102026FR\u20105540151"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560\u2009\u03bcM) at 5\u2009h post fertilization (hpf) to 120\u2009hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120\u2009hpf, following the exposure termination. Basic locomotor responses and anxiety\u2010like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose\u2010dependent manner (<jats:italic>p<\/jats:italic>\u2009\u2264\u2009.05). At the selected non\u2010teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA\u2010treated fish compared to the control (<jats:italic>p<\/jats:italic>\u2009\u2265\u2009.005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels.<\/jats:p>","DOI":"10.1002\/bdr2.2227","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T04:23:25Z","timestamp":1690604605000},"page":"1475-1485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Toxicity and teratogenicity effects of valproic acid on zebrafish (<i>Danio rerio<\/i>) embryos in relation to autism spectrum disorder"],"prefix":"10.1002","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5288-5731","authenticated-orcid":false,"given":"Nur Atikah","family":"Saleh Hodin","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science Universiti Putra Malaysia  Serdang Malaysia"},{"name":"Natural Medicines and Products Research Laboratory, 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