{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:07:03Z","timestamp":1785582423178,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Brescia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As most new medications, Cabotegravir (CAB) was recently approved as an antiretroviral treatment of HIV infection without in-depth safety information on in utero exposure. Although no developmental toxicity in rats and rabbits was reported, recent studies demonstrated that CAB decreases pluripotency of human embryonic stem cells. CAB exposure effects during development were assessed in zebrafish embryos by the Fish Embryo Toxicity test after exposure at subtherapeutic concentrations up to 25\u00d7 the human Cmax. Larvae behavior was assessed by the light\u2013dark locomotion test. The expression of factors involved in neurogenesis was evaluated by whole-mount in situ hybridization. CAB did not cause gross morphological defects at low doses, although pericardial edema, uninflated swim bladder, decreased heartbeats, growth delay, and decreased hatching rate were observed at the highest concentrations. Decreased locomotion was observed even at the subtherapeutic dose, suggesting alterations of nervous system integrity. This hypothesis was supported by the observation of decreased expression of crucial factors involved in early neuronal differentiation in diencephalic and telencephalic dopaminergic areas, midbrain\/hindbrain boundary, and craniofacial ganglia. These findings support CAB effects on neurogenesis in zebrafish embryos and suggest long-term follow-up of exposed infants to provide data on drug safety during pregnancy.<\/jats:p>","DOI":"10.3390\/ijms24031994","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T05:50:20Z","timestamp":1674107420000},"page":"1994","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cabotegravir Exposure of Zebrafish (Danio rerio) Embryos Impacts on Neurodevelopment and Behavior"],"prefix":"10.3390","volume":"24","author":[{"given":"Daniela","family":"Zizioli","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3902-3376","authenticated-orcid":false,"given":"Isabella","family":"Zanella","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"},{"name":"Clinical Chemistry Laboratory, Cytogenetics and Molecular Genetics Section, Diagnostic Department, ASST Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-1225","authenticated-orcid":false,"given":"Luca","family":"Mignani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Degli Antoni","sequence":"additional","affiliation":[{"name":"Division of Infectious and Tropical Diseases, ASST Spedali Civili di Brescia, 25123 Brescia, Italy"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Castelli","sequence":"additional","affiliation":[{"name":"Division of Infectious and Tropical Diseases, ASST Spedali Civili di Brescia, 25123 Brescia, Italy"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1452-9100","authenticated-orcid":false,"given":"Eugenia","family":"Quiros-Roldan","sequence":"additional","affiliation":[{"name":"Division of Infectious and Tropical Diseases, ASST Spedali Civili di Brescia, 25123 Brescia, Italy"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","first-page":"157","article-title":"Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: Evidence to date","volume":"8","author":"Whitfield","year":"2016","journal-title":"HIV AIDS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3109\/00498254.2015.1081993","article-title":"Drug interaction profile of the HIV integrase inhibitor cabotegravir: Assessment from in vitro studies and a clinical investigation with midazolam","volume":"46","author":"Reese","year":"2016","journal-title":"Xenobiotica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1124\/dmd.112.048918","article-title":"In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor","volume":"41","author":"Reese","year":"2013","journal-title":"Drug Metab. 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