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Here, we tested the hypothesis that by inhibiting brain development, larval exposure to severe hypoxia has persistent functional effects on the cortisol stress response in zebrafish (Danio rerio). Exposing 5\u2005days post-fertilization (dpf) larvae to 10% dissolved O2 (DO) for 16\u2005h only marginally reduced survival, but it decreased forebrain neural proliferation by 55%, and reduced the expression of neurod1, gfap and mbpa, markers of determined neurons, glia and oligodendrocytes, respectively. The 5\u00a0dpf hypoxic exposure also elicited transient increases in whole-body cortisol and in crf, uts1 and hsd20b2 expression, key regulators of the endocrine stress response. Hypoxia exposure at 5\u00a0dpf also inhibited the cortisol stress response to hypoxia in 10\u00a0dpf larvae and increased hypoxia tolerance. However, 10% DO exposure at 5\u00a0dpf for 16\u2005h did not affect the cortisol stress response to a novel stressor in 10\u00a0dpf larvae or the cortisol stress response to hypoxia in adult fish. Therefore, while larval exposure to severe hypoxia can inhibit brain development, it also increases hypoxia tolerance. These effects may transiently reduce the impact of hypoxia on the cortisol stress response but not its functional capacity to respond to novel stressors. We conclude that the larval cortisol stress response in zebrafish has a high capacity to cope with severe hypoxia-induced neurogenic impairment.<\/jats:p>","DOI":"10.1242\/jeb.243335","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T12:02:50Z","timestamp":1640088170000},"source":"Crossref","is-referenced-by-count":18,"title":["Severe hypoxia exposure inhibits larval brain development but does not affect the capacity to mount a cortisol stress response in zebrafish"],"prefix":"10.1242","volume":"225","author":[{"given":"Kristina V.","family":"Mikloska","sequence":"first","affiliation":[{"name":"Department of Integrative Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe A.","family":"Zrini","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-7063","authenticated-orcid":false,"given":"Nicholas J.","family":"Bernier","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,1,26]]},"reference":[{"key":"2022012610252800200_JEB243335C1","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.ygcen.2009.04.007","article-title":"Ontogeny of the corticotropin-releasing factor system in zebrafish","volume":"164","author":"Alderman","year":"2009","journal-title":"Gen. 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