{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:36:19Z","timestamp":1782484579804,"version":"3.54.5"},"reference-count":302,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South Ural State Universit","award":["FENU-2023-0014"],"award-info":[{"award-number":["FENU-2023-0014"]}]},{"name":"South Ural State Universit","award":["25-13-20056"],"award-info":[{"award-number":["25-13-20056"]}]},{"name":"the RSF","award":["FENU-2023-0014"],"award-info":[{"award-number":["FENU-2023-0014"]}]},{"name":"the RSF","award":["25-13-20056"],"award-info":[{"award-number":["25-13-20056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript critically examines the spectrum of experimental strategies used to model PTSD in zebrafish, with a focus on the comparative efficacy and validity of acute, chronic, and complex stress paradigms. Among these, 14\u201315-day chronic unpredictable stress (CUS\/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes\u2014such as anxiety-like behavior, cortisol dysregulation, and neuroinflammatory gene activation. We discuss the influence of environmental, developmental, and genetic factors on stress responses, and highlight the importance of standardized behavioral and molecular endpoints for model validation. While alternative paradigms\u2014including acute, social, pharmacological, and predator-based models\u2014offer mechanistic insights, their translational relevance remains limited without further refinement. We conclude by outlining future directions for zebrafish-based PTSD research, emphasizing the need for protocol harmonization, integration of multi-modal readouts, and exploration of individual variability to enhance the translational value of this model system.<\/jats:p>","DOI":"10.3390\/biology14080939","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T12:56:43Z","timestamp":1753448203000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Zebrafish as a Model Organism for Post-Traumatic Stress Disorder: Insights into Stress Mechanisms and Behavioral Assays"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3101-9655","authenticated-orcid":false,"given":"Alexey","family":"Sarapultsev","sequence":"first","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia"},{"name":"Russian\u2013Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-8358","authenticated-orcid":false,"given":"Maria","family":"Komelkova","sequence":"additional","affiliation":[{"name":"Russian\u2013Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9544-1885","authenticated-orcid":false,"given":"Oleg","family":"Lookin","sequence":"additional","affiliation":[{"name":"National Scientific Medical Center, Astana 010009, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-6680","authenticated-orcid":false,"given":"Sergey","family":"Khatsko","sequence":"additional","affiliation":[{"name":"Anatomical and Physiological Experimental Laboratory, Department of Experimental Biology and Biotechnology, Institute of Natural Sciences and Mathematics, 48 Kuybysheva Str., 620026 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-8976","authenticated-orcid":false,"given":"Alexander","family":"Zhdanov","sequence":"additional","affiliation":[{"name":"Anatomical and Physiological Experimental Laboratory, Department of Experimental Biology and Biotechnology, Institute of Natural Sciences and Mathematics, 48 Kuybysheva Str., 620026 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislav","family":"Fedorov","sequence":"additional","affiliation":[{"name":"Russian\u2013Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-2376","authenticated-orcid":false,"given":"Evgenii","family":"Gusev","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6745-6035","authenticated-orcid":false,"given":"Alexander","family":"Trofimov","sequence":"additional","affiliation":[{"name":"Biology Department, School of Sciences and Humanities, Nazarbayev University, 53 Kabanbai Batyr Ave., Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2219-3301","authenticated-orcid":false,"given":"Tursonjan","family":"Tokay","sequence":"additional","affiliation":[{"name":"Biology Department, School of Sciences and Humanities, Nazarbayev University, 53 Kabanbai Batyr Ave., Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Hubei Key Laboratory of Biological Targeted Therapy, China-Russia Medical Research Center for Stress Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.tips.2013.12.002","article-title":"Zebrafish as an emerging model for studying complex brain disorders","volume":"35","author":"Kalueff","year":"2014","journal-title":"Trends Pharmacol. 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