Sarapultsev Alexey, Komelkova Maria, Lookin Oleg, Khatsko Sergey, Zhdanov Alexander, Fedorov Stanislav, Gusev Evgenii, Trofimov Alexander, Tokay Tursonjan, Hu Desheng
Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia.
Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, 454080 Chelyabinsk, Russia.
Biology (Basel). 2025 Jul 25;14(8):939. doi: 10.3390/biology14080939.
The zebrafish () 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, 14-15-day chronic unpredictable stress (CUS/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes-such 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-including acute, social, pharmacological, and predator-based models-offer 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.
斑马鱼已成为研究创伤后应激障碍（PTSD）机制的强大模式生物，在转化相关性、遗传可追踪性和成本效益方面具有独特优势。作为我们最近系统综述的逻辑延续，本手稿批判性地审视了用于斑马鱼PTSD建模的实验策略范围，重点关注急性、慢性和复杂应激范式的比较效果和有效性。其中，14 - 15天的慢性不可预测应激（CUS/UCS）方案被确定为金标准，可可靠地诱导核心PTSD样表型，如焦虑样行为、皮质醇失调和神经炎症基因激活。我们讨论了环境、发育和遗传因素对应激反应的影响，并强调标准化行为和分子终点对模型验证的重要性。虽然包括急性、社会、药理学和基于捕食者的模型在内的替代范式提供了机制见解，但未经进一步完善，它们的转化相关性仍然有限。我们通过概述基于斑马鱼的PTSD研究的未来方向来得出结论，强调需要协议协调、多模态读数整合以及探索个体变异性，以提高该模型系统的转化价值。
