Abstract

Stress is a common cause of neuropsychiatric disorders, evoking multiple behavioral, endocrine and neuro-immune deficits. Animal models have been extensively used to understand the mechanisms of stress-related disorders and to develop novel strategies for their treatment. Complementing rodent and clinical studies, the zebrafish (Danio rerio) is one of the most important model organisms in biomedicine. Rapidly becoming a popular model species in stress neuroscience research, zebrafish are highly sensitive to both acute and chronic stress, and show robust, well-defined behavioral and physiological stress responses. Here, we critically evaluate the utility of zebrafish-based models for studying acute and chronic stress-related CNS pathogenesis, assess the advantages and limitations of these aquatic models, and emphasize their relevance for the development of novel anti-stress therapies. Overall, the zebrafish emerges as a powerful and sensitive model organism for stress research. Although these fish generally display evolutionarily conserved behavioral and physiological responses to stress, zebrafish-specific aspects of neurogenesis, neuroprotection and neuro-immune responses may be particularly interesting to explore further, as they may offer additional insights into stress pathogenesis that complement (rather than merely replicate) rodent findings. Compared to mammals, zebrafish models are also characterized by increased availability of gene-editing tools and higher throughput of drug screening, thus being able to uniquely empower translational research of genetic determinants of stress and resilience, as well as to foster innovative CNS drug discovery and the development of novel anti-stress therapies.

摘要

压力是神经精神疾病的常见原因，引起多种行为，内分泌和神经免疫缺陷。动物模型已被广泛用于理解与压力有关的疾病的机制，并开发出新颖的治疗策略。作为啮齿动物和临床研究的补充，斑马鱼（Danio rerio）是生物医学中最重要的模型生物之一。斑马鱼迅速成为应激神经科学研究中的流行模型物种，对急性和慢性应激高度敏感，并表现出强大的，明确的行为和生理应激反应。在这里，我们批判性地评估基于斑马鱼的模型在研究急性和慢性应激相关中枢神经系统发病机制中的效用，评估这些水生模型的优势和局限性，并强调它们与新型抗应激疗法的相关性。总体而言，斑马鱼作为压力研究的强大而敏感的模型生物而出现。尽管这些鱼通常表现出对压力的进化保守的行为和生理反应，但斑马鱼特定的神经发生方面，进一步探索神经保护和神经免疫应答可能特别有趣，因为它们可能提供补充（而非仅仅复制）啮齿动物发现的应激发病机制的其他见解。与哺乳动物相比，斑马鱼模型还具有以下特点：基因编辑工具的可用性提高和药物筛选的通量更高，因此能够独特地促进对压力和适应力的遗传决定因素进行转化研究，并促进创新的中枢神经系统药物发现和新型抗应激疗法的发展。