Maj Institute of Pharmacology Polish Academy of Sciences, Smetna Street 12, 31-343 Kraków, Poland.
Cells. 2021 Jun 29;10(7):1630. doi: 10.3390/cells10071630.
Long-lasting stress factors, both biological and psychological, are commonly accepted as the main cause of depressive disorders. Several animal models, using various stressful stimuli, have been used to find biochemical and molecular alterations that could help us understand the etiopathogenesis of depression. However, recent sophisticated studies indicate that the most frequently used animal models of stress only capture a portion of the molecular features associated with complex human disorders. On the other hand, some of these models generate groups of animals resilient to stress. Studies of the mechanisms of stress resilience bring us closer to understanding the process of adapting to aversive stimuli and the differences between stress-susceptible vs. resilient phenotypes. Especially interesting in this context is the chronic mild stress (CMS) experimental paradigm, most often using rats. Studies using this animal model have revealed that biochemical (e.g., the dopamine D2 receptor) and molecular (e.g., microRNA) alterations are dynamic (i.e., depend on stress duration, 2 vs. 7 weeks) and much more pronounced in stress-resilient than stress-susceptible groups of animals. We strongly suggest that studies aimed at understanding the molecular and biochemical mechanisms of depression must consider these dynamics. A good candidate to serve as a biomarker in such studies might be serum microRNA, since it can be obtained relatively easily from living individuals at various time points.
长期的生物和心理应激因素被普遍认为是抑郁障碍的主要原因。为了帮助我们理解抑郁的病因和发病机制，已经使用了多种使用不同应激刺激的动物模型来寻找可能存在的生化和分子改变。然而，最近的精细研究表明，最常使用的应激动物模型仅能捕捉到与复杂人类疾病相关的部分分子特征。另一方面，这些模型中的一些会产生对压力有抵抗力的动物群体。应激弹性机制的研究使我们更深入地了解适应厌恶刺激的过程以及应激敏感与应激弹性表型之间的差异。在这方面特别有趣的是慢性轻度应激（CMS）实验范式，最常用于大鼠。使用这种动物模型的研究表明，生化（例如多巴胺 D2 受体）和分子（例如 microRNA）改变是动态的（即，取决于应激持续时间，2 周与 7 周），在应激弹性动物群体中比应激敏感动物群体更为明显。我们强烈建议，旨在理解抑郁的分子和生化机制的研究必须考虑到这些动态。血清 microRNA 可能是此类研究中的一个很好的候选生物标志物，因为它可以相对容易地从不同时间点的活体个体中获得。
