School of Life Sciences and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Behav Brain Res. 2021 Sep 24;414:113486. doi: 10.1016/j.bbr.2021.113486. Epub 2021 Jul 22.
Depression is a common psychiatric disorder that can occur throughout an individual's lifespan. Chronic unpredictable mild stress (CUMS) protocol is currently the most commonly used to develop an animal model of depression. Due to the variable duration and procedure of CUMS, it is difficult to reproduce and explore the mechanism of CUMS-induced depression effectively. In the present study, the CUMS-induced behavioral phenotypes were assessed in male C57BL/6J mice at the age of 9-18 weeks. The mice stressed for 3-8 weeks exhibited lower body weight as well as longer immobility time of forced swim and tail suspension test compared to control mice. Moreover, lessening and impairment of hippocampal neurons was found in stressed mice at the age of 18 weeks, which was correlated with increased relative mRNA expression levels of inflammatory cytokines BDNF, Htr1a, and IL-6 in the hippocampus. Nevertheless, no difference between stressed and control mice was observed neither in the sucrose preference nor in the open field test (except for vertical activity in OFT) at the age of 18 weeks. These findings reveal that 3-8 weeks of chronic stress could induce depression-like alterations in male C57BL/6J mice and the behavioral adaptation of aged mice might fail to the availability of the depression model.
抑郁症是一种常见的精神障碍，可以发生在个体的整个生命周期中。慢性不可预测轻度应激（CUMS）方案目前是最常用于开发抑郁症动物模型的方法。由于 CUMS 的持续时间和程序不同，因此很难有效地再现和探索 CUMS 诱导的抑郁症的机制。在本研究中，在 9-18 周龄的雄性 C57BL/6J 小鼠中评估了 CUMS 诱导的行为表型。与对照小鼠相比，应激 3-8 周的小鼠体重较低，强迫游泳和悬尾试验的不动时间较长。此外，在 18 周龄的应激小鼠中发现海马神经元减少和损伤，这与海马中炎症细胞因子 BDNF、Htr1a 和 IL-6 的相对 mRNA 表达水平升高有关。然而，在 18 周龄时，应激和对照小鼠在蔗糖偏好或旷场试验（除 OFT 中的垂直活动外）中均未观察到差异。这些发现表明，3-8 周的慢性应激可诱导雄性 C57BL/6J 小鼠出现类似抑郁症的改变，而老年小鼠的行为适应可能无法适应抑郁症模型的出现。
