The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the cause of long-lasting depressive states is still unclear. To identify the effects of cumulative mild stress in brain development periods, we generated a young adult depression mouse model exposed to cumulative mild stress (CPMS; cumulative mild prenatal stress, mild maternal separation, and mild social defeat) to mimic early life adversities. CPMS mice exhibited more long-lasting anxiety and depression-like behaviors than groups exposed to single or double combinations of mild stress in young adult age. Using the molecular works, we found that inflammatory cytokines, especially interleukin (IL)-17, upregulated microglial activation in the hippocampus, amygdala, and prefrontal cortex of CPMS mice. In the brains of CPMS mice, we also identified changes in the T helper (Th)-17 cell population as well as differentiation. Finally, anti-IL-17 treatment rescued anxiety and depression-like behavior in CPMS mice. In conclusion, we found that cumulative mild stress promoted long-lasting depressive symptoms in CPMS mice through the upregulation of IL-17. We suggest that the CPMS model may be useful to study young adult depression and expect that IL-17 may be an important therapeutic target for depression in young adults.

中文翻译：

---

累积轻度压力诱导的白细胞介素17促进年轻成年小鼠的抑郁样行为

现代社会中，作为最常见的精神障碍之一，患有重度抑郁症的年轻成年患者的数量正在逐渐增加。早年的压力经历被认为是慢性抑郁症状以及晚年异常炎症反应的危险因素之一。尽管已发现抑郁症患者炎症活动增加，但长期抑郁状态的原因仍不清楚。为了确定累积轻度压力对大脑发育期的影响，我们生成了一个暴露于累积轻度压力（CPMS；累积轻度产前压力、轻度母体分离和轻度社会失败）的年轻成年抑郁症小鼠模型，以模拟早期生活中的逆境。与暴露于单一或双重轻度压力组合的青年组相比，CPMS 小鼠表现出更持久的焦虑和抑郁样行为。使用分子工作，我们发现炎性细胞因子，尤其是白细胞介素 (IL)-17，上调了 CPMS 小鼠海马、杏仁核和前额叶皮层中的小胶质细胞活化。在 CPMS 小鼠的大脑中，我们还发现了 T 辅助 (Th)-17 细胞群以及分化的变化。最后，抗 IL-17 治疗挽救了 CPMS 小鼠的焦虑和抑郁样行为。总之，我们发现累积的轻度压力通过上调 IL-17 促进了 CPMS 小鼠的长期抑郁症状。