Abstract
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.
Highlights
Major depressive disorder (MDD) is a chronic psychiatric disease characterized by a long-lasting state of depressive symptoms such as anxiety, loss of pleasure, and a feeling of low self-worth according to the World Mental Health Survey version of the Composite International Diagnostic Interview [1,2,3,4]
Cumulative mild stress led to depression‐like behavior in young adult mice C57BL/6N mice were exposed to mild prenatal stress (P), mild maternal separation (M), and mild social defeat stress (S) in the growth process (Additional file 1: Fig. S1)
Anti‐depressant treatment recovered anxiety and depression‐like behavior in CPMS mice It was confirmed that the anxiety and depression-like behaviors in CPMS mice were recovered with antidepressant venlafaxine treatment. 8-week-old mice, who started antidepressant administration from 7 weeks of a
Summary
Major depressive disorder (MDD) is a chronic psychiatric disease characterized by a long-lasting state of depressive symptoms such as anxiety, loss of pleasure, and a feeling of low self-worth according to the World Mental Health Survey version of the Composite International Diagnostic Interview [1,2,3,4]. Adult patients with depression exhibited higher IL-17 levels in serum than in healthy controls and have more Th17 cells, which produce IL-17 [14, 15]. Differentiation of Th17 cells from naïve CD4+ T helper cells requires the elevated expression of cytokines IL-6 or IL-21 which, in concert with transforming growth factor-beta (TGF-β), drive activation of signal transducer and activator of transcription 3 (STAT3) [18]. This transcription factor promotes the expression of RAR-related orphan receptor γt (RORγt) [19, 20]. TGF-β indirectly promotes the differentiation of Th17 cells by preventing Th1 and Th2 cell differentiation [21,22,23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
