Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain

作者：Zhuang Peng, Sha Peng, Kangguang Lin, Bin Zhao, Lai Wei, Qinhui Tuo, Duan‐Fang Liao, Tifei Yuan, Zhe Shi · 发表于：Journal of Neuroinflammation · 年份：2022 · DOI：10.1186/s12974-022-02543-6 · 被引用次数：88 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol、Neuroinflammation and Neurodegeneration Mechanisms

Abstract Background Depression is a recurrent and devastating mental disease that is highly prevalent worldwide. Prolonged exposure to stressful events or a stressful environment is detrimental to mental health. In recent years, an inflammatory hypothesis has been implicated in the pathogenesis of stress-induced depression. However, less attention has been given to the initial phases, when a series of stress reactions and immune responses are initiated. Peripheral CD4 + T cells have been reported as the major contributors to the occurrence of mental disorders. Chronic stress exposure-evoked release of cytokines can promote the differentiation of peripheral CD4 + cells into various phenotypes. Among them, Th17 cells have attracted much attention due to their high pathogenic potential in central nervous system (CNS) diseases. Thus, we intended to determine the crucial role of CD4 + Th17 cells in the development of specific subtypes of depression and unravel the underpinnings of their pathogenetic effect. Methods In the present research, a daily 6-h restraint stress paradigm was employed in rats for 28 successive days to mimic the repeated mild and predictable, but inevitable environmental stress in our daily lives. Then, depressive-like symptoms, brain–blood barrier (BBB) permeability, neuroinflammation, and the differentiation and functional changes of CD4 + cells were investigated. Results We noticed that restrained rats showed significant depressive-like symptoms, concomitan...