Dutcher Ethan G, Pama E A Claudia, Lynall Mary-Ellen, Khan Shahid, Clatworthy Menna R, Robbins Trevor W, Bullmore Edward T, Dalley Jeffrey W
Department of Psychology, University of Cambridge, Cambridge, UK.
Department of Psychiatry, University of Cambridge, Cambridge, UK.
Brain Neurosci Adv. 2020 Dec 28;4:2398212820978049. doi: 10.1177/2398212820978049. eCollection 2020 Jan-Dec.
Repeated maternal separation is the most widely used pre-clinical approach to investigate the relationship between early-life chronic stress and its neuropsychiatric and physical consequences. In this systematic review, we identified 46 studies that conducted repeated maternal separation or single-episode maternal separation and reported measurements of interleukin-1b, interleukin-6, interleukin-10, tumour necrosis factor-alpha, or microglia activation and density. We report that in the short-term and in the context of later-life stress, repeated maternal separation has pro-inflammatory immune consequences in diverse tissues. Repeated maternal separation animals exhibit greater microglial activation and elevated pro-inflammatory cytokine signalling in key brain regions implicated in human psychiatric disorders. Notably, repeated maternal separation generally has no long-term effect on cytokine expression in any tissue in the absence of later-life stress. These observations suggest that the elevated inflammatory signalling that has been reported in humans with a history of early-life stress may be the joint consequence of ongoing stressor exposure together with potentiated neural and/or immune responsiveness to stressors. Finally, our findings provide detailed guidance for future studies interrogating the causal roles of early-life stress and inflammation in disorders such as major depression.
反复母婴分离是临床前研究中最广泛使用的方法，用于探究早期慢性应激与其神经精神和身体后果之间的关系。在这项系统评价中，我们识别出46项进行了反复母婴分离或单次母婴分离并报告了白细胞介素-1β、白细胞介素-6、白细胞介素-10、肿瘤坏死因子-α或小胶质细胞活化及密度测量值的研究。我们报告称，在短期以及在后期生活应激的背景下，反复母婴分离在多种组织中具有促炎免疫后果。反复母婴分离的动物在涉及人类精神疾病的关键脑区表现出更大的小胶质细胞活化和升高的促炎细胞因子信号传导。值得注意的是，在没有后期生活应激的情况下，反复母婴分离通常对任何组织中的细胞因子表达没有长期影响。这些观察结果表明，有早期生活应激史的人类中所报告的炎症信号升高可能是持续暴露于应激源以及对应激源增强的神经和/或免疫反应共同作用的结果。最后，我们的研究结果为未来研究探究早期生活应激和炎症在诸如重度抑郁症等疾病中的因果作用提供了详细指导。
