Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Division of Biosciences, The Ohio State University College of Dentistry, Columbus, OH, USA.
Nat Immunol. 2022 Nov;23(11):1527-1535. doi: 10.1038/s41590-022-01321-z. Epub 2022 Nov 11.
Myriad clinical findings provide links between chronic stressors, inflammation, and mood disorders. Furthermore, traumatic or chronic exposure to psychological stressors may promote stress sensitization, in which individuals have long-term complications, including increased vulnerability to subsequent stressors. Post-traumatic stress disorder (PTSD) is a clinically relevant example of stress sensitization. PTSD alters neuronal circuitry and mood; however, the mechanisms underlying long-term stress sensitization within this disorder are unclear. Rodent models of chronic social defeat recapitulate several key physiological, immunological, and behavioral responses associated with psychological stress in humans. Repeated social defeat (RSD) uniquely promotes the convergence of neuronal, central inflammatory (microglial), and peripheral immune (monocyte) pathways, leading to prolonged anxiety, social withdrawal, and cognitive impairment. Moreover, RSD promotes stress sensitization, in which mice are highly sensitive to subthreshold stress exposure and recurrence of anxiety weeks after the cessation of stress. Therefore, the purpose of this Review is to discuss the influence of social-defeat stress on the immune system that may underlie stress sensitization within three key cellular compartments: neurons, microglia, and monocytes. Delineating the mechanisms of stress sensitization is critical in understanding and treating conditions such as PTSD.
多种临床发现将慢性应激源、炎症和情绪障碍联系起来。此外，创伤或慢性暴露于心理应激源可能会促进应激敏感化，个体出现长期并发症，包括对随后的应激源的易感性增加。创伤后应激障碍（PTSD）是应激敏感化的一个临床相关例子。PTSD 改变了神经元回路和情绪；然而，该疾病中导致长期应激敏感化的机制尚不清楚。慢性社会挫败的啮齿动物模型再现了与人类心理应激相关的几种关键生理、免疫和行为反应。反复社会挫败（RSD）独特地促进了神经元、中枢炎症（小胶质细胞）和外周免疫（单核细胞）途径的收敛，导致持续的焦虑、社交回避和认知障碍。此外，RSD 促进了应激敏感化，即在应激停止数周后，小鼠对阈下应激暴露和焦虑复发高度敏感。因此，本综述的目的是讨论社会挫败应激对免疫系统的影响，这可能是应激敏感化在三个关键细胞区室中的基础：神经元、小胶质细胞和单核细胞。阐明应激敏感化的机制对于理解和治疗 PTSD 等疾病至关重要。
