Post-traumatic stress disorder (PTSD) is a psychiatric illness that results in an increased risk for a variety of inflammatory diseases. The exact etiology of this increased risk is unknown, and thus several animal models have been developed to investigate the neuroimmune interactions of PTSD. Repeated social defeat stress (RSDS) is an established preclinical model of psychological trauma that recapitulates certain behavioral and inflammatory aspects of human PTSD. Furthermore, RSDS has been utilized to subgroup animals into susceptible and resilient populations based on one specific behavioral phenotype (i.e., social interaction). Herein, we conducted an extensive investigation of circulating inflammatory proteins after RSDS and found significant elevations in various cytokines and chemokines after exposure to RSDS. When categorizing animals into either susceptible or resilient populations based on social interaction, we found no inflammatory or other behavioral differences between these subgroups. Furthermore, correlative analyses found no significant correlation between social interaction parameters and inflammation. In contrast, parameters from the elevated zero maze (EZM) demonstrated significant associations and clustering to five circulating cytokines. When animals were subdivided into susceptible and resilient populations solely based upon combined EZM performance, significant inflammatory differences were evident between these groups. Strikingly, these circulating inflammatory proteins displayed a stronger predictive ability of EZM performance compared to social interaction test performance. These findings provide new insights into inflammatory markers associated with RSDS, and the utility of EZM to effectively group RSDS-exposed mice into populations with differential levels of peripheral inflammation.

中文翻译：

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周围炎症与反复社交失败压力下零迷宫行为的升高密切相关


创伤后应激障碍 (PTSD) 是一种精神疾病，会导致多种炎症性疾病的风险增加。这种风险增加的确切病因尚不清楚，因此已经开发了几种动物模型来研究 PTSD 的神经免疫相互作用。重复社交失败压力（RSDS）是一种已建立的心理创伤临床前模型，它概括了人类创伤后应激障碍（PTSD）的某些行为和炎症方面。此外，RSDS 已被用来根据一种特定的行为表型（即社会互动）将动物分为易感群体和弹性群体。在此，我们对 RSDS 后的循环炎症蛋白进行了广泛的研究，发现暴露于 RSDS 后各种细胞因子和趋化因子显着升高。当根据社会互动将动物分为易感群体或弹性群体时，我们发现这些亚组之间没有炎症或其他行为差异。此外，相关分析发现社交互动参数与炎症之间没有显着相关性。相比之下，高架零迷宫 (EZM) 的参数显示出与五种循环细胞因子的显着关联和聚类。当仅根据综合 EZM 表现将动物细分为易感群体和弹性群体时，这些群体之间明显存在明显的炎症差异。引人注目的是，与社交互动测试表现相比，这些循环炎症蛋白对 EZM 表现表现出更强的预测能力。 这些发现为与 RSDS 相关的炎症标志物以及 EZM 有效地将暴露于 RSDS 的小鼠分组为具有不同外周炎症水平的群体的效用提供了新的见解。