Prior exposure to acute and chronic stressors potentiates the neuroinflammatory and microglial pro-inflammatory response to subsequent immune challenges suggesting that stressors sensitize or prime microglia. Stress-induced priming of the NLRP3 inflammasome has been implicated in this priming phenomenon, however the duration/persistence of these effects has not been investigated. In the present study, we examined whether exposure to a single acute stressor (inescapable tailshock) induced a protracted priming of the NLRP3 inflammasome as well as the neuroinflammatory, behavioral and microglial proinflammatory response to a subsequent immune challenge in hippocampus. In male Sprague-Dawley rats, acute stress potentiated the neuroinflammatory response (IL-1β, IL-6, and NFκBIα) to an immune challenge (lipopolysaccharide; LPS) administered 8 days after stressor exposure. Acute stress also potentiated the proinflammatory cytokine response (IL-1β, IL-6, TNF and NFκBIα) to LPS ex vivo. This stress-induced priming of microglia also was observed 28 days post-stress. Furthermore, challenge with LPS reduced juvenile social exploration, but not sucrose preference, in animals exposed to stress 8 days prior to immune challenge. Exposure to acute stress also increased basal mRNA levels of NLRP3 and potentiated LPS-induction of caspase-1 mRNA and protein activity 8 days after stress. The present findings suggest that acute stress produces a protracted vulnerability to the neuroinflammatory effects of subsequent immune challenges, thereby increasing risk for stress-related psychiatric disorders with an etiological inflammatory component. Further, these findings suggest the unique possibility that acute stress might induce innate immune memory in microglia.

中文翻译：

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急性应激诱导慢性神经炎症、小胶质细胞和行为启动：增强 NLRP3 炎症小体激活的作用

先前暴露于急性和慢性应激源会增强神经炎症和小胶质细胞对随后免疫挑战的促炎症反应，这表明应激源会使小胶质细胞敏感或启动。这种启动现象涉及应激诱导的 NLRP3 炎性体启动，但这些效应的持续时间/持续性尚未得到研究。在本研究中，我们检查了暴露于单一急性应激源（不可避免的尾震）是否会诱导 NLRP3 炎症小体的长期启动，以及对随后海马免疫挑战的神经炎症、行为和小胶质细胞促炎症反应。在雄性 Sprague-Dawley 大鼠中，急性应激增强了应激源暴露 8 天后对免疫攻击（脂多糖；LPS）的神经炎症反应（IL-1β、IL-6 和 NFκBIα）。急性应激还增强了体外对 LPS 的促炎细胞因子反应（IL-1β、IL-6、TNF 和 NFκBIα）。这种应激诱导的小胶质细胞启动也在应激后 28 天观察到。此外，在免疫攻击前 8 天暴露于压力的动物中，LPS 攻击减少了幼年的社会探索，但没有减少对蔗糖的偏好。应激后 8 天，暴露于急性应激也会增加 NLRP3 的基础 mRNA 水平，并增强 LPS 诱导的 caspase-1 mRNA 和蛋白活性。目前的研究结果表明，急性应激会对随后的免疫挑战的神经炎症效应产生长期的脆弱性，从而增加与应激相关的具有炎症病因的精神疾病的风险。此外，这些发现表明急性应激可能诱导小胶质细胞先天免疫记忆的独特可能性。