Aging is associated with an enhanced neuroinflammatory response to acute immune challenge, often termed "inflammaging." However, there are conflicting reports about whether baseline levels of inflammatory markers are elevated under ambient conditions in the aging brain, or whether such changes are observed predominantly in response to acute challenge. The present studies utilized two distinct approaches to assess inflammatory markers in young and aging Fischer 344 rats. Experiment 1 examined total tissue content of inflammatory markers from hippocampus of adult (3 month), middle-aged (12 month), and aging (18 month) male Fischer (F) 344 rats using multiplex analysis (23-plex). Though trends emerged for several cytokines, no significant differences in basal tissue content were observed across the 3 ages examined. Experiment 2 measured extracellular concentrations of inflammatory factors in the hippocampus from adult (3 month) and aging (18 month) males and females using large-molecule in vivo microdialysis. Although few significant aging-related changes were observed, robust sex differences were observed in extracellular concentrations of CCL3, CCL20, and IL-1α. Experiment 2 also evaluated the involvement of the P2X7 purinergic receptor in neuroinflammation using reverse dialysis of the selective agonist BzATP. BzATP produced an increase in IL-1α and IL-1β release and rapidly suppressed the release of CXCL1, CCL2, CCL3, CCL20, and IL-6. Other noteworthy sex by aging trends were observed in CCL3, IL-1β, and IL-6. Together, these findings provide important new insight into late-aging and sex differences in neuroinflammation, and their regulation by the P2X7 receptor.

中文翻译：

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使用大分子微透析评估衰老海马中的神经炎症：性别差异和嘌呤能受体的作用

衰老与对急性免疫挑战的神经炎症反应增强有关，通常称为“炎症”。然而，关于在环境条件下老化大脑中炎症标志物的基线水平是否升高，或者这种变化是否主要在应对急性挑战时观察到，存在相互矛盾的报道。本研究使用两种不同的方法来评估年轻和衰老 Fischer 344 大鼠的炎症标志物。实验 1 使用多重分析 (23-plex) 检查了成年 (3 个月)、中年 (12 个月) 和衰老 (18 个月) 雄性 Fischer (F) 344 大鼠海马中炎症标志物的总组织含量。尽管出现了几种细胞因子的趋势，但在所检查的 3 个年龄组中未观察到基础组织含量的显着差异。实验 2 使用大分子体内微透析测量了成年（3 个月）和衰老（18 个月）男性和女性海马中炎症因子的细胞外浓度。尽管几乎没有观察到与衰老相关的显着变化，但在 CCL3、CCL20 和 IL-1α 的细胞外浓度中观察到了强烈的性别差异。实验 2 还使用选择性激动剂 BzATP 的反向透析评估了 P2X7 嘌呤能受体在神经炎症中的作用。BzATP 增加了 IL-1α 和 IL-1β 的释放，并迅速抑制了 CXCL1、CCL2、CCL3、CCL20 和 IL-6 的释放。在 CCL3、IL-1β 和 IL-6 中观察到其他值得注意的性别老化趋势。总之，这些发现为神经炎症的晚期衰老和性别差异提供了重要的新见解，