Sleep deprivation is a form of stress that provokes both inflammatory responses and neuropsychiatric disorders. Because persistent inflammation is implicated as a physiological process in anxiety disorders, we investigated the contributions of NLRP3 inflammasome signaling to anxiety and anxiolytic properties of flavanol diets in a model of chronic sleep deprivation. The results show a flavanol-rich dietary preparation (FDP) exhibits anxiolytic properties by attenuating markers of neuroimmune activation, which included IL-1β upregulation, NLRP3 signaling, and microglia activation in the cortex and hippocampus of sleep-deprived mice. Production of IL-1β and NLRP3 were critical for both anxiety phenotypes and microglia activation. Individual FDP metabolites potently inhibited IL-1β production from microglia following stimulation with NLRP3-specific agonists, supporting anxiolytic properties of FDP observed in models of sleep deprivation involve inhibition of the NLRP3 inflammasome. The study further showed sleep deprivation alters the expression of the circadian gene Bmal1, which critically regulated NLRP3 expression and IL-1β production.

睡眠剥夺是一种压力形式，会引发炎症反应和神经精神疾病。因为持续性炎症与焦虑症的生理过程有关，我们在慢性睡眠剥夺模型中研究了 NLRP3 炎性体信号传导对黄烷醇饮食的焦虑和抗焦虑特性的贡献。结果表明，富含黄烷醇的膳食制剂 (FDP) 通过减弱神经免疫激活标志物（包括 IL-1β 上调、NLRP3 信号传导和睡眠剥夺小鼠皮质和海马中的小胶质细胞活化）表现出抗焦虑特性。IL-1β 和 NLRP3 的产生对于焦虑表型和小胶质细胞激活都至关重要。在用 NLRP3 特异性激动剂刺激后，单个 FDP 代谢物有效抑制小胶质细胞产生 IL-1β，支持在睡眠剥夺模型中观察到的 FDP 的抗焦虑特性涉及抑制 NLRP3 炎性体。该研究进一步表明，睡眠不足会改变昼夜节律基因的表达Bmal1，它严格调节 NLRP3 表达和 IL-1β 产生。