Anxiolytic effects of NLRP3 inflammasome inhibition in a model of chronic sleep deprivation.

Anxiolytic effects of NLRP3 inflammasome inhibition in a model of chronic sleep deprivation.
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NLRP 3炎性小体抑制在慢性睡眠剥夺模型中的溶瘤作用。

DOI:
10.1038/s41398-020-01189-3
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发表时间:
2021-01-14
影响因子:
6.8
通讯作者:
Pasinetti GM
Pasinetti GM
中科院分区:
医学1区
文献类型:
--
作者:
Smith C;Trageser KJ;Wu H;Herman FJ;Iqbal UH;Sebastian-Valverde M;Frolinger T;Zeng E;Pasinetti GM

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睡眠不足是一种压力,既会引发炎症反应,也会引发神经精神障碍。由于持续性炎症是焦虑症的一个生理过程,我们在一个慢性睡眠剥夺模型中研究了NLRP3炎症体信号对黄烷醇饮食的焦虑和抗焦虑特性的贡献。结果表明,富含黄烷醇的饮食制剂通过减弱神经免疫激活的标志,包括IL-1β上调,NLRP3信号,以及睡眠剥夺小鼠皮质和海马区小胶质细胞的激活,显示出抗焦虑的特性。IL-1β和NLRP3的产生对焦虑表型和小胶质细胞激活都是至关重要的。在被NLRP3特异性激动剂刺激后,个别FDP代谢产物有效地抑制小胶质细胞IL-1β的产生,支持在睡眠剥夺模型中观察到的FDP的抗焦虑特性包括抑制NLRP3炎症体。这项研究进一步表明,睡眠剥夺改变了生物钟基因BMal1的表达,该基因对NLRP3的表达和IL-1β的产生起着至关重要的调节作用。
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.
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