The Potential Role of the NLRP3 Inflammasome Activation as a Link Between Mitochondria ROS Generation and Neuroinflammation in Postoperative Cognitive Dysfunction

Frontiers in Cellular Neuroscience

Fan Yang¹  Penghui Wei²  Jianjun Li²  Qiang Zheng²  Wenxi Tang² 

[1] Department of Anesthesiology, Cheeloo College of Medicine, Shandong University, Jinan, China;Department of Anesthesiology, Qilu Hospital of Shandong University, Qingdao, China;

关键词: postoperative cognitive dysfunction;    NLRP3 inflammasome;    mitochondria-derived reactive oxygen species;    Interleukin-1β;    neuroinflammation;    microglia;   

DOI  :  10.3389/fncel.2019.00073

来源: DOAJ

【 摘 要 】

Postoperative cognitive dysfunction (POCD) is commonly observed in perioperative care following major surgery and general anesthesia in elderly individuals. No preventive or interventional agents have been established so far. Although the role of interleukin-1β (IL-1β)-mediated neuroinflammation following surgery and anesthesia is strongly implicated in POCD, the exact mechanism of action remains to be explored. Growing evidence has shown that mitochondria-derived reactive oxygen species (mtROS) are closely linked to IL-1β expression through a redox sensor known as the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Therefore, we hypothesize that the mechanisms underlying POCD involve the mtROS/NLRP3 inflammasome/IL-1β signaling pathway. Furthermore, we speculate that cholinergic anti-inflammatory pathway induced by α7 nicotinic acetylcholine receptor (a7nAChR) may be the potential upstream of mtROS/NLRP3 inflammasome/IL-1β signaling pathway in POCD. For validating the hypotheses, we provide experimental plan involving different paradigms namely; microglial cells and behavioral studies. The link between mtROS, the NLRP3 inflammasome, and IL-1β within and between these different stages in combination with mtROS and NLRP3 inflammasome agonists and inhibitors could be explored using techniques, such as knockout mice, small interference ribonucleic acid, flow cytometry, co-immunoprecipitation, and the Morris Water Maze test. We conclude that the NLRP3 inflammasome is a new preventive and therapeutic target for POCD.

【 授权许可】

Unknown