东南大学：睡不好容易痴呆，和肠菌失调有关？

Brain Behavior and Immunity[IF:19.227]

① 慢性睡眠剥夺（SD）诱导小鼠存在肠菌失调，激活肠道和大脑的NLRP3炎性小体，会破坏肠道/血脑屏障，损害认知功能；

② 移植“SD菌群”几乎可以模拟所有慢性睡眠剥夺引起的病理和行为变化；

③ 敲除小鼠NLRP3基因，SD剥夺引起的行为和病理异常均可得到改善，下调海马区NLRP3可抑制神经炎症，改善SD引起的突触损伤和认知障碍；

④ 在慢性SD小鼠中，下调肠道中NLRP3表达可保护肠道屏障，降低血液炎性因子水平，下调大脑中NLRP3表达，改善认知功能。

Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation
11-24, doi: 10.1016/j.bbi.2022.11.013

【主编评语】良好的睡眠有利于人体保持最佳的认知功能，包括决策、注意力、学习和各种类型的记忆。大量的动物和临床研究发现睡眠障碍会导致认知障碍，并可能增加患阿尔茨海默病的风险。近日，东南大学附属中大医院任庆国及团队在Brain Behavior and Immunity上发表最新研究，通过动物实验发现，慢性睡眠剥夺引起的肠道菌群失调通过肠道、脑部NLRP3炎症小体激活，进一步导致认知障碍的潜在机理，为未来通过靶向肠道菌群干预潜在的痴呆奠定了新基础。

Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation

慢性睡眠剥夺时，肠道失调通过肠道和大脑NLRP3炎症小体激活介导认知障碍

10.1016/j.bbi.2022.11.013

11-24, Article

Abstract:
Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood–brain barrier, and impaired cognitive function in mice. Transplantation of “SD microbiota” could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that downregulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.

First Authors:
Na Zhao,Qiu-Gu Chen,Xiu Chen

Correspondence Authors:
Qing-Guo Ren

All Authors:
Na Zhao,Qiu-Gu Chen,Xiu Chen,Xue-Ting Liu,Fan Geng,Meng-Meng Zhu,Fu-Ling Yan,Zhi-Jun Zhang,Qing-Guo Ren