Background::Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS’s response to SD.Methods::Middle-aged wild-type (WT) C57BL/6 and CX3CR1 -/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. Results::CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1 -/- S group, the CX3CR1 -/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. Conclusions::These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

Sleep deprivation;Cognitive dysfunction;Microglia;CX3CR1 deficiency

Xin Jiawei;Wang Chao;Cheng Xiaojuan;Xie Changfu;Zhang Qiuyang;Ke Yilang;Huang Xuanyu;Chen Xiaochun;Pan Xiaodong

Department of Neurology, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China;Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China;Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Medical University, Fuzhou, Fujian 350001, China;School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian 350001, China;Department of Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China;Fujian Key Laboratory of Vascular Aging, Fujian Medical University, Fuzhou, Fujian 350001, China

中华医学杂志（英文版）

[1]Xin Jiawei;Wang Chao;Cheng Xiaojuan;Xie Changfu;Zhang Qiuyang;Ke Yilang;Huang Xuanyu;Chen Xiaochun;Pan Xiaodong-.CX3C-chemokine receptor 1 modulates cognitive dysfunction induced by sleep deprivation)[J].中华医学杂志（英文版）,2022(02):205-215

CX3CR1

chemokine,receptor,modulates,cognitive,dysfunction,induced,by,sleep,deprivation,Background,Microglia,plays,indispensable,role,pathological,process,Here,potential,microglial,modulating,cognition,decline,during,was,evaluated,terms,neuroinflammation,synaptic,pruning,In,this,study,aimed,investigat,whether,interference,knockout,affects,CNS,Methods,Middle,aged,wild,type,WT,C57BL,mice,were,either,subjected,allowed,normal,mimic,pathophysiological,changes,middle,people,after,staying,night,After,which,behavioral,histological,tests,used,explore,their,different,Results,deficiency,prevented,impairments,unlike,groups,Compared,reported,markedly,decreased,cellular,oncogene,fos,density,dentate,gyrus,DG,expression,inflammatory,cytokines,phagocytosis,related,factors,whereas,increased,levels,anti,hippocampus,significant,spines,also,noted,Conclusions,These,findings,suggest,that,leads,cerebral,behaviors,responses,attenuating,activity,modification,possible,mechanism,candidates,indicate,therapeutic,target,prevention,loss,Sleep,Cognitive

0.565226