Ibrutinib alleviated LPS-induced neuroinflam⁃mation and synaptic defects in mouse model of depression  

作　　者：LI Wei-fen Tahir Ali HE Kai-wu LIU Zi-zhen Fawad Ali Shah REN Qing-guo LIU Yan JIANG An-long LI Shu-peng 

机构地区：[1]Laboratory of Chemical Genomics,School of Chemical Biology and Biotechnology,Peking Uni-versity Shenzhen Graduate School,Shenzhen 518055,China

出　　处：《中国药理学与毒理学杂志》2021年第9期684-685,共2页Chinese Journal of Pharmacology and Toxicology

摘　　要：OBJECTIVE Previous studies have demonstrated a close association between an altered immune system and major depressive disorders,and inhibition of neuroinflammation may represent an alternative mechanism to treat depression.Recently,the anti-inflammatory activ⁃ity of ibrutinib has been reported.However,the effect of ibrutinib on neuroinflammation-induced depression and its underlying mechanism has not been comprehensively studied.Therefore,we aimed to elucidate the potential anti-depres⁃sive role and mechanism of ibrutinib against neu⁃roinflammation-induced depression and synaptic defects.METHODS AND RESULTS Ibrutinib treatment significantly reduced lipopolysaccha⁃ride(LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-κB acti⁃vation,decreasing proinflammatory cytokine levels,and normalizing redox signaling and its downstream components,including Nrf2,HO-1,and SOD2,as well as glial cell activation mark⁃ers,such as Iba-1 and GFAP.Further,ibrutinib treatment inhibited LPS-activated inflammasome activation by targeting NLRP3/P38/caspase-1 signaling.Interestingly,LPS reduced the number of dendritic spines and expression of BDNF,and synaptic-related markers,including PSD95,snap25,and synaptophysin,were improved by ibrutinib treatment in the hippocampal area of the mouse brain.CONCLUSION Ibrutinib can allevi⁃ate neuroinflammation and synaptic defects,sug⁃gesting it has antidepressant potential against LPS-induced neuroinflammation and depression.

关 键 词：ibrutinib NEUROINFLAMMATION depres⁃sion synaptic defects 

分 类 号：R965[医药卫生—药理学]