title: Involvement of inflammasome activation in lipopolysaccharide-induced mice depressive-like behaviors.
abstract: OBJECTIVE
  The NLRP3 inflammasome is a cytoplasmic multiprotein complex of the innate immune system that regulates the cleavage of interleukin-1β and interleukin-18 precursors. It can detect a wide range of danger signals and trigger a series of immune-inflammatory reactions. There were plenty of studies indicating that activation of the immune system played pivotal roles in depression. However, the underlying mechanisms of immune-depression interactions remained elusive and there was no report about the involvement of inflammasome activation in depression.
  
  
  METHODS
  We established an acute depression mouse model with lipopolysaccharide to explore the involvement of inflammasome activation in depression.
  
  
  RESULTS
  The lipopolysaccharide-treated mice displayed depressive-like behaviors and pro-inflammatory cytokine interleukin-1β protein and mRNA levels significantly increased. The NLRP3 inflammasome mRNA expression level also significantly elevated in depressed mice brain. Pretreatment with the NLRP3 inflammasome inhibitor Ac-YVAD-CMK significantly abrogated the depressive-like behaviors induced by lipopolysaccharide.
  
  
  CONCLUSIONS
  These data suggest for the first time that the NLRP3 inflammasome is involved in lipopolysaccharide-induced mice depressive-like behaviors. The NLRP3 inflammasome may be a central mediator between immune activation and depression, which raises the possibility that it may be a more specific target for the depression treatments in the near future.
authors.affiliation: Laboratory of Stress Medicine, Faculty of Psychology and Mental Health, Second Military Medical University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Yun-Li
authors.initials: YL
authors.lastname: Peng
authors.forename: Yun-Zi
authors.initials: YZ
authors.lastname: Liu
authors.forename: Teng-Yun
authors.initials: TY
authors.lastname: Wu
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Shen
authors.forename: Jiang-Rui
authors.initials: JR
authors.lastname: Zhou
authors.forename: Ding-Ya
authors.initials: DY
authors.lastname: Sun
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Huang
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Wang
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Jiang
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors; D003863:Depression / Q000139:chemically induced* / Q000150:complications* / Q000517:prevention & control; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005518:Food Preferences / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000209:etiology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012333:RNA, Messenger / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D012333:RNA, Messenger; D013395:Sucrose; D020170:Caspase 1
keywords: Cytokines; Depression; Inflammation; Interleukin-1β; NLRP3 inflammasome