Involvement of inflammasome activation in lipopolysaccharide-induced mice depressive-like behaviors

CNS Neurosci Ther. 2014 Feb;20(2):119-24. doi: 10.1111/cns.12170. Epub 2013 Nov 27.


Aims: 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.

Conclusion: 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.

Keywords: Cytokines; Depression; Inflammation; Interleukin-1β; NLRP3 inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / administration & dosage*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cysteine Proteinase Inhibitors
  • Depression / chemically induced*
  • Depression / complications*
  • Depression / prevention & control
  • Disease Models, Animal
  • Drug Administration Schedule
  • Food Preferences / drug effects
  • Gene Expression Regulation / drug effects*
  • Inflammation / etiology*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • RNA, Messenger / metabolism
  • Sucrose / administration & dosage
  • Swimming / psychology


  • Amino Acid Chloromethyl Ketones
  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • Interleukin-1beta
  • Lipopolysaccharides
  • N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • RNA, Messenger
  • Sucrose
  • Caspase 1