NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide

Wei Zhu, Feng Sheng Cao, Jun Feng, Hua Weng Chen, Jie Ru Wan, Qing Lu, Jian Wang

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5 mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalNeuroscience
Volume343
DOIs
StatePublished - Feb 20 2017

Keywords

  • LPS
  • NLRP3 inflammasome
  • depression
  • forced swim test
  • recognition memory
  • tail suspension test

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint

Dive into the research topics of 'NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide'. Together they form a unique fingerprint.

Cite this