Stress-Induced Depressive Behaviors Require a Functional NLRP3 Inflammasome

Mol Neurobiol. 2016 Sep;53(7):4874-82. doi: 10.1007/s12035-015-9408-7. Epub 2015 Sep 11.

Abstract

Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients.

Keywords: Depression; Inflammasome; Microglia; Stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Depression / metabolism*
  • Depression / pathology
  • Depression / psychology
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Inflammasomes / deficiency*
  • Interpersonal Relations
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / metabolism
  • Microglia / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein / deficiency*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / pathology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology
  • Stress, Psychological / psychology

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse