Role of brain transmigrating neutrophils in depression-like behavior during systemic infection

Mol Psychiatry. 2014 May;19(5):599-606. doi: 10.1038/mp.2013.137. Epub 2013 Oct 15.

Abstract

Peripheral inflammation induces transmigration of interleukin (IL)-1β-expressing neutrophils to the brain. We investigated the possibility that this presents a new route of immune-to-brain communication by assessing their role in sickness behaviors relevant for mood disorders. Mice treated with lipopolysaccharide (LPS) developed despair-like behavior, and administration of an anti-polymorphonuclear antibody abolished LPS-induced despair-like and asocial behaviors, which correlated with the levels of IL-1β expression in the brain. These behavioral changes were directly mediated by the energy-regulating hormone, leptin. Increasing the concentration of endogenous leptin during obesity exacerbated, whereas its neutralization using a specific antiserum attenuated sickness behaviors and importantly the neutrophil transmigrating process. Our results indicate a role for peripheral neutrophils in conveying inflammatory signals to the brain, which appears to be dependent on the energy status of the organism. This constitutes a novel mechanism of immune-to-brain communication relevant to mood disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / immunology*
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Depression / drug therapy
  • Depression / immunology*
  • Immunologic Factors / pharmacology
  • Infections / drug therapy
  • Infections / immunology*
  • Interleukin-1beta / metabolism
  • Leptin / metabolism
  • Lipopolysaccharides
  • Male
  • Mice, Inbred C57BL
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology*
  • Neutrophils / drug effects
  • Neutrophils / physiology*
  • Obesity / drug therapy
  • Obesity / immunology

Substances

  • IL1B protein, mouse
  • Immunologic Factors
  • Interleukin-1beta
  • Leptin
  • Lipopolysaccharides