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

• Published in: Molecular psychiatry Vol. 19; no. 5; p. 633
• Main Authors: Aguliar-Valles, A, Kim, J, Jung, S, Woodside, B, Luheshi, G.N
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 01-05-2014
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2013.154

Peripheral inflammation induces transmigration of interleukin (IL)-1[beta]-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-1[beta] 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.