Role of brain transmigrating neutrophils in depression-like behavior during systemic infection.
|Title||Role of brain transmigrating neutrophils in depression-like behavior during systemic infection.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Aguilar-Valles A, Aguliar-Valles A, Kim J, Jung S, Woodside B, Luheshi G|
|Date Published||2014 May|
|Keywords||Animals, Brain, Cell Movement, Depression, Immunologic Factors, Infection, Interleukin-1beta, Leptin, Lipopolysaccharides, Male, Mice, Inbred C57BL, Neuroimmunomodulation, Neutrophils, Obesity|
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.
|Alternate Journal||Mol. Psychiatry|
|Grant List||/ / Canadian Institutes of Health Research / Canada|