title: Role of brain transmigrating neutrophils in depression-like behavior during systemic infection.
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.
authors.forename: A
authors.initials: A
authors.lastname: Aguilar-Valles
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Aguliar-Valles
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Jung
authors.affiliation: Groupe de recherche en neurobiologie comportementale/Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Woodside
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
authors.forename: G N
authors.initials: GN
authors.lastname: Luheshi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000276:immunology*; D007155:Immunologic Factors / Q000494:pharmacology; D007239:Infections / Q000188:drug therapy / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009765:Obesity / Q000188:drug therapy / Q000276:immunology
chemical_list: C587672:IL1B protein, mouse; D007155:Immunologic Factors; D053583:Interleukin-1beta; D020738:Leptin; D008070:Lipopolysaccharides