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

Molecular Psychiatry volume 19, pages 599–606 (2014)Cite this article

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A Corrigendum to this article was published on 03 February 2015

A Corrigendum to this article was published on 05 November 2013

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.

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Acknowledgements

We thank Dr Stephen Poole (National Institute for Biological Standards and Control, Hertfordshire, UK), for kindly providing the LAS. We are grateful to Dr Hymie Anisman and Dr Wataru Inoue for the critical reading of this manuscript and to Miss Ke Cui for excellent technical assistance. This work was supported by CIHR and NSERC grants to GNL.

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  1. A Aguliar-Valles

    Present address: 3Current address: Department of Physiology, Université de Montréal and Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.,

Authors and Affiliations

  1. Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada

    A Aguliar-Valles, J Kim, S Jung & G N Luheshi

  2. Groupe de recherche en neurobiologie comportementale/Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada

    B Woodside

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Aguliar-Valles, A., Kim, J., Jung, S. et al. Role of brain transmigrating neutrophils in depression-like behavior during systemic infection. Mol Psychiatry 19, 599–606 (2014). https://doi.org/10.1038/mp.2013.137

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