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.
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The breakdown of the blood-brain barrier produced by peripheral immune challenge (lipopolysaccharide) permits passage of bone marrow-derived immune cells into the brain, a process enhanced by diet-induced obesity and that favors depressive behaviors.
“The breakdown of the BBB produced by peripheral immune challenge (LPS) permits passage of bone marrow-derived immune cells into the brain, a process enhanced by DIO [163] and that favors depressive behaviors [164,165].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [165]
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References 66 · Cited by 97
- Authors
- Aguliar-Valles, A., Kim, J., Jung, S., Woodside, B., & Luheshi, G. N.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Concordia University (CA)
- Corresponding author
- Luheshi, G N
- Venue
- Molecular Psychiatry
- Published
- 2013-10-15
- Volume
- 19
- Issue
- 5
- Pages
- 599-606
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2015725986
- Cited by
- 97
- References
- 66
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 5 · 2016: 8 · 2015: 10 · 2014: 6
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Update notices
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- neutrophil transmigration, depression-like behavior, sickness behavior, systemic infection, lipopolysaccharide, IL-1β, leptin, asocial behavior, obesity, mood disorders, peripheral inflammation
- MeSH terms
- Animals, Brain, Cell Movement, Depression, Immunologic Factors, Infections, Lipopolysaccharides, Male, Mice, Inbred C57BL, Neutrophils, Obesity, Neuroimmunomodulation, Leptin, Interleukin-1beta
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