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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2020

Open Access 01-12-2020 | Cytokines | Research

Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats

Authors: Elisabeth G. Vichaya, Sajida Malik, Luba Sominsky, Bianca G. Ford, Sarah J. Spencer, Robert Dantzer

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

Background

Production of inflammatory mediators by reactive microglial cells in the brain is generally considered the primary mechanism underlying the development of symptoms of sickness in response to systemic inflammation.

Methods

Depletion of microglia was achieved in C57BL/6 mice by chronic oral administration of PLX5622, a specific antagonist of colony stimulating factor-1 receptor, and in rats by a knock-in model in which the diphtheria toxin receptor was expressed under the control of the endogenous fractalkine receptor (CX3CR1) promoter sequence. After successful microglia depletion, mice and rats were injected with a sickness-inducing dose of lipopolysaccharide according to a 2 (depletion vs. control) × 2 (LPS vs. saline) factorial design. Sickness was measured by body weight loss and decreased locomotor activity in rats and mice, and reduced voluntary wheel running in mice.

Results

Chronic administration of PLX5622 in mice and administration of diphtheria toxin to knock-in rats depleted microglia and peripheral tissue macrophages. However, it did not abrogate the inducible expression of proinflammatory cytokines in the brain in response to LPS and even exacerbated it for some of the cytokines. In accordance with these neuroimmune effects, LPS-induced sickness was not abrogated, rather it was exacerbated when measured by running wheel activity in mice.

Conclusions

These findings reveal that the sickness-inducing effects of acute inflammation can develop independently of microglia activation.
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Metadata
Title
Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats
Authors
Elisabeth G. Vichaya
Sajida Malik
Luba Sominsky
Bianca G. Ford
Sarah J. Spencer
Robert Dantzer
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-01832-2

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