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Updated: Dec 20, 2025
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats
Elisabeth G Vichaya1,2, Sajida Malik3, Luba Sominsky3
1Department of Symptom Research, University of Texas MD Anderson Cancer Center, Unit 1055 6565 MD Anderson Boulevard, Houston, TX, 77030, USA.
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.
Insights
Microglia activation is not essential for sickness behavior during acute inflammation. Removing microglia did not prevent, and even worsened, sickness responses to lipopolysaccharide (LPS) in mice and rats.
Area of Science:
- Neuroimmunology
- Neuroinflammation
Background:
- Microglia are believed to mediate sickness behavior via inflammatory mediators.
- Systemic inflammation triggers reactive microglial cells in the brain.
Purpose of the Study:
- To investigate the role of microglia in sickness behavior.
- To determine if microglia are essential for sickness responses to lipopolysaccharide (LPS).
Main Methods:
- Microglia were depleted in mice using PLX5622 (CSF-1R antagonist) and in rats via diphtheria toxin in CX3CR1-DTR model.
- Mice and rats received LPS or saline injection to induce sickness.
- Sickness was quantified by body weight loss, locomotor activity, and wheel running.
Main Results:
- Microglia and peripheral macrophages were successfully depleted.
- LPS still induced proinflammatory cytokine expression in the brain, and even exacerbated it in some cases.
- LPS-induced sickness behavior, measured by wheel running, was not abrogated but exacerbated in mice.
Conclusions:
- Microglia activation is not required for the development of sickness behavior.
- Sickness-inducing effects of acute inflammation can occur independently of microglia.
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