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

Vichaya, Elisabeth G, Malik, Sajida, Sominsky, Luba, Ford, Bianca G, Spencer, Sarah J and Dantzer, Robert 2020, Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats, Journal of neuroinflammation, vol. 17, no. 1, pp. 1-14, doi: 10.1186/s12974-020-01832-2.

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Title Microglia depletion fails to abrogate inflammation-induced sickness in mice and rats
Author(s) Vichaya, Elisabeth G
Malik, Sajida
Sominsky, Luba
Ford, Bianca G
Spencer, Sarah J
Dantzer, Robert
Journal name Journal of neuroinflammation
Volume number 17
Issue number 1
Article ID 172
Start page 1
End page 14
Total pages 14
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2020
ISSN 1742-2094
1742-2094
Keyword(s) ACTIVATION
BEHAVIOR
BRAIN
CELL ABLATION
CSF-1 receptor antagonism
Cx3cr1
Diphtheria toxin
DIPHTHERIA-TOXIN RECEPTOR
ELIMINATION
EXPRESSION
Immunology
Inflammation
INTERLEUKIN-1-BETA
Life Sciences & Biomedicine
Lipopolysaccharide
MESSENGER-RNA
Microglia
Mouse
Neurosciences
Neurosciences & Neurology
PATTERNS
PLX5622
Rat
Running wheel activity
Science & Technology
Sickness
Summary 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. ConclusionsThese findings reveal that the sickness-inducing effects of acute inflammation can develop independently of microglia activation.
Language eng
DOI 10.1186/s12974-020-01832-2
Indigenous content off
Field of Research 1103 Clinical Sciences
1107 Immunology
1109 Neurosciences
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30150209

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.