Neurodegeneration by activation of the microglial complement-phagosome pathway

Bodea, Liviu-Gabriel, Wang, Yiner, Linnartz-Gerlach, Bettina, Kopatz, Jens, Sinkkonen, Lasse, Musgrove, Ruth, Kaoma, Tony, Muller, Arnaud, Vallar, Laurent, Di Monte, Donato A., Balling, Rudi and Neumann, Harald (2014) Neurodegeneration by activation of the microglial complement-phagosome pathway. Journal of Neuroscience, 34 25: 8546-8556. doi:10.1523/JNEUROSCI.5002-13.2014

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Author Bodea, Liviu-Gabriel
Wang, Yiner
Linnartz-Gerlach, Bettina
Kopatz, Jens
Sinkkonen, Lasse
Musgrove, Ruth
Kaoma, Tony
Muller, Arnaud
Vallar, Laurent
Di Monte, Donato A.
Balling, Rudi
Neumann, Harald
Title Neurodegeneration by activation of the microglial complement-phagosome pathway
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 1529-2401
Publication date 2014-06-01
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.5002-13.2014
Open Access Status File (Publisher version)
Volume 34
Issue 25
Start page 8546
End page 8556
Total pages 11
Place of publication Washington DC United States
Publisher Society for Neuroscience
Language eng
Abstract Systemic inflammatory reactions have been postulated to exacerbate neurodegenerative diseases via microglial activation. We now demonstrate in vivo that repeated systemic challenge of mice over four consecutive days with bacterial LPS maintained an elevated microglial inflammatory phenotype and induced loss of dopaminergic neurons in the substantia nigra. The same total cumulative LPS dose given within a single application did not induce neurodegeneration. Whole-genome transcriptome analysis of the brain demonstrated that repeated systemic LPS application induced an activation pattern involving the classical complement system and its associated phagosome pathway. Loss of dopaminergic neurons induced by repeated systemic LPS application was rescued in complement C3-deficient mice, confirming the involvement of the complement system in neurodegeneration. Our data demonstrate that a phagosomal inflammatory response of microglia is leading to complement-mediated loss of dopaminergic neurons.
Keyword Complement
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
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