Reference : Neurodegeneration by Activation of the Microglial Complement–Phagosome Pathway
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/17019
Neurodegeneration by Activation of the Microglial Complement–Phagosome Pathway
English
Bodea, Liviu-Gabriel [University of Bonn > Institute of Reconstructive Neurobiology > Neural Regeneration Group,]
Wang, Yiner [University of Bonn > Institute of Reconstructive Neurobiology > Neural Regeneration Group]
Linnartz-Gerlach, Bettina [University of Bonn > Institute of Reconstructive Neurobiology > Neural Regeneration Group]
Kopatz, Jens [University of Bonn > Institute of Reconstructive Neurobiology > Neural Regeneration Group]
Sinkkonen, Lasse mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)]
Musgrove, Ruth [German Center for Neurodegenerative Diseases]
Kaoma, Tony [CRP-Sante > Genomics Research Unit]
Muller, Arnaud [CRP-Sante > Genomics Research Unit]
Vallar, Laurent [CRP-Sante > Genomics Research Unit]
Di Monte, Donato [German Center for Neurodegenerative Diseases]
Balling, Rudi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Neumann, Harald [University of Bonn > Institute of Reconstructive Neurobiology > Neural Regeneration Group]
18-Jun-2014
Journal of Neuroscience
Society for Neuroscience
34
25
8546-8556
Yes (verified by ORBilu)
International
0270-6474
1529-2401
Washington
DC
[en] complement ; microglia ; neurodegeneration ; neuroinflammation ; phagosome ; transcriptome
[en] 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.
Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
http://hdl.handle.net/10993/17019
10.1523/JNEUROSCI.5002-13.2014
http://www.jneurosci.org/content/34/25/8546.short

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