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@ARTICLE{Bodea:137449,
author = {Bodea, Liviu-Gabriel and Wang, Yiner and Linnartz-Gerlach,
Bettina and Kopatz, Jens and Sinkkonen, Lasse and Musgrove,
Ruth and Kaoma, Tony and Muller, Arnaud and Vallar, Laurent
and Di Monte, Donato A and Balling, Rudi and Neumann,
Harald},
title = {{N}eurodegeneration by activation of the microglial
complement-phagosome pathway.},
journal = {The journal of neuroscience},
volume = {34},
number = {25},
issn = {0270-6474},
address = {Washington, DC},
publisher = {Soc.57413},
reportid = {DZNE-2020-03771},
pages = {8546-8556},
year = {2014},
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.},
keywords = {Animals / Complement Activation: physiology / Complement
C3: metabolism / Complement System Proteins: physiology /
Dopaminergic Neurons: metabolism / Dopaminergic Neurons:
pathology / Male / Mice / Mice, 129 Strain / Mice, Inbred
C57BL / Mice, Knockout / Microglia: metabolism / Microglia:
pathology / Nerve Degeneration: metabolism / Nerve
Degeneration: pathology / Neural Pathways: physiology /
Phagosomes: metabolism / Phagosomes: pathology / Phagosomes:
physiology / Complement C3 (NLM Chemicals) / Complement
System Proteins (NLM Chemicals)},
cin = {AG Di Monte},
ddc = {610},
cid = {I:(DE-2719)1013008},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:24948809},
pmc = {pmc:PMC6608212},
doi = {10.1523/JNEUROSCI.5002-13.2014},
url = {https://pub.dzne.de/record/137449},
}