TY  - JOUR
AU  - Bodea, Liviu-Gabriel
AU  - Wang, Yiner
AU  - Linnartz-Gerlach, Bettina
AU  - Kopatz, Jens
AU  - Sinkkonen, Lasse
AU  - Musgrove, Ruth
AU  - Kaoma, Tony
AU  - Muller, Arnaud
AU  - Vallar, Laurent
AU  - Di Monte, Donato A
AU  - Balling, Rudi
AU  - Neumann, Harald
TI  - Neurodegeneration by activation of the microglial complement-phagosome pathway.
JO  - The journal of neuroscience
VL  - 34
IS  - 25
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.57413
M1  - DZNE-2020-03771
SP  - 8546-8556
PY  - 2014
AB  - 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.
KW  - Animals
KW  - Complement Activation: physiology
KW  - Complement C3: metabolism
KW  - Complement System Proteins: physiology
KW  - Dopaminergic Neurons: metabolism
KW  - Dopaminergic Neurons: pathology
KW  - Male
KW  - Mice
KW  - Mice, 129 Strain
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Microglia: metabolism
KW  - Microglia: pathology
KW  - Nerve Degeneration: metabolism
KW  - Nerve Degeneration: pathology
KW  - Neural Pathways: physiology
KW  - Phagosomes: metabolism
KW  - Phagosomes: pathology
KW  - Phagosomes: physiology
KW  - Complement C3 (NLM Chemicals)
KW  - Complement System Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24948809
C2  - pmc:PMC6608212
DO  - DOI:10.1523/JNEUROSCI.5002-13.2014
UR  - https://pub.dzne.de/record/137449
ER  -