Journal Article

DZNE-2020-03771

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neurodegeneration by activation of the microglial complement-phagosome pathway.

Bodea, L.-G. ; Wang, Y. ; Linnartz-Gerlach, B. ; Kopatz, J. ; Sinkkonen, L. ; Musgrove, R.DZNE* ; Kaoma, T. ; Muller, A. ; Vallar, L. ; Di Monte, D. A.DZNE* ; Balling, R. ; Neumann, H. (Corresponding author)

2014
Soc.57413 Washington, DC

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Please use a persistent id in citations: doi:10.1523/JNEUROSCI.5002-13.2014

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.

Keyword(s): Animals (MeSH) ; Complement Activation: physiology (MeSH) ; Complement C3: metabolism (MeSH) ; Complement System Proteins: physiology (MeSH) ; Dopaminergic Neurons: metabolism (MeSH) ; Dopaminergic Neurons: pathology (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, 129 Strain (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Microglia: metabolism (MeSH) ; Microglia: pathology (MeSH) ; Nerve Degeneration: metabolism (MeSH) ; Nerve Degeneration: pathology (MeSH) ; Neural Pathways: physiology (MeSH) ; Phagosomes: metabolism (MeSH) ; Phagosomes: pathology (MeSH) ; Phagosomes: physiology (MeSH) ; Complement C3 ; Complement System Proteins

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Contributing Institute(s):

1. Neurodegeneration and Neuroprotection in Parkinson´s Disease (AG Di Monte)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2014

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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