Details

Autor(en) / Beteiligte

• 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

Titel

Neurodegeneration by activation of the microglial complement-phagosome pathway

Ist Teil von

• The Journal of neuroscience, 2014-06, Vol.34 (25), p.8546-8556

Ort / Verlag

United States: Society for Neuroscience

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.