Neurodegeneration by activation of the microglial complement-phagosome pathway.
J Neurosci
; 34(25): 8546-56, 2014 Jun 18.
Article
em En
| MEDLINE
| ID: mdl-24948809
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fagossomos
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Proteínas do Sistema Complemento
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Complemento C3
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Microglia
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Ativação do Complemento
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Neurônios Dopaminérgicos
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Degeneração Neural
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha