FGF-2 released from degenerating neurons exerts microglial-induced neuroprotection via FGFR3-ERK signaling pathway.
J Neuroinflammation
; 11: 76, 2014 Apr 16.
Article
em En
| MEDLINE
| ID: mdl-24735639
ABSTRACT
BACKGROUND:
The accumulation of activated microglia is a hallmark of various neurodegenerative diseases. Microglia may have both protective and toxic effects on neurons through the production of various soluble factors, such as chemokines. Indeed, various chemokines mediate the rapid and accurate migration of microglia to lesions. In the zebra fish, another well-known cellular migrating factor is fibroblast growth factor-2 (FGF-2). Although FGF-2 does exist in the mammalian central nervous system (CNS), it is unclear whether FGF-2 influences microglial function.METHODS:
The extent of FGF-2 release was determined by ELISA, and the expression of its receptors was examined by immunocytochemistry. The effect of several drug treatments on a neuron and microglia co-culture system was estimated by immunocytochemistry, and the neuronal survival rate was quantified. Microglial phagocytosis was evaluated by immunocytochemistry and quantification, and microglial migration was estimated by fluorescence-activated cell sorting (FACS). Molecular biological analyses, such as Western blotting and promoter assay, were performed to clarify the FGF-2 downstream signaling pathway in microglia.RESULTS:
Fibroblast growth factor-2 is secreted by neurons when damaged by glutamate or oligomeric amyloid ß 1-42. FGF-2 enhances microglial migration and phagocytosis of neuronal debris, and is neuroprotective against glutamate toxicity through FGFR3-extracellular signal-regulated kinase (ERK) signaling pathway, which is directly controlled by Wnt signaling in microglia.CONCLUSIONS:
FGF-2 secreted from degenerating neurons may act as a 'help-me' signal toward microglia by inducing migration and phagocytosis of unwanted debris.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fator 2 de Crescimento de Fibroblastos
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Microglia
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Sistema de Sinalização das MAP Quinases
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Receptor Tipo 3 de Fator de Crescimento de Fibroblastos
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Degeneração Neural
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article