Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival.
J Exp Med
; 210(1): 157-72, 2013 Jan 14.
Article
em En
| MEDLINE
| ID: mdl-23296467
ABSTRACT
Colony-stimulating factor 1 (CSF1) and interleukin-34 (IL-34) are functional ligands of the CSF1 receptor (CSF1R) and thus are key regulators of the monocyte/macrophage lineage. We discovered that systemic administration of human recombinant CSF1 ameliorates memory deficits in a transgenic mouse model of Alzheimer's disease. CSF1 and IL-34 strongly reduced excitotoxin-induced neuronal cell loss and gliosis in wild-type mice when administered systemically before or up to 6 h after injury. These effects were accompanied by maintenance of cAMP responsive element-binding protein (CREB) signaling in neurons rather than in microglia. Using lineage-tracing experiments, we discovered that a small number of neurons in the hippocampus and cortex express CSF1R under physiological conditions and that kainic acid-induced excitotoxic injury results in a profound increase in neuronal receptor expression. Selective deletion of CSF1R in forebrain neurons in mice exacerbated excitotoxin-induced death and neurodegeneration. We conclude that CSF1 and IL-34 provide powerful neuroprotective and survival signals in brain injury and neurodegeneration involving CSF1R expression on neurons.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Estimulador de Colônias de Macrófagos
/
Receptor de Fator Estimulador de Colônias de Macrófagos
/
Neurônios
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos