Artículo de revista
Production of nerve growth factor by β-amyloid-stimulated astrocytes induces p75NTR-dependent tau hyperphosphorylation in cultured hippocampal neurons
Fecha
2006Registro en:
Journal of Neuroscience Research, Volumen 84, Issue 5, 2018, Pages 1098-1106
03604012
10974547
10.1002/jnr.20996
Autor
Sáez, Estefanía T.
Pehar, Mariana
Vargas, Marcelo R.
Barbeito, Luis
Maccioni Baraona, Ricardo
Institución
Resumen
Reactive astrocytes surround amyloid depositions and degenerating neurons in Alzheimer's disease (AD). It has been previously shown that β-amyloid peptide induces inflammatory-like responses in astrocytes, leading to neuronal pathology. Reactive astrocytes up-regulate nerve growth factor (NGF), which can modulate neuronal survival by signaling through TrkA or p75 neurotrophin receptor (p75NTR). Here, we analyzed whether soluble Aβ peptide 25-35 (Aβ) stimulated astrocytic NGF expression, modulating the survival of cultured embryonic hippocampal neurons. Hippocampal astrocytes incubated with Aβ up-regulated NGF expression and release to the culture medium. Aβ-stimulated astrocytes increased tau phosphorylation and reduced the survival of cocultured hippocampal neurons. Neuronal death and tau phosphorylation were reproduced by conditioned media from Aβ-stimulated astrocytes and prevented by caspase inhibitors or blocking antibodies to NGF or p75NTR. Moreover, exogenous NGF was sufficient