Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide production and neurodegeneration
E Colombo, C Cordiglieri, G Melli… - Journal of Experimental …, 2012 - rupress.org
Journal of Experimental Medicine, 2012•rupress.org
Neurotrophin growth factors support neuronal survival and function. In this study, we show
that the expression of the neurotrophin receptor TrkB is induced on astrocytes in white
matter lesions in multiple sclerosis (MS) patients and mice with experimental autoimmune
encephalomyelitis (EAE). Surprisingly, mice lacking TrkB specifically in astrocytes were
protected from EAE-induced neurodegeneration. In an in vitro assay, astrocytes stimulated
with the TrkB agonist brain-derived neurotrophic factor (BDNF) released nitric oxide (NO) …
that the expression of the neurotrophin receptor TrkB is induced on astrocytes in white
matter lesions in multiple sclerosis (MS) patients and mice with experimental autoimmune
encephalomyelitis (EAE). Surprisingly, mice lacking TrkB specifically in astrocytes were
protected from EAE-induced neurodegeneration. In an in vitro assay, astrocytes stimulated
with the TrkB agonist brain-derived neurotrophic factor (BDNF) released nitric oxide (NO) …
Neurotrophin growth factors support neuronal survival and function. In this study, we show that the expression of the neurotrophin receptor TrkB is induced on astrocytes in white matter lesions in multiple sclerosis (MS) patients and mice with experimental autoimmune encephalomyelitis (EAE). Surprisingly, mice lacking TrkB specifically in astrocytes were protected from EAE-induced neurodegeneration. In an in vitro assay, astrocytes stimulated with the TrkB agonist brain-derived neurotrophic factor (BDNF) released nitric oxide (NO), and conditioned medium from activated astrocytes had detrimental effects on the morphology and survival of neurons. This neurodegenerative process was amplified by NO produced by neurons. NO synthesis in the central nervous system during EAE depended on astrocyte TrkB. Together, these findings suggest that TrkB expression on astrocytes may represent a new target for neuroprotective therapies in MS.
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