MOUSE ASTROCYTES STORE AND DELIVER BRAIN-DERIVED NEUROTROPHIC FACTOR USING THE NONCATALYTIC GP95(TRKB) RECEPTOR

A study of the brain-derived neurotrophic factor (BDNF)-binding capaci ty of pure astrocytes demonstrated that these cells bind and endocytos e [I-125]BDNF rapidly using the gp95(trkB) truncated receptor. A linea r Scatchard plot indicated the presence of only one type of receptor t hat bound the ligand, with a low K-d of 1.24 x 10(-8) M. There were an average of 36 468 copies of this receptor on untreated astrocytes. In terestingly, the neurotrophin was not degraded intracellularly, as dem onstrated by HPLC experiments. Furthermore, the stored molecule was re leased by a mechanism regulated by the extracellular BDNF concentratio n as a bioactive neurotrophic molecule that supports neuron survival, in a time-and temperature-dependent manner. The data demonstrate that astrocytes exert an active role in the bioavailability of this neurotr ophin, which is further enhanced in an inflammatory-like situation ind uced experimentally in culture using interferon-gamma.