NEUROTROPHINS REGULATE THE FUNCTION OF CULTURED MICROGLIA

Although the physiological role of neurotrophins in neuronal developme nt and survival has been extensively investigated, their role in glial cell physiology remains to be elucidated. In the present; study, we i nvestigated the effects of neurotrophins on cultured microglia from ne wborn rat brain. All of the neurotrophins tested nerve growth factor ( NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), increased the secretion of plasminogen and urokinase type-plasminogen activator and specific activity of acid ph osphatase, but suppressed the release of constitutively-produced and l ipopolysaccharide-stimulated nitric oxide (NO) from microglia. The rev erse transcription-polymerase chain reaction, immunocytochemical stain ing, and Western blotting revealed that cultured microglia express Trk A, B, and C, and low-affinity NGF receptor, LNGFRp75. Neurotrophin wa s found to phosphorylate Trk A and B, and the neurotrophin-induced enh ancement of plasminogen-secretion was suppressed by protein kinase inh ibitor, K252a. Furthermore, neurotrophins caused an activation of tran scription factor, NF-kappa B. These results indicate that the neurotro phin family regulate the function of microglia through Trk and/or LNGF Rp75-mediated signal transduction. (C) 1998 Wiley-Liss, Inc.