BRAIN-DERIVED NEUROTROPHIC FACTOR INDUCES A RAPID UP-REGULATION OF SYNAPTOPHYSIN AND TAU-PROTEINS VIA THE NEUROTROPHIN RECEPTOR TRKB IN RATCEREBELLAR GRANULE CELLS

We have examined the effects of neurotrophins brain derived neurotroph ic factor (BDNF) and nerve growth factor (NGF) on the expression of th e maturation-specific proteins synaptophysin end tau, and the growth-a ssociated protein (GAP)-43 in cerebellar granule cells. We find that B DNF but not NGF rapidly (within 2 h) upregulates levels of synaptophys in, tau and c-Fos correlating with expression of the neurotrophin rece ptor TrkB. The rapid increase in synaptophysin is not preceded by c-Fo s elevation suggesting a post-transcriptional mechanism may be involve d. In contrast, no upregulation of GAP-43 levels are seen within this time period. Phorbol ester mimics the effects of BDNF, indicating that protein kinase C (PKC) is either a component of, or feeds into the si gnalling mechanism. We conclude that BDNF, characterized to be surviva l promoting early in differentiation of cerebellar granule cells, enha nces maturation at a later stage. (C) 1997 Elsevier Science Ireland Lt d.