NEUROTROPHIN-3 ENHANCES NEURITE OUTGROWTH IN CULTURED HIPPOCAMPAL PYRAMIDAL NEURONS

Low density dissociated cultures of embryonic rat hippocampal cells we re used to study the effects of neurotrophin-3 (NT-3) on neuronal morp hogenesis. The results obtained indicate that NT-3 enhances neurite ou tgrowth and branching; this is a dose-dependent effect, detected in ap proximately 50% of the neurons, and prevented by K-252a, an inhibitor of the trk family of receptor protein kinases. NT-3 also accelerates t he development of neuronal polarity, a phenomenon preceded by a dramat ic accumulation of bundles of looped microtubules within axonal growth cones; these microtubule bundles contain tyrosinated, detyrosinated, and acetylated a-tubulin. Taken collectively, our data suggest that ev en though the basic shape of hippocampal neurons may be endogenously d etermined, critical aspects of their morphological development may be modulated by trophic factors such as NT-3. In addition, our observatio ns suggest that at least some of the neuritogenic effects of NT-3 invo lve a stimulation of microtubule assembly and/or transport. (C) 1994 W iley-Liss, Inc.