NEUROTROPHIC INFLUENCE OF DENERVATED SCIATIC-NERVE ON ADULT DORSAL-ROOT GANGLION NEURONS

Isolated adult frog dorsal root ganglion neurons survive in vitro in a defined medium for more than 4 weeks and extend processes. When co-cu ltured with a 1-mm piece of peripheral nerve the average total process length per neuron was 10 times longer than that of control neurons by 8 days, and the processes had a significantly different morphology fr om that of control neurons. This influence on process length increased with increasing time of nerve denervation prior to co-culturing. Thes e results suggest the release of a neurotrophic factor/s from the cell s of the peripheral nerve. The neurotrophic influence was completely b locked by antibodies against mouse nerve growth factor (NGF). Although NGF increased the average process length by twofold over control neur ons, its influence never reached that of the nerve-released factor, an d the NGF-induced processes had a distinctly different morphology. The frog nerve-released factor promoted process outgrowth from Ell chick sympathetic ganglia, although the process number, length, and their fa sciculation differed greatly from those induced by NGF. These results suggest that the nerve-released factor/s are immunologically and funct ionally related to NGF but have not established whether a single facto r or an aggregate of several secreted molecules are responsible. This article presents a new preparation in which the varied influences of d ifferent neurotrophic factors can be studied in great detail on large populations of isolated adult vertebrate neurons and sets the stage fo r the characterization and isolation of the frog peripheral nerve neur otrophic factor, as well as examining the influence of this factor on neuronal morphology and its ability to direct process outgrowth. (C) 1 994 John Wiley and Sons, Inc.