Effect of nerve growth factor on synaptic depression after axotomy

It is reported here that exogenous NGF can, to a large extent, prevent the synaptic depression seen in adult sympathetic ganglion cells after interruption of their axons.

Abstract

INTERRUPTION of the axon of a mammalian nerve cell leads to severe depression of synaptic transmission to the affected neurone within a few days, due primarily to loss of synaptic contacts1–4. In the superior cervical ganglion of the guinea pig, recovery of synaptic contacts on many neurones occurs if axon regeneration is allowed, but generally does not take place after axon ligation4. Furthermore, application of colchicine to postganglionic nerves causes synaptic loss in the absence of mechanical axon interruption5 (see also ref. 6). These findings indicate that axonal extension to the periphery in some way provides the parent neurone with a 'trophic' signal which is instrumental in maintaining preganglionic synaptic contacts. In the sympathetic nervous system the protein nerve growth factor (NGF) has a number of effects on the metabolism and morphology of developing neurones whose survival is ultimately dependent on the presence of this agent7. One mechanism by which NGF affects neurones is an interaction with specific surface receptors on cell bodies8. More recent experiments have supported the suggestion9 that NGF may also act as a messenger from the effector organ to innervating sympathetic neurones: NGF is selectively taken up by sympathetic endings10, can be retrogradely transported to the neuronal somata10,11, and has been shown to prevent some of the biochemical changes that follow axotomy in young animals12,13. Thus a natural question to ask is whether NGF might be involved in the regulation of synapses on mature ganglion cells. We report here that exogenous NGF can, to a large extent, prevent the synaptic depression seen in adult sympathetic ganglion cells after interruption of their axons.