EFFECTS OF NERVE GROWTH-FACTOR AND ITS ANTISERUM ON SYNAPSES IN SUPERIOR CERVICAL GANGLION OF GUINEA-PIG

Abstract

The effects of nerve growth factor (NGF) and its antiserum on synapses in the superior cervical ganglion of the guinea pig were examined by intracellular recording and EM. Exogenous NGF, supplied locally from a silicone rubber pellet implanted near ganglia for 4-7 days, had little effect on either the function or the number of ganglionic synapses. However, the depression of synaptic transmission and loss of synaptic contacts on ganglion cells which follow post-ganglionic axotomy were diminished by about 50% in the presence of exogenous NGF. Other post-axotomy changes such as the development of subthreshold regenerative responses in neuronal processes, the appearance of ultrastructurally abnormal neuronal profiles suggesting rapid membrane turnover, and the cytoplasmic and nuclear changes characteristic of chromatolysis, were also largely prevented by exogenous NGF. Systemic treatment of neonatal and young adult guinea pigs with antiserum to NGF for 4-5 days caused depression of intracellularly recorded synaptic responses within 5-8 days of the end of antiserum administration. Synapse counts in EM sections from these ganglia showed only about half as many contacts as in control ganglia from animals receiving normal rabbit serum. The loss of synapses from sympathetic neurons which follows axotomy may result from a reduction in the amount of NGF supplied to ganglion cells. A corollary is that, among other biological roles, NGF is required by peripheral sympathetic neurons to maintain the synapses they receive.