Axon retraction following guanethidine treatment: studies of sympathetic neurons in tissue culture

Summary

The ultrastructural appearance of cultured sympathetic nerve cell bodies and axons during guanethidine-induced retraction of axons has been described and correlated with phase contrast microscopic observations. In retracting axons, morphological alterations (notably aggregation of smooth membranous tubules and formation of myeloid whorls) occurred in swellings, which appeared to correspond to varicosities. Intervaricose regions of axons showed no significant changes; the organization of neurotubules and neurofilaments appeared to be normal. Axonal mitochondria were apparently undamaged, except in regions close to their cell bodies. In the cell bodies of sympathetic neurons, the early phase of degeneration was characterized by specific mitochondrial damage accompanied by some loss of free ribosomes and rough endoplasmic reticulum. This was followed by a second phase in the cell bodies in which there was substantial accumulation of myeloid whorls and organelles, including neurotubules and neurofilaments. It is suggested that this accumulation has resulted from transfer of some of the contents of the axons to the cell body as a consequence of axon retraction. The morphological features of these two proposed phases bear striking resemblance to ultrastructural alterations characteristic of the first two phases of degeneration of adrenergic neuronsin vivo after guanethidine treatment. Various possibilities are discussed concerning the mechanism underlying guanethidine-induced axon retraction.