Specificity of retrograde transport of nerve growth factor (NGF) in sensory neurons: a biochemical and morphological study

Abstract

In previous studies it has been shown that nerve growth factor (NGF) is taken up with a high selectivity by adrenergic nerve terminals and is transported retrogradely to the perikaryon11,22. It was the aim of the present experiments to investigate whether the sensory neurons exhibit the same high degree of selectivity for retrograde transport throughout the whole life cycle, although it is known that their dramatic response to NGF is confined to a short period of ontogenetic development. Unilateral injection of [125I]NGF into the forepaw of adult rats was followed by a preferential accumulation of radioactivity in the sensory ganglia (C6-C7) of the injected side. However, this preferential accumulation was not detectable earlier than 6 h after injection and reached a maximum (ratio between injected and non-injected side, 5:1) after 11-16 h. Transection of the plexus brachialis abolished and local administration of colchicine prior to that of [125I]NGF greatly reduced the preferential accumulation of radioactivity in the ganglia of the injected side. The rate of retrograde transport of NGF in sensory neurons was calculated to be 13 mm/h which is about 5 times faster than that in adrenergic neurons. The selectivity of this retrograde transport was demonstrated by the fact that injection of 125I-labeled bovine serum albumin and cytochrome c did not result in a preferential accumulation of radioactivity in the sensory ganglia of the injected side. Light microscopic autoradiography revealed heavily labeled cells in the sensory ganglia (C6-C7) of the injected side after administration of [125I]NGF into the forepaw. Only cells belonging to the large cell type were labeled. Prolonged (7 mug/g/day over 5 days) injection of NGF into the forepaw of 10-day-old rats did not result in a hypertropic response of the sensory neurons as far as can be judged from morphometric studies at the light microscopic level.