Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons

To investigate the distribution of nerve growth factor (NGF) receptors on peripheral and central axons, [125I]NGF was injected into the sciatic nerve or spinal cord of adult rats. Accumulation of [125I]NGF in lumbar dorsal root ganglia was monitored by gamma emission counting and radioautography. [125I]NGF, injected endoneurially in small quantities, was taken into sensory axons by a saturable process and was transported retrogradely to their cell bodies at a maximal rate of 2.5 to 7.5 mm/hr. Because very little [125I]NGF reached peripheral terminals, the results were interpreted to indicate that receptors for NGF are present on nonterminal segments of sensory axons. The specificity and high affinity of NGF uptake were illustrated by observations that negligible amounts of gamma activity accumulated in lumbar dorsal root ganglia after comparable intraneural injection of [125I] cytochrome C or [125I]oxidized NGF. Similar techniques were used to demonstrate avid internalization and retrograde transport of [125I]NGF by intraspinal axons arising from dorsal root ganglia. Following injection of [125I]NGF into lumbar or cervical regions of the spinal cord, neuronal perikarya were clearly labeled in radioautographs of lumbar dorsal root ganglia. Sites for NGF uptake on primary sensory neurons in the adult rat are not restricted to peripheral axon terminals but are extensively distributed along both peripheral and central axons. Receptors on axons provide a mechanism whereby NGF supplied by glia could influence neuronal maintenance or axonal regeneration.