Comparative dynamics of retrograde transport of nerve growth factor and horseradish peroxidase in rat lumbar dorsal root ganglia

Abstract

The dynamics of the retrograde transport of [125I] nerve growth factor (NGF) and horseradish peroxidase (HRP) in dorsal root ganglion (DRG) neurons were studied in rats. After injection of [125I]NGF or HRP into crushed sciatic nerve, labelling was examined in spinal nerves, dorsal root ganglia, dorsal roots and spinal cord. Retrograde transport of either [125I]NGF or HRP was first observed in DRG neurons 6 h after injection: The maximal rate of transport (7 mm h-1) was similar for both proteins. Significant differences in the sizes of DRG neurons labelled by [125I]NGF were observed and were dependent upon survival time. No such difference was seen in HRP-injected animals. At 6 h after injection, 60% of all the HRP-labelled cells had a diameter of more than 25 micron, whereas 90% of all the [125I]NGF-labelled neurons had a diameter of less than 25 micron. With increasing survival times there was a gradual shift in the size of [125I]NGF-labelled neurons towards larger diameters. Thus, 24 h after the [125I]NGF injection, 83% of the labelled cells had a diameter greater than 25 micron. The data suggest that small diameter neurons retrogradely transport and turnover NGF faster than larger diameter neurons. There was a preferential accumulation of silver grains in small DRG neurons (mean diameter 25 micron) at early survival times (4 and 8 h); at the later survival time (24 h) the reverse was observed, i.e. larger neurons (mean diameter 42 micron) were labelled. In contrast, the mean diameter of HRP-labelled neurons remained constant (30 micron) at all times after injection. The total number of neurons ultimately labelled (approximately 80-85%) appeared to be the same with both tracers. In addition, the lack of transganglionic transport of NGF into the spinal cord and the short time span of the observable accumulated radioactivity in DRG neurons suggest the rate of degradation of transported NGF seems to be faster than HRP. As a practical matter, these data indicate that observing cells within DRG which accumulate retrogradely transported [125I]NGF at any one time gives an inaccurate picture of the size properties of cells capable of transporting the ligand.