Developing dorsal root ganglion neurons require trophic support from their central processes: evidence for a role of retrogradely transported nerve growth factor from the central nervous system to the periphery.

Abstract

Injury to the peripheral processes produces a profound cell loss (40-50%) in the dorsal root ganglion of newborn rats. Although division of central processes produces littie or no cellular change in sensory ganglion of adult animals, no Information has been available on the effect of dorsal root section in developing dorsal root ganglion. We show that 6 days after dorsal rhizotomy on newborn rats, there is a 50% decrease in neuronal number in L5 dorsal root ganglion. A combined central and peripheral lesion of the sensory process results in a greater decrease in neuronal number (70%). Both of these effects can be prevented by the concomitant treatment with nerve growth factor. We also demonstrate that 12'I-labeled nerve growth factor is retrogradely transported with high selectivity from the spinal cord to the dorsal root ganglion via the dorsal roots. The results indicate that trophic support for developing sensory neurons is provided through the central processes. This is presumably due to the uptake and retrograde transport of a trophic factor by the terminals of the central processes. The data suggest that nerve growth factor may be the trophic factor. (7) and the flow of axoplasm is slower than in the large peripherally directed axons (8, 9).Populations of developing neurons come under the influence of their peripheral fields and are able to make compensatory adjustments according to the sizes of the afferent input they receive (10-12) and the efferent output they project (13-16). The adjustments are made by way of corresponding alterations in cell number and size within the developing neuronal population. The sensory ganglion is unique in the sense that its target areas include both central neurons in the spinal cord and the innervated organs in the periphery. Despite the lack of morphological alteration reported after sectioning of the central process in adult animals, it is possible that developing DRG neurons receive trophic support from both central and peripheral target zones.Nerve growth factor (NGF) has long been thought to act as a trophic factor transferring information from the peripheral target organs to the innervating sympathetic and sensory neurons. Our recent findings (17) have demonstrated that eliminating the peripheral target influence by crushing the sciatic nerve in the newborn rat resulted in a substantial loss (40-50%) of neurons in L5 DRG. Treatment with NGF prevented the decrease in neuronal number of the axotomized DRG. In the present study, we examine the effects of central process axotomy on the survival of the neonatal neurons to evaluate the relative roles of central and peripheral contacts on the development of the DRG neurons and to determine if exogenous NGF can prevent the observed deleterious effects of central axonal injury.

The representation of peripheral nerve inputs in the S-I hindpaw cortex of rats raised with incompletely innervated hindpaws

“…This is consistent with reports of loss of sensory cell bodies in dorsal root ganglia after nerve injury in young mammals (Aldskogius and Risling, 198 1, 1983;Jorgensen and Dyck, 1979;Ranson, 1906;Risling et al, 1983;Yip and Johnson, 1984) and with the proposition that the patterns of cortical change after neonatal sciatic injury involve alterations in the capacity of the injured nerve to support normal development of the ascending hindpaw projection system.…”

“…For example, injury of hindlimb nerves in young animals results in loss of primary sensory neurons (Aldskogius and Risling, 198 1, 1983;Jorgensen and Dyck, 1979;Ranson, 1906;Risling et al, 1983;Yip and Johnson, 1984) and disorganization and shrinkage of the second-order nucleus gracilis (Johnson et al, 1972). Cellular barrels and segmented spatial patterns of axonal terminations like those seen in the S-I representation of the vibrissae have been shown in the S-I representation of the hindpaw in normal rats (Dawson and Killackey, 1984;Welker, 1976); interestingly, transection of the sciatic nerve on the day of birth in rats produces abnormal axonal termination patterns in the hindpaw cortex that resemble the disrupted patterns seen in the vibrissae cortex after injury ofthe infraorbital nerve (Dawson and Killackey, 1984).…”

Peripheral and Central Target Requirements for Survival of Embryonic Rat Dorsal Root Ganglion Neurons in Slice Cultures

“…Yip and Johnson (1984) found 50% cell loss in DRGs after dorsal rhizotomy in newborn rats, suggesting a dependence on factors from the spinal cord. However, when Himes and Tessler (1989) repeated this experiment, they found no cell loss.…”

The NGFI-B gene, a transcriptionally inducible member of the steroid receptor gene superfamily: genomic structure and expression in rat brain after seizure induction.

“…NGF appears to inhibit naturally occurring neuronal death (48) and to foster neuronal survival after axotomy (49). It can also induce chromaffin cells of the fetal adrenal medulla to differentiate into sympathetic neurons (1).…”