Rats and guinea pigs, when immunized with mouse nerve growth factor, produce antibodies that cross-react with their own nerve growth factor. The antibodies reach developing offspring of these animals both prenatally (rats and guinea pigs) and postnatally (rats). Depriving the fetus of nerve growth factor in this way results in the destruction of up to 85 percent of dorsal root ganglion neurons as well as destruction of sympathetic neurons. Sensory neurons of placodal origin in the nodose ganglion were not affected. These data demonstrate that dorsal root ganglion neurons go through a phase of nerve growth factor dependence in vivo.

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An experimental autoimmune model of nerve growth factor (NGF) deprivation has been used to assess the role of NGF in the development of various cell types in the nervous system. Adult rats immunized with 2.5S mouse NGF in complete Freund's adjuvant produced antibodies that crossreacted with their own NGF and that were transferred in utero to the fetus and in milk to the neonate. Cross-fostering experiments were carried out to separate the effects of exposure to anti-NGF in utero from those due to exposure through the milk. Anti-NGF transferred in utero and in milk resulted in the destruction of peripheral sympathetic neurons assessed by morphological methods (light microscopy) and biochemical methods (tyrosine hydroxylase activity, choline acetyltransferase activity, and protein content). No effects were observed on the adrenal medulla. Offspring of NGF-immunized females exposed to anti-NGF in utero had a decreased protein content in the dorsal root ganglia and were unable to transport 125I-labeled NGF injected in the forepaw to the dorsal root ganglia. These results suggest that a subpopulation of sensory neurons is dependent on NGF for survival during some period of fetal development. This model offers the potential for determining the degree and time of dependence of various cell types on NGF. Nerve growth factor (NGF) is a protein that acts on peripheral neurons of neural crest origin in both avian and mammalian species (1). Much evidence suggests that NGF is a retrogradely transported trophic factor that regulates the development of immature sympathetic peripheral neurons and the maintenance of mature sympathetic neurons (2-4). Very little is known about the role of NGF for mammalian sensory neurons, although it has been shown that rat dorsal root ganglion (DRG) neurons retain the capability of retrograde axonal transport of NGF throughout postnatal development (5).One means of assessing the physiological role of NGF on the diverse neuronal populations of the developing mammalian nervous system is to deprive cells of NGF. Because the normal source of NGF is not known, and specific NGF antagonists are not available, the only mechanism of producing a systemic deprivation of NGF is immunological. Previous studies (6)(7)(8) have demonstrated that antibodies to NGF can be prepared by repeated injections of animals with NGF derived from mouse. These and subsequent studies, using anti-NGF serum, demonstrated that mammalian sympathetic neurons of the paraand prevertebral ganglia die if deprived of NGF during the neonatal period. Other neural cell types (the short adrenergic neurons innervating the urogenital tract and brown adipose tissue, adrenal medullary chromaffin cells, peripheral sensory neurons of the DRG, and central adrenergic neurons) are not destroyed by anti-NGF serum administered in the neonatal period (9, 10).The usefulness of antiserum-induced NGF deprivation is limited by problems associated with its repeated administration-e.g., serum sickness. An an alternative approach, we have developed ...

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