The effects of nerve growth factor and its antiserum on the postnatal development and survival after injury of sensory neurons in rat dorsal root ganglia

Abstract

Nerve growth factor (NGF) is known to be essential for survival and maintenance of sympathetic ganglia and of embryonic sensory ganglia of neural crest origin. The present study examined the physiological and pharmacological roles of NGF in the postnatal development of sensory neurons in the dorsal root ganglion (DRG). In contrast to what is generally stated in the literature, administration of NGF antiserum to newborn rats for a period of 7 days resulted in a significant (~20%) reduction of neuronal number in the lumbar DRG. Size spectrum analysis of surviving neurons revealed a shift toward larger sizes, presumably due to a preferential loss of small cells. The number of neurons in the L5 DRG was studied at various times after unilateral sciatic nerve crush in 1-day-old rats. Axotomy resulted in a substantial loss (40 to 50%) of neurons in the immature DRG. Administration of NGF antiserum to animals with axotomized DRG did not increase cell death when compared with the axotomized controls. However, the number of neurons in the antiserum-treated ganglia decreased by the same percentage (20%) when compared with the control serum-treated ganglia before and after axotomy. Treatment with NGF initially prevented the loss of neurons in the axotomized DRG. However, some neurons died during the first week despite continued NGF administration; and, subsequent to NGF withdrawal, neuronal number decreased to the same level as in control animals. Thus, removal of exogenous NGF resulted in the death of the sensory neurons which had been maintained. These results indicate that cells no longer physiologically dependent on NGF for survival (as indicated by lack of cell death in the presence of NGF antiserum in the axotomized DRG) can be sustained by pharmacological administration of NGF.