ENDOGENOUS NERVE GROWTH-FACTOR AND NEUROTROPHIN-3 ACT SIMULTANEOUSLY TO ENSURE THE SURVIVAL OF POSTNATAL SYMPATHETIC NEURONS IN-VIVO

For many years nerve growth factor was the only factor known to influe nce embryonic and postnatal development of sympathetic neurons. Its de privation by antibody neutralization or gene mutation results in exten sive neuron death. Recently it has been shown that these neurons also require neurotrophin-3 for survival in the late developmental period. Using neurotrophin-3 antiserum to neutralize endogenous factor in newb orn rats, our laboratory has shown that extensive numbers of neurons a re lost from both pre-and paravertebral ganglia, indicating a continui ng requirement for neurotrophin-3. In the present study we sought to d etermine whether neurons could survive in vivo in the presence of exce ss amounts of either nerve growth factor or neurotrophin-3 alone. Cons istent with previous findings, administration of antiserum to nerve gr owth factor or neurotrophin-3 to newborn rats for eight days, resulted in an extensive loss of sympathetic neurons. Interestingly, administr ation of neurotrophin-3 together with nerve growth factor antiserum or nerve growth factor with neurotrophin-3 antiserum, reversed this neur onal loss. However the latter combination was less effective than the former. Furthermore, the ability of exogenous nerve growth factor to i ncrease both the number and size of sympathetic neurons was prevented by the simultaneous deprivation of endogenous neurotrophin-3. Unlike n erve growth factor, exogenous neurotrophin-3 failed to rescue the natu rally occurring neuronal death in these newborn rats. Further evidence for a physiological role for both nerve growth factor and neurotrophi n-3 was found by the detection of both trkA and trkC immunoreactivity in neurons of the superior cervical ganglion. Taken together, these re sults suggest that sympathetic neurons do not have an absolute require ment for either nerve growth factor or neurotrophin-3 and that the end ogenous supply of either factor alone is insufficient to support neuro nal survival postnatally. However, while each factor may play similar roles in the regulation of postmitotic neuronal function, some evidenc e for distinct functions has been identified. (C) 1997 Published by El sevier Science Ltd.