SYMPATHETIC NEURONS IN NEONATAL RATS REQUIRE ENDOGENOUS NEUROTROPHIN-3 FOR SURVIVAL

Gene deletion of neurotrophin-3 (NT3) results in severe sensory and sy mpathetic deficits that are incompatible with postnatal life in mice. We have now addressed the question of whether NT3 plays a role in the postnatal animal. An antiserum specific for NT3 and capable of blockin g the survival effect of the factor in vitro has been generated and gi ven to neonatal rats. Antiserum administration during either or both o f the first 2 postnatal weeks resulted in a 54-74% reduction in the si ze of the superior cervical ganglia, reflecting a loss of as many as 8 0% of all neurons, with a predominant effect on the neuropeptide Y con taining subpopulation. The immunoreactivities of NPY, tyrosine hydroxy lase, and p75 low affinity NGF receptor in nerve terminals within the mesenteric artery were also reduced, whereas that of the sensory neuro n neuropeptide, calcitonin gene related peptide was less affected. The se results demonstrate that the majority of sympathetic neurons of the neonatal rat are dependent on endogenous NT3 for their survival at a time when they are also dependent on another survival factor, NGF, thu s apparently providing a clear example of a population of neurons requ iring for their survival the simultaneous supply of more than one trop hic factor.