ULTRASTRUCTURAL-CHANGES OF SYMPATHETIC NEURONS FOLLOWING NEUROTROPHIN-3 ANTISERUM TREATMENT IN YOUNG-RAT

We have previously demonstrated that neurotrophin-3 antiserum administ ration to rats during the first 2 postnatal weeks results in a massive reduction of neurons in the superior cervical ganglion. In the presen t study, an ultrastructural analysis was undertaken to elucidate the m echanism by which neurotrophin-3 deprivation causes neuronal death. Ne wborn and 4-week-old rats were injected with either neurotrophin-3 ant iserum or normal rabbit serum or used without injection. Superior cerv ical ganglia from each animal were examined by routine electron micros copy. Most neurons in the ganglia from untreated rats had a large and round nucleus with one or two nucleoli. Chromatin within the nucleus w as evenly distributed. A double-layer nuclear membrane could be distin guished and the cytoplasm contained abundant organelles. Treatment wit h neurotrophin-3 antiserum for 24 h in neonates resulted in chromatin clumping in the nucleus of many neurons. The nuclear membrane became r ough and occasionally folded. In the cytoplasm, the Golgi apparatus wa s disrupted. Three days after treatment, these changes became more obv ious. The chromatin in the nucleus was often aggregated and marginaliz ed. Vacuolation was present in many membranous organelles throughout t he cytoplasm. Although neurotrophin-3 antiserum given to 4-week-old ra ts had little effect on overall neuronal numbers (Tafreshi, Zhou, and Rush, unpublished), a few neurons, undergoing either apoptotic or cyto lytic cell death, were identified 7 days later. Most affected neurons were located near small blood vessels or capillaries and were associat ed with numerous nonneuronal cells. The debris of degenerating neurons were surrounded by the processes of glia cells. These findings suppor t the view that loss of endogenous neurotrophin-3 following neutraliza tion with specific antibody leads to activation of apoptotic pathways within the affected neurons. However, the presence of neurons dying as a result of cytolysis suggests that other mechanisms may also be invo lved. (C) 1997 Academic Press.