A BIPHASIC CHANGE IN RIBOSOMAL CONFORMATION DURING TRANSNEURONAL DEGENERATION IS ALTERED BY INHIBITION OF MITOCHONDRIAL, BUT NOT CYTOPLASMIC PROTEIN-SYNTHESIS

Following loss of eighth nerve input, 20-40% of neurons in the neonata l chick cochlear nucleus, nucleus magnocellularis (NM), undergo cell d eath. Intracellular changes that precede the death of NM neurons inclu de increased oxidative metabolism and mitochondrial volume, decreased cytoplasmic protein synthesis, and destruction of ribosomes. Six hours following afferent deprivation, dying NM neurons demonstrate complete loss of ribosomes and cessation of protein synthesis, suggesting that the rapid destruction of ribosomes leads to neuronal death. Increased NM neuron death occurs when mitochondrial upregulation is prevented b y chloramphenicol, a mitochondrial protein synthesis inhibitor. This f inding suggests that increased oxidative capacity is required for neur onal survival following loss of afferent input. To study changes in th e ribosomes of afferent-deprived NM neurons, we obtained a monoclonal antibody to ribosomal RNA. This monoclonal antibody, Y10B, labels ribo somes of all NM neurons receiving normal synaptic activity. Following removal of afferent input, NM neurons demonstrate a biphasic change in their pattern of Y10B label. During the initial phase, there is a uni form decrease in the density of Y10B label. In the second phase, some NM neurons recover the capacity to bind the Y10B antibody while others remain unlabeled. During this second phase, NM neurons putatively des tined to die, based on their failure to synthesize protein, are unlabe led by the Y10B antibody. New gene expression is not necessary to init iate the change in ribosomal immunoreactivity that leads deafferented NM neurons toward cell death. Blocking cytoplasmic protein synthesis w ith cycloheximide had no effect on the biphasic change in Y10B labelin g of afferent-deprived NM neurons. Treating chicks with chloramphenico l, however, prevented the recovery of Y10B immunoreactivity in NM neur ons during the second phase of the response to afferent deprivation.