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 neonatal chick cochlear nucleus, nucleus magnocellularis (NM), undergo cell death. Intracellular changes that precede the death of NM neurons include 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 by chloramphenicol, a mitochondrial protein synthesis inhibitor. This finding suggests that increased oxidative capacity is required for neuronal survival following loss of afferent input. To study changes in the ribosomes of afferent-deprived NM neurons, we obtained a monoclonal antibody to ribosomal RNA. This monoclonal antibody, Y10B, labels ribosomes 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 uniform 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 destined to die, based on their failure to synthesize protein, are unlabeled by the Y10B antibody. New gene expression is not necessary to initiate the change in ribosomal immunoreactivity that leads deafferented NM neurons toward cell death. Blocking cytoplasmic protein synthesis with cycloheximide had no effect on the biphasic change in Y10B labeling of afferent-deprived NM neurons. Treating chicks with chloramphenicol, however, prevented the recovery of Y10B immunoreactivity in NM neurons during the second phase of the response to afferent deprivation.