Journal of Neuroscience, Vol 14, 1994-2008, Copyright © 1994 by Society for Neuroscience
A biphasic change in ribosomal conformation during transneuronal degeneration is altered by inhibition of mitochondrial, but not cytoplasmic protein synthesis
GA Garden, KS Canady, DI Lurie, M Bothwell and EW Rubel
Virginia Merrill Bloedel Hearing Research Center, Department of Physiology, University of Washington School of Medicine, Seattle 98195.
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.
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