Influence of mitochondrial protein synthesis inhibition on deafferentation-induced ultrastructural changes in nucleus magnocellularis of developing chicks.

Following cochlea removal in developing chicks, about 30% of the neurons in the ipsilateral second-order auditory nucleus, nucleus magnocellularis, undergo cell death. Administration of chloramphenicol, a mitochondrial protein synthesis inhibitor, results in a pronounced increase in deafferentation-induced cell death. In this study, we examined whether the chloramphenicol enhancement of deafferentation-induced cell death reveals the same ultrastructural characteristics that are seen in degenerating nucleus magnocellularis neurons after cochlea removal alone. Unilateral cochlea removal was performed on anaesthetized posthatch chicks. One group of animals was simultaneously treated with chloramphenicol. Six, twelve, or twenty-four hours following cochlea removal, n. magnocellularis neurons were studied by routine transmission electron microscopy. Particular attention was paid to the integrity of the polyribosomes and rough endoplasmic reticulum. Two ultrastructurally different types of neuronal degeneration were observed in the deafferented nucleus magnocellularis neurons: an early onset electron-lucent type that always involved ribosomal dissociation and a late-onset electron-dense type displaying nuclear pyknosis and severely damaged mitochondria. The percentage of nucleus magnocellularis neurons displaying ribosomal disintegration following cochlea removal was found to be markedly increased after chloramphenicol treatment. This finding suggests that mitochondrial function is important for the maintenance of a functional protein synthesis apparatus following deafferentation.