Abstract
The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration.
Highlights
Of neural stem/progenitor cells (NSPs) located in the SGZ and SVZ of the adult brain, and the resulting proliferative neural cells migrate into damaged brain regions
Cell counts indicated that the density of Sox10+ glial cells increased significantly in ouabain-treated auditory nerves at 3 and 7 days after ouabain exposure (ANOVA, p < 0 .05; Fig. 1f), increasing from approximately 40% in adult controls to 70% in injured samples (Fig. 1g)
Transcriptomic analysis of ouabain-exposed auditory nerves showed that acute injury caused up-regulation of numerous genes that are associated with neurogenesis and which are normally elevated during the early stages of postnatal auditory nerve development
Summary
Of NSPs located in the SGZ and SVZ of the adult brain, and the resulting proliferative neural cells migrate into damaged brain regions. Various phenotypical states of the astrocyte were identified during postnatal myelination and demyelination following homeostatic disturbance and injury in adult brain[19,20]. During these events, reactive astrocytes play an important role in promoting and modulating proper myelination or remyelination. Increases in Sox2+ cell number and glial proliferation were observed in the auditory nerve of the adult mouse cochlea shortly after ouabain exposure[22]. We report characterization of the cellular and molecular alterations occurring in ouabain-treated ears and examined the regenerative capability of adult auditory nerves in response to SGN death with a focus on glial cells
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