In our previous study, increases in Sox2 + cell number and glial proliferation were observed in the auditory nerve of the adult mouse cochlea shortly after ouabain exposure 22. Although it has been believed that severe adult astrocyte reactivity (or anisomorphic astrogliosis) has a significant negative impact on axonal regeneration, recent evidence suggests that astrocytes can act as stem/progenitor cells to promote adult nerve regeneration 18, 21. During these events, reactive astrocytes play an important role in promoting and modulating proper myelination or remyelination. Various phenotypical states of the astrocyte were identified during postnatal myelination and demyelination following homeostatic disturbance and injury in adult brain 19, 20. For example, NSPs in the SVZ and SGZ express several molecular markers associated with prototypic astrocytes, including Nestin, Gfap, S100β, the aldehyde dehydrogenase family, glulatamate transporters and excitatory amino acid transporter 1 and 2 16, 17, 18. Interestingly, recent studies have demonstrated that the majority of these NSPs have characteristics typical of glial cells 15. Brain injury and certain neurodegenerative disorders stimulate the proliferation of NSPs located in the SGZ and SVZ of the adult brain and the resulting proliferative neural cells migrate into damaged brain regions. NSPs have been characterized in several locations in the adult nervous system, including the subgranular zone (SGZ) of the dentate gyrus, the subventricular zone (SVZ) of the lateral ventricle and the spinal cord after injury 13, 14. It is essential to determine whether the self-renewing capability is still conserved in the endogenous cells of the adult auditory nerve. Previous studies showed that proliferative NSPs can be isolated from the auditory nerve of the perinatal cochlea 11, 12. However, evidence from studies of various animal models of neurodegenerative disease indicates that the temporal window for the successful transplantation of NSPs after nerve injury is very short and that long-term survival and integration of NSPs in the chronically injured host environment is limited 8, 9, 10. The transplantation of neural stem/progenitor cells (NSPs) to facilitate the regeneration of neural tissues offers a promising therapeutic strategy for treating a variety of neurodegenerative disorders, including SNHL 4, 5, 6, 7. It has been believed that loss of spiral ganglion neurons and auditory nerve fibers are irreversible in the adult ear without external intervention, resulting in permanent sensorineural hearing loss (SNHL). Damage to the auditory nerve and SGNs may occur not only secondarily to sensory hair cell loss, but also primarily in response to acoustic overexposure 3. Studies of human temporal bones have shown that one of the most common pathological changes observed in age-related hearing loss is the degeneration of SGNs 1, 2. 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.ĭegeneration of spiral ganglion neurons (SGNs) and their processes commonly occurs with aging, genetic mutations and cochlear injuries caused by noise or ototoxic drug exposure. ![]() Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. 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. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. ![]() It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain.
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