Abstract
Problem
Development of the auditory nerve is dependent on neurotrophic factors. Neurotrophins BDNF and NT-3 are critical in the later stages of development. More recently, a substance secreted by the early inner ear, otocyst-derived factor (ODF), was shown to stimulate development of primitive auditory neurons at the earliest stages. We hypothesized that this powerful neurotrophic substance might be capable of regenerating auditory neurons in the mature animal.
Methods
Cultured neurons and whole explants from neonatal mouse spiral ganglia were incubated with either BDNF or supernatant from an ODF-secreting cell line.
Results
Exposure to ODF resulted in large numbers of cells which stained with neuronal markers, and had neuronal morphology. Though they appeared somewhat different from the native spiral ganglion neurons seen in BDNF-treated cultures, they were present in vastly greater numbers, and appeared to arise from within the proliferating, migrating glial cell populations growing along with the neurons. These cells were not seen in cultures containing either control serum or BDNF. Addition of beta-bungarotoxin, a neurotoxin, to spiral ganglia just after harvest destroyed the native neurons, which did not regenerate upon addition of BDNF. However, many of the new neuron-like cells were observed after rescue with ODF, suggesting they represented a newly regenerated population of cells.
Conclusion
These data suggest that the components of ODF have the potential to regenerate neuronal cells, possibly from precursors or stem cells existing within the supporting cell populations of the auditory nerve.
Significance
The ability to regenerate auditory neurons would have exciting implications on the design and function of cochlear implants. Work continues in our lab to better define the properties of these new cells, and to isolate ODF's active component growth factors.
Support
Commonwealth of Pennsylvania's Tobacco Formula Fund.
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