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Publication : Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration.

First Author  Wakizono T Year  2021
Journal  JCI Insight Volume  6
Issue  22 PubMed ID  34806649
Mgi Jnum  J:353698 Mgi Id  MGI:6836427
Doi  10.1172/jci.insight.139171 Citation  Wakizono T, et al. (2021) Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration. JCI Insight 6(22):e139171
abstractText  Spiral ganglion neurons (SGNs) are primary auditory neurons in the spiral ganglion that transmit sound information from the inner ear to the brain and play an important role in hearing. Impairment of SGNs causes sensorineural hearing loss (SNHL), and it has been thought until now that SGNs cannot be regenerated once lost. Furthermore, no fundamental therapeutic strategy for SNHL has been established other than inserting devices such as hearing aids and cochlear implants. Here we show that the mouse spiral ganglion contains cells that are able to proliferate and indeed differentiate into neurons in response to injury. We suggest that SRY-box transcription factor 2/SRY-box transcription factor 10-double-positive (Sox2/Sox10-double-positive) Schwann cells sequentially started to proliferate, lost Sox10 expression, and became neurons, although the number of new neurons generated spontaneously was very small. To increase the abundance of new neurons, we treated mice with 2 growth factors in combination with valproic acid, which is known to promote neuronal differentiation and survival. This treatment resulted in a dramatic increase in the number of SGNs, accompanied by a partial recovery of the hearing loss induced by injury. Taken together, our findings offer a step toward developing strategies for treatment of SNHL.
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