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

Authors :
Teppei Noda
Kei Aoyagi
Takashi Nakagawa
Tetsuro Yasui
Kinichi Nakashima
Takahiro Wakizono
Kanako Okada
Hideyuki Nakashima
Yasuhiro Yamada
Source :
JCI Insight
Publication Year :
2021
Publisher :
American Society for Clinical Investigation, 2021.

Abstract

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.

Details

ISSN :
23793708
Volume :
6
Database :
OpenAIRE
Journal :
JCI Insight
Accession number :
edsair.doi.dedup.....279ef93d855bde92d43021b250dc7e9a