TY - JOUR
T1 - Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration
AU - Wakizono, Takahiro
AU - Nakashima, Hideyuki
AU - Yasui, Tetsuro
AU - Noda, Teppei
AU - Aoyagi, Kei
AU - Okada, Kanako
AU - Yamada, Yasuhiro
AU - Nakagawa, Takashi
AU - Nakashima, Kinichi
N1 - Funding Information:
We appreciate the technical assistance from the Research Support Center, Kyushu University Graduate School of Medical Sciences. We thank T. Matsuda, S. Katada, and T. Imamura for discussion; Y. Nakaga-wa for excellent secretarial assistance; I. Smith for proofreading the manuscript; A. Dabdoub for providing valuable comments on the manuscript; and M. Ozawa for supporting generation of the transgenic mice. This study was supported by grants from the Sasakawa Scientific Research Grant to TY, a Grant-in-Aid for Young Scientists (B) (17K16925) to T. Noda, and a Grant-in-Aid for Scientific Research on Innovative Areas (16H06527) and (16K21734) to KN.
Funding Information:
We appreciate the technical assistance from the Research Support Center, Kyushu University Graduate School of Medical Sciences. We thank T. Matsuda, S. Katada, and T. Imamura for discussion; Y. Nakagawa for excellent secretarial assistance; I. Smith for proofreading the manuscript; A. Dabdoub for providing valuable comments on the manuscript; and M. Ozawa for supporting generation of the transgenic mice. This study was supported by grants from the Sasakawa Scientific Research Grant to TY, a Grant-in-Aid for Young Scientists (B) (17K16925) to T. Noda, and a Grant-in-Aid for Scientific Research on Innovative Areas (16H06527) and (16K21734) to KN.
Publisher Copyright:
Copyright: © 2021, Wakizono et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2021/11/22
Y1 - 2021/11/22
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85120382644&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.139171
DO - 10.1172/jci.insight.139171
M3 - Article
C2 - 34806649
AN - SCOPUS:85120382644
VL - 6
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 22
M1 - e139171
ER -
