Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-11-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.139171 |
| _version_ | 1818242068426784768 |
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| author | Takahiro Wakizono Hideyuki Nakashima Tetsuro Yasui Teppei Noda Kei Aoyagi Kanako Okada Yasuhiro Yamada Takashi Nakagawa Kinichi Nakashima |
| author_facet | Takahiro Wakizono Hideyuki Nakashima Tetsuro Yasui Teppei Noda Kei Aoyagi Kanako Okada Yasuhiro Yamada Takashi Nakagawa Kinichi Nakashima |
| author_sort | Takahiro Wakizono |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T13:39:21Z |
| format | Article |
| id | doaj.art-b9e5695f8d1840c0afc707ee61da6105 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T13:39:21Z |
| publishDate | 2021-11-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-b9e5695f8d1840c0afc707ee61da61052022-12-22T00:22:51ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-11-01622Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regenerationTakahiro WakizonoHideyuki NakashimaTetsuro YasuiTeppei NodaKei AoyagiKanako OkadaYasuhiro YamadaTakashi NakagawaKinichi NakashimaSpiral 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.https://doi.org/10.1172/jci.insight.139171NeuroscienceStem cells |
| spellingShingle | Takahiro Wakizono Hideyuki Nakashima Tetsuro Yasui Teppei Noda Kei Aoyagi Kanako Okada Yasuhiro Yamada Takashi Nakagawa Kinichi Nakashima Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration JCI Insight Neuroscience Stem cells |
| title | Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration |
| title_full | Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration |
| title_fullStr | Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration |
| title_full_unstemmed | Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration |
| title_short | Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration |
| title_sort | growth factors with valproic acid restore injury impaired hearing by promoting neuronal regeneration |
| topic | Neuroscience Stem cells |
| url | https://doi.org/10.1172/jci.insight.139171 |
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