Growth factors with valproic acid restore injury-impaired hearing by promoting neuronal regeneration
| Autor: | Teppei Noda, Kei Aoyagi, Takashi Nakagawa, Tetsuro Yasui, Kinichi Nakashima, Takahiro Wakizono, Kanako Okada, Hideyuki Nakashima, Yasuhiro Yamada |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Hearing loss
SOX10 Stem cells Mice SOX2 otorhinolaryngologic diseases medicine Animals Humans Regeneration Inner ear Neuronal stem cells Hearing Loss Spiral ganglion Neurons Adult stem cells business.industry Valproic Acid General Medicine medicine.disease medicine.anatomical_structure Resource and Technical Advance Sensorineural hearing loss sense organs medicine.symptom Stem cell business Neuroscience Adult stem cell |
| Zdroj: | JCI Insight |
| ISSN: | 2379-3708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|