Nox3-Derived Superoxide in Cochleae Induces Sensorineural Hearing Loss
| Autor: | Shigeru Hirano, Hiroaki Mohri, Hirofumi Sakaguchi, Yuzuru Ninoyu, Naoaki Saito, Takehiko Ueyama |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Aging Cell type Hearing loss Hearing Loss Sensorineural Cre recombinase Biology Mice 03 medical and health sciences 0302 clinical medicine drug-induced hearing loss Superoxides Neurobiology of Disease otorhinolaryngologic diseases medicine Animals Inner ear Gene Knock-In Techniques Research Articles Spiral ganglion Cochlea hearing loss reactive oxygen species NADPH oxidase General Neuroscience NADPH Oxidases medicine.disease Cell biology Mice Inbred C57BL noise-induced hearing loss age-related hearing loss 030104 developmental biology medicine.anatomical_structure Hearing Loss Noise-Induced Female Sensorineural hearing loss sense organs Cisplatin medicine.symptom Noise 030217 neurology & neurosurgery Noise-induced hearing loss |
| Zdroj: | The Journal of Neuroscience |
| ISSN: | 1529-2401 |
| Popis: | Reactive oxygen species (ROS) produced by NADPH oxidases (Nox) contribute to the development of different types of sensorineural hearing loss (SNHL), a common impairment in humans with no established treatment. Although the essential role of Nox3 in otoconia biosynthesis and its possible involvement in hearing have been reported in rodents, immunohistological methods targeted at detecting Nox3 expression in inner ear cells reveal ambiguous results. Therefore, the mechanism underlying Nox3-dependent SNHL remains unclear and warrants further investigation. We generatedNox3-Creknock-in mice, in which Nox3 was replaced withCre recombinase(Cre). UsingNox3-Cre;tdTomatomice of either sex, in which tdTomato is expressed under the control of theNox3promoter, we determined Nox3-expressing regions and cell types in the inner ear. Nox3-expressing cells in the cochlea included various types of supporting cells, outer hair cells, inner hair cells, and spiral ganglion neurons. Nox3 expression increased with cisplatin, age, and noise insults. Moreover, increased Nox3 expression in supporting cells and outer hair cells, especially at the basal turn of the cochlea, played essential roles in ROS-related SNHL. The extent of Nox3 involvement in SNHL follows the following order: cisplatin-induced hearing loss > age-related hearing loss > noise-induced hearing loss. Here, on the basis ofNox3-Cre;tdTomato, which can be used as a reporter system (Nox3-Cre+/−;tdTomato+/+andNox3-Cre+/+;tdTomato+/+), andNox3-KO (Nox3-Cre+/+;tdTomato+/+) mice, we demonstrate that Nox3 inhibition in the cochlea is a promising strategy for ROS-related SNHL, such as cisplatin-induced HL, age-related HL, and noise-induced HL.SIGNIFICANCE STATEMENTWe found Nox3-expressing regions and cell types in the inner ear, especially in the cochlea, usingNox3-Cre;tdTomatomice, a reporter system generated in this study. Nox3 expression increased with cisplatin, age, and noise insults in specific cell types in the cochlea and resulted in the loss (apoptosis) of outer hair cells. Thus, Nox3 might serve as a molecular target for the development of therapeutics for sensorineural hearing loss, particularly cisplatin-induced, age-related, and noise-induced hearing loss. |
| Databáze: | OpenAIRE |
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