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Nox3-Derived Superoxide in Cochleae Induces Sensorineural Hearing Loss
- Source :
- The Journal of Neuroscience
- Publication Year :
- 2021
- Publisher :
- Society for Neuroscience, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 15292401
- Volume :
- 41
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....229a062cf7cee3f3469f265fda6aa55a