Back to Search
Start Over
The DNA methylation inhibitor RG108 protects against noise-induced hearing loss
- Source :
- Cell Biology and Toxicology
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Background Noise-induced hearing loss represents a commonly diagnosed type of hearing disability, severely impacting the quality of life of individuals. The current work is aimed at assessing the effects of DNA methylation on noise-induced hearing loss. Methods Blocking DNA methyltransferase 1 (DNMT1) activity with a selective inhibitor RG108 or silencing DNMT1 with siRNA was used in this study. Auditory brainstem responses were measured at baseline and 2 days after trauma in mice to assess auditory functions. Whole-mount immunofluorescent staining and confocal microcopy of mouse inner ear specimens were performed to analyze noise-induced damage in cochleae and the auditory nerve at 2 days after noise exposure. Results The results showed that noise exposure caused threshold elevation of auditory brainstem responses and cochlear hair cell loss. Whole-mount cochlea staining revealed a reduction in the density of auditory ribbon synapses between inner hair cells and spiral ganglion neurons. Inhibition of DNA methyltransferase activity via a non-nucleoside specific pharmacological inhibitor, RG108, or silencing of DNA methyltransferase-1 with siRNA significantly attenuated ABR threshold elevation, hair cell damage, and the loss of auditory synapses. Conclusions This study suggests that inhibition of DNMT1 ameliorates noise-induced hearing loss and indicates that DNMT1 may be a promising therapeutic target. Graphical abstract
- Subjects :
- 0301 basic medicine
Hearing loss
Health, Toxicology and Mutagenesis
Phthalimides
Hair cells
Toxicology
Mice
03 medical and health sciences
0302 clinical medicine
otorhinolaryngologic diseases
medicine
Animals
Inner ear
Cochlea
Spiral ganglion
DNA methylation
business.industry
Tryptophan
Auditory Threshold
Cell Biology
medicine.disease
Cell biology
030104 developmental biology
medicine.anatomical_structure
Hearing Loss, Noise-Induced
Quality of Life
DNMT1
Original Article
sense organs
Hair cell
Noise-induced hearing loss
medicine.symptom
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15736822 and 07422091
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Cell Biology and Toxicology
- Accession number :
- edsair.doi.dedup.....1facc6777dfcac08c7c5d79516fbfdb8