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Updated: Apr 12, 2026
Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage
Published on: February 10, 2023
Attenuation of hearing loss in DBA/2J mice by anti-apoptotic treatment
Linlin Yang1, Heng Zhang2, Xu Han2
1Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, Shandong, PR China; Department of Otorhinolaryngology-Head and Neck Surgery, Yuhuangding Hospital, 20 East Yuhuangding Road, Yantai 264000, Shandong, PR China.
Abstract:
DBA/2J mice are characterized by early onset hearing loss at about 3-4 weeks of age. Mutations in cadherin 23 (Cdh23) and fascin-2 (Fscn2) are responsible for the phenotypes, but the underlying mechanism is unknown. In the present study, DBA/2J mice displayed progressive hair cell loss and degeneration of spiral ganglion neurons (SGNs) after 2 weeks of age; however, the mRNA level of Caspase-3 in the inner ears was much higher at 2 weeks of age than that at 4 or 8 weeks of age. Moreover, transcriptional levels of Caspase-3 and Caspase-9 in the inner ears of DBA/2J mice were significantly higher than those of C57BL/6J mice at 2 or 8 weeks of age. Immunohistochemistry localized Caspase-3 and Caspase-9 mainly to the hair cells, SGNs and stria vascularis of the cochleae. To determine the significance of caspase-dependent apoptosis in the hearing loss, the pan-caspase inhibitor Z-VAD-FMK was given intraperitoneally to DBA/J2 mice over an 8-week period starting at one week of age. Blockage of caspases preserved hearing in the mice by more than 10 dB (dB) sound pressure level (SPL) of the ABR thresholds and significantly reduced outer hair cell loss at the basal turns of the cochleae. These results demonstrate that apoptosis in the cochleae of DBA/J2 mice contributes to the early onset of hearing loss, which can be attenuated by anti-apoptotic treatment.
Insights
Early-onset hearing loss in DBA/2J mice is linked to apoptosis. Blocking caspases significantly preserved hearing and reduced hair cell loss, indicating apoptosis contributes to this condition.
Area of Science:
- Ototolaryngology
- Neuroscience
- Genetics
Background:
- DBA/2J mice exhibit early-onset hearing loss by 3-4 weeks of age.
- While cadherin 23 (Cdh23) and fascin-2 (Fscn2) mutations are implicated, the mechanism of hearing loss in DBA/2J mice remains unclear.
- Progressive hair cell loss and spiral ganglion neuron (SGN) degeneration occur after 2 weeks of age in DBA/2J mice.
Purpose of the Study:
- To investigate the role of caspase-dependent apoptosis in the early-onset hearing loss of DBA/2J mice.
- To determine if inhibiting caspases can attenuate hearing loss and cochlear degeneration.
Main Methods:
- Compared mRNA levels of Caspase-3 and Caspase-9 in DBA/2J and C57BL/6J mice inner ears at different ages.
- Utilized immunohistochemistry to localize Caspase-3 and Caspase-9 expression in cochlear tissues.
- Administered the pan-caspase inhibitor Z-VAD-FMK to DBA/2J mice from one week of age for 8 weeks.
- Assessed auditory brainstem response (ABR) thresholds and quantified outer hair cell loss.
Main Results:
- DBA/2J mice showed significantly higher Caspase-3 and Caspase-9 mRNA levels compared to controls, particularly at 2 weeks of age.
- Caspase-3 and Caspase-9 were localized to hair cells, SGNs, and stria vascularis.
- Z-VAD-FMK treatment preserved hearing by over 10 dB SPL in ABR thresholds and reduced outer hair cell loss.
- Apoptosis was confirmed to be a significant contributor to cochlear degeneration.
Conclusions:
- Apoptosis in the cochlea plays a critical role in the early-onset hearing loss observed in DBA/2J mice.
- Inhibition of caspases offers a potential therapeutic strategy to attenuate hearing loss and protect cochlear structures.
- Targeting apoptotic pathways may be a viable approach for treating certain forms of hearing impairment.
