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Published on: October 11, 2024
Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma
Safa Alqudah1,2, Mark Chertoff1, Dianne Durham3
1Department of Hearing and Speech, School of Health Professions, University of Kansas Medical Center, Kansas City, Kansas, USA.
Abstract:
Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice. MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting that MsrA is part of a mechanism that protects the cochlea from acoustic damage. MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNA MsrB1 was compromised at 6 months old, but not in younger MsrA knockout mice (compared to controls). The identification of MsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy.
Insights
Methionine sulfoxide reductase A (MsrA) protects hearing from oxidative damage and noise-induced injury. MsrA knockout mice exhibit progressive hearing loss and heightened noise sensitivity, indicating MsrA
Area of Science:
- Otoacoustic emissions
- Neuroscience
- Molecular biology
Background:
- Methionine sulfoxide reductases (MsrA and MsrB) are crucial for protein protection against oxidative damage.
- These enzymes play a role in mitigating the pathological effects of neurodegenerative diseases.
- Understanding MsrA's function in the auditory system is important for hearing health.
Purpose of the Study:
- To investigate the auditory phenotype of MsrA knockout mice.
- To determine the role of MsrA in protecting the cochlea from acoustic damage and noise exposure.
- To explore the expression patterns of MsrA and MsrB in the cochlea.
Main Methods:
- Characterization of auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) in MsrA knockout and wild-type mice.
- Assessment of noise sensitivity at different ages.
- Quantitative analysis of MsrA and MsrB1 mRNA expression in cochlear tissues following acoustic stimulation.
Main Results:
- MsrA knockout mice displayed elevated high-frequency hearing thresholds and reduced DPOAE levels compared to controls.
- Hearing deficits progressively worsened with age in MsrA knockout mice.
- Increased MsrA mRNA levels were observed in the cochlea after acoustic stimulation, and MsrB1 mRNA expression was reduced in older MsrA knockout mice.
Conclusions:
- MsrA is identified as a protective factor in the cochlea against early-onset hearing loss and acoustic trauma.
- MsrA plays a role in mitigating noise-induced cochlear damage.
- Further research into Msr-based therapies could offer strategies for preventing noise exposure-related hearing damage.
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