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Increased ototoxicity in both young and old mice
Abstract:
Preweanling, postadolescent, and post-middle-aged CBA/J mice received injections of kanamycin sulfate for two weeks, followed by electrocochleographic (isoelectric auditory nerve-evoked potential thresholds from 2,000 to 64,000 Hz) and histocochleographic (hair cell counts from cochlea whole-mount preparations) analysis. The preweanling mice had structural and functional losses from all portions of the cochlea, while the postadolescent mice had no structural and minimal functional loss. The oldest mice had basal inner and outer hair cell loss and elevated high frequency thresholds. This is an experimental validation of the clinical observation that infants are most susceptible to aminoglycosidic ototoxicity. It also support the suspicion that older persons are also susceptible to ototoxicity and provides the first animal model for experimentally investigating these age-dependent effects.
Insights
Infants are most susceptible to kanamycin ototoxicity, experiencing cochlear damage. Older mice also showed age-dependent hearing loss and hair cell damage, validating clinical observations.
Area of Science:
- Ototoxicology
- Auditory Neuroscience
- Pharmacology
Background:
- Aminoglycoside antibiotics, like kanamycin, are known to cause ototoxicity.
- Age-related susceptibility to ototoxicity is clinically observed but poorly understood at the molecular and cellular levels.
Purpose of the Study:
- To experimentally validate the age-dependent ototoxicity of kanamycin sulfate in mice.
- To establish an animal model for investigating the mechanisms of aminoglycoside-induced hearing loss across different age groups.
Main Methods:
- CBA/J mice of three age groups (preweanling, postadolescent, post-middle-aged) received kanamycin sulfate for two weeks.
- Functional assessment using electrocochleography to measure auditory nerve-evoked potential thresholds.
- Structural assessment via histocochleography to quantify hair cell loss in cochlea whole-mount preparations.
Main Results:
- Preweanling mice exhibited significant structural and functional cochlear losses across all regions.
- Postadolescent mice showed minimal functional loss and no structural damage.
- Older mice displayed basal hair cell loss and elevated high-frequency hearing thresholds.
Conclusions:
- Kanamycin sulfate ototoxicity is most severe in the youngest mice, supporting clinical observations in infants.
- Older mice demonstrate age-dependent susceptibility to kanamycin-induced hearing impairment and hair cell damage.
- This study provides a novel animal model for exploring age-related differences in aminoglycoside ototoxicity.