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Published on: November 26, 2015
Dynamic distribution of ototoxic gentamicin entry into inner hair cells of mice
Ke Liu1, Chuang Shi, Yuhan Sun
1Department of Otolaryngology, Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital , Beijing.
Conclusion:
Dynamic distribution of ototoxic gentamicin entry into inner hair cells (IHCs) may cause an interruption of cochlear ribbon synapse.
Objective:
To explore the pattern of uptake of gentamicin into IHCs, as well as its possible contribution to hearing loss.
Methods:
Adult C57 mice were injected intraperitoneally with gentamicin (100 mg/kg, conjugated with Texas Red ester) continuously for 14 days. The hearing thresholds were detected by auditory brainstem response (ABR) examinations. Immunostaining and confocal microscopy were utilized to trace gentamicin distribution, as well as the expression of RIBEYE/CtBP2 in mouse IHCs. Scanning electron microscopy (SEM) observation was used to find possible alterations of stereocilia.
Results:
The distribution of gentamicin in IHCs was first found on the 4th day and the accumulation of gentamicin was increased significantly on the 7th day after treatment, corresponding to the maximal elevation of the hearing threshold. However, the accumulation of gentamicin on the 14th day did not show significant differences compared with the level found on the 7th day. In addition, the uptake of gentamicin was excessively identified at or near the synaptic ribbons of IHCs throughout the 4th, 7th, and 14th days after the treatment, suggesting that cochlear ribbon synapses could be affected by ototoxic gentamicin exposure.
Insights
Ototoxic gentamicin accumulates in inner hair cells (IHCs), potentially disrupting cochlear ribbon synapses and contributing to hearing loss. This study tracks gentamicin
Area of Science:
- Ototoxicity and Auditory Neuroscience
- Cellular Biology of Hearing
Background:
- Gentamicin is an ototoxic antibiotic known to cause hearing loss.
- The precise mechanism of gentamicin-induced damage to inner hair cells (IHCs) and their synapses remains incompletely understood.
Purpose of the Study:
- To investigate the spatiotemporal pattern of gentamicin uptake in IHCs.
- To determine the relationship between gentamicin accumulation and hearing threshold changes.
- To explore the potential impact of gentamicin on cochlear ribbon synapses.
Main Methods:
- Adult C57 mice received daily intraperitoneal injections of Texas Red-conjugated gentamicin for 14 days.
- Auditory brainstem response (ABR) tests assessed hearing thresholds.
- Immunostaining, confocal microscopy, and scanning electron microscopy (SEM) analyzed gentamicin distribution, synaptic marker expression (RIBEYE/CtBP2), and stereocilia morphology.
Main Results:
- Gentamicin distribution in IHCs was observed by day 4, with significant accumulation by day 7, coinciding with maximal hearing threshold elevation.
- Gentamicin accumulation levels at day 14 were similar to day 7.
- Uptake of gentamicin was consistently found at or near synaptic ribbons in IHCs from day 4 to day 14.
Conclusions:
- The dynamic distribution and accumulation of ototoxic gentamicin within IHCs suggest a direct impact on cochlear ribbon synapses.
- Gentamicin exposure may lead to synaptic interruption, contributing to the observed hearing loss.
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