Gentamicin administration leads to synaptic dysfunction in inner hair cells.

Area of Science:

• Ototoxicology
• Neuroscience
• Cell Biology

Background:

• Aminoglycosides cause ototoxicity and hearing loss, primarily by affecting hair cells.
• Recent evidence suggests aminoglycosides also damage ribbon synapses in inner hair cells (IHCs).
• Mechanisms and functional consequences of aminoglycoside-induced ribbon synapse loss are not fully understood.

Purpose of the Study:

• To investigate the impact of gentamicin on ribbon synapses in IHCs.
• To elucidate the underlying molecular mechanisms of gentamicin-induced synaptic damage.
• To explore the functional consequences of synaptic alterations on auditory function.

Main Methods:

• Gentamicin was administered to C57BL/6J mice.
• Auditory brainstem response (ABR) was measured.
• Immunofluorescence staining, patch-clamp recording, and proteomics were employed.
• Western blotting was used to analyze protein expression.

Main Results:

• Gentamicin induced elevated ABR thresholds and reduced ABR wave I amplitude.
• Ribbon synapse loss was observed in IHCs.
• Patch-clamp recordings showed reduced calcium currents and altered calcium dependency in IHCs.
• Gentamicin downregulated myosin VI expression in IHCs, impacting synaptic vesicle recycling and exocytosis.

Conclusions:

• Gentamicin treatment causes synaptic dysfunction in IHCs.
• Downregulation of myosin VI plays a critical role in gentamicin-induced synaptic damage.
• These findings highlight synaptic alterations as a key mechanism of aminoglycoside ototoxicity.