Macrophages Promote Repair of Inner Hair Cell Ribbon Synapses following Noise-Induced Cochlear Synaptopathy

Area of Science:

• Neuroscience
• Immunology
• Auditory Science

Background:

• Noise exposure can cause cochlear synaptopathy, leading to hidden hearing loss.
• The role of cochlear macrophages in synaptic repair after noise damage is not fully understood.

Purpose of the Study:

• To investigate the precise role of cochlear macrophages in synaptic degeneration and repair following noise-induced synaptopathy.
• To determine if macrophages are necessary and sufficient for restoring cochlear synapses and function.

Main Methods:

• Elimination of cochlear macrophages using the CSF1R inhibitor PLX5622 in mice.
• Assessment of hearing loss, synapse loss, and cochlear neuron survival after noise exposure in the presence and absence of macrophages.
• Evaluation of synaptic repair and functional recovery upon macrophage repopulation.

Main Results:

• Macrophage elimination did not affect initial hearing or synapse loss but significantly reduced synaptic repair 30 days post-noise exposure.
• Macrophage repopulation enhanced synaptic repair and functional recovery.
• Absence of macrophages augmented cochlear neuron loss, while their presence preserved neurons.

Conclusions:

• Cochlear macrophages are not involved in synaptic degeneration but are crucial for synaptic repair and functional recovery after noise-induced synaptopathy.
• These findings reveal a novel role for innate immune cells in auditory synapse regeneration, offering potential therapeutic targets for hearing loss.