Prevention of Noise Damage to Cochlear Synapses
Abstract
Noise-induced synaptopathy is the result of excitotoxic trauma to cochlear synapses due to glutamate released from the hair cells. Excitotoxic trauma damages the postsynaptic cell by causing entry of Ca2+ ions. We have identified the route of Ca2+ entry as via Ca2+-permeable AMPA-type glutamate receptors (CP-AMPARs.) We showed that a selective blocker of CP-AMPARs -- the anandamide compound IEM-1460 -- reduces synaptopathy caused by application of the glutamate agonist kainic acid to cochlear explants in vitro. We further showed that IEM-1460 inhibits KA-dependent Ca2+ entry into spiral ganglion neurons in vitro. Most significantly, we have used physiological measures -- auditory brainstem response threshold and amplitude -- and direct counting of synapses in confocal microscope images to demonstrate essentially complete prevention of synaptopathy and hearing impairment in noise-exposed mice without significant elevation of normal hearing threshold. This suggests that selective CP-AMPAR blockers such as IEM-1460 could be effective in protecting cochlear synapses from noise-induced synaptopathy and preventing the consequent hearing impairment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- ADA624471
Entities
People
- Steven H Green
Organizations
- University of Iowa