Accession Number : ADA624471


Title :   Prevention of Noise Damage to Cochlear Synapses


Descriptive Note : Annual rept. 30 Sep 2014-29 Sep 2015


Corporate Author : IOWA UNIV IOWA CITY


Personal Author(s) : Green, Steven


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA624471


Report Date : Oct 2015


Pagination or Media Count : 20


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.


Descriptors :   *AUDITORY DEFECTS , *COCHLEA , *DAMAGE , *SYNAPSE , AMPLITUDE , CELLS(BIOLOGY) , CLINICAL MEDICINE , CULTURES(BIOLOGY) , DEAFNESS , GANGLIA , GLUTAMIC ACID , IN VITRO ANALYSIS , IONS , NERVE CELLS , NOISE(SOUND) , PREVENTION , RECEPTOR SITES(PHYSIOLOGY) , RESPONSE(BIOLOGY) , THRESHOLDS(PHYSIOLOGY) , TRAUMA


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE