Role of PGE-type receptor 4 in auditory function and noise-induced hearing loss in mice.

Abstract

This study explored the physiological roles of PGE-type receptor 4 (EP4) in auditory function. EP4-deficient mice exhibited slight hearing loss and a reduction of distortion-product otoacoustic emissions (DPOAEs) with loss of outer hair cells (OHCs) in cochleae. After exposure to intense noise, these mice showed significantly larger threshold shifts of auditory brain-stem responses (ABRs) and greater reductions of DPOAEs than wild-type mice. A significant increase of OHC loss was confirmed morphologically in the cochleae of EP4-deficient mice. Pharmacological inhibition of EP4 had a similar effect to genetic deletion, causing loss of both hearing and OHCs in C57BL/6 mice, indicating a critical role for EP4 signaling in the maintenance of auditory function. Pharmacological activation of EP4 significantly protected OHCs against noise trauma, and attenuated noise-induced hearing loss in C57BL/6 mice. These findings suggest that EP4 signaling is necessary for the maintenance of cochlear physiological function and for cochlear protection against noise-induced damage, in particular OHCs. EP4 might therefore be an effective target for cochlear disease therapeutics.

• Authors: Kiyomi Hamaguchi, Norio Yamamoto, Takayuki Nakagawa, Tomoyuki Furuyashiki, Shuh Narumiya, Juichi Ito
• Journal: Neuropharmacology (Neuropharmacology) Vol. 62 Issue 4 Pg. 1841-7 (Mar 2012) ISSN: 1873-7064 [Electronic] England
• PMID: 22198478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Methyl Ethers
• ONO-AE1-329
• Receptors, Prostaglandin E, EP4 Subtype

Topics

• Animals
• Auditory Perception (drug effects, physiology)
• Cochlea (drug effects, metabolism)
• Evoked Potentials, Auditory, Brain Stem (drug effects, physiology)
• Hearing Loss, Noise-Induced (metabolism)
• Methyl Ethers (pharmacology)
• Mice
• Mice, Knockout
• Otoacoustic Emissions, Spontaneous (drug effects, physiology)
• Receptors, Prostaglandin E, EP4 Subtype (agonists, genetics, metabolism)
• Signal Transduction (drug effects, physiology)