title: 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.affiliation: Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyoku, Kyoto 606-8507, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Hamaguchi
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
mesh_terms: D000818:Animals; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000378:metabolism*; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects / Q000502:physiology; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D008738:Methyl Ethers; C461399:ONO-AE1-329; D058309:Receptors, Prostaglandin E, EP4 Subtype