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

• Hamaguchi, Kiyomi

• Yamamoto, Norio

• Nakagawa, Takayuki

• Furuyashiki, Tomoyuki

• Narumiya, Shuh

• Ito, Juichi

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.

Journal

• Neuropharmacology

  Neuropharmacology 62 (4), 1841-1847, 2012-03

  Elsevier Ltd.

Keywords

• Cochlea
• Hair cell
• Hearing loss
• Noise trauma
• PGE-type receptor

Details

• CRID: 1050564285679869056
• NII Article ID: 120003874264
• NII Book ID: AA11540719
• ISSN: 00283908
• HANDLE: 2433/153283
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles