title: A novel animal model of hearing loss caused by acute endoplasmic reticulum stress in the cochlea.
abstract: Many stimuli such as ischemia, hypoxia, heat shock, amino acid starvation, and gene mutation, exhibit a cellular response called endoplasmic reticulum (ER) stress. ER stress induces expression of a series of genes, leading to cell survival or apoptosis. Previously, we found that in an animal model of hearing loss caused by acute mitochondrial dysfunction, several ER stress markers including C/EBP homologous protein were induced in the cochlear lateral wall. To elucidate the mechanism of hearing loss caused by ER stress, we established a novel animal model of hearing loss by perilymphatic perfusion of tunicamycin, an ER stress activator that inhibits N-acetylglucosamine transferases. Subacute and progressive hearing loss was observed at all sound frequencies studied, and stimulation of ER stress marker genes was noted in the cochlea. The outer hair cells were the most sensitive to ER stress in the cochlea. Electron microscopic analysis demonstrated degeneration of the subcellular organelles of the inner hair cells and nerve endings of the spiral ganglion cells. This newly established animal model of hearing loss from ER stress will provide additional insight into the mechanism of sensorineural hearing loss.
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs (NISO), National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujinami
authors.forename: Hideki
authors.initials: H
authors.lastname: Mutai
authors.forename: Kunio
authors.initials: K
authors.lastname: Mizutari
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics; D000818:Animals; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005786:Gene Expression Regulation; D034381:Hearing Loss / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051742:Transcription Factor CHOP / Q000235:genetics; D014415:Tunicamycin / Q000008:administration & dosage
chemical_list: C497110:Atf4 protein, rat; C497251:Ddit3 protein, rat; D008562:Membrane Glycoproteins; C053387:endoplasmin; D014415:Tunicamycin; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP