title: Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea.
abstract: Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model. Marked degeneration was detected in type 2 fibrocytes in the spiral prominence, type 4 fibrocytes in the spiral ligament, marginal cells and intermediate cells in the stria vascularis 3 h after 3-NP administration; these changes were progressive for at least 14 days. Less prominent degeneration was detected in type 1 and type 3 fibrocytes in the spiral ligament. These results indicate that permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by cellular degeneration in the lateral wall of the cochlea, and suggest that therapy of cochlear hearing loss due to acute energy failure may be achieved through protection and regeneration of the cochlear lateral wall.
authors.affiliation: Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo 152-8902, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hoya
authors.forename: Kazusaku
authors.initials: K
authors.lastname: Kamiya
authors.forename: Masato
authors.initials: M
authors.lastname: Fujii
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ogawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
mesh_terms: D000208:Acute Disease; D000818:Animals; D001309:Auditory Threshold; D015834:Cochlear Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D003292:Convulsants / Q000633:toxicity; D004734:Energy Metabolism; D005260:Female; D008854:Microscopy, Electron; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009574:Nitro Compounds; D009925:Organ of Corti / Q000473:pathology* / Q000648:ultrastructure; D011422:Propionates / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000473:pathology / Q000648:ultrastructure
chemical_list: D003292:Convulsants; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid