A novel animal model of acute cochlear mitochondrial dysfunction.
Acute mitochondrial dysfunction in the cochlea is likely to result in hearing loss as a consequence of local energy shortage, similar to ischemia- or noise-induced hearing loss. To establish an animal model of acute cochlear mitochondrial dysfunction, we applied a mitochondrial toxin, 3-nitropropionic acid (3-NP) in the rat cochlea. Rats treated with 500mM 3-NP exhibited permanent threshold shifts in acoustic brainstem response while the same volume of 300mM 3-NP caused temporary threshold shifts. Histological examination in the permanent threshold shift model revealed severe degeneration of fibrocytes within spiral ligament and spiral limbus, indicating these cells are vulnerable to acute mitochondrial dysfunction. This model represents a novel tool for investigating the pathophysiology of acute cochlear mitochondrial dysfunction.
Hoya
Noriyuki
N
Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan.
Okamoto
Yasuhide
Y
Kamiya
Kazusaku
K
Fujii
Masato
M
Matsunaga
Tatsuo
T
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D015834:Cochlear Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D028361:Mitochondrial Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009574:Nitro Compounds / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009574:Nitro Compounds; C032869:3-nonenylnitrolic acid