title: Mitochondria toxin-induced acute cochlear cell death indicates cellular activity-correlated energy consumption.
abstract: The different cell types within the cochlea may have a specific contribution to the pathological changes during metabolism failure, which may provide clues for developing novel strategies for inner ear therapy. In order to evaluate activity-correlated cell death during metabolism failure in the cochlea, 3-nitropropionic acid was used to irreversibly inhibit the respiratory chain. Dose-response of the cochlear cells to 3-nitropropionic acid was analyzed in vitro. 3-Nitropropionic acid was administered onto the round window of guinea pigs. Cell death was identified by terminal transferase labeling the free 3'OH breaks in the DNA strands in vivo and propidium iodide nuclear permeation in vitro. As a result, 23.6 and 96.3 % cell death were induced by 10 and 100 mM 3-nitropropionic acid, respectively, in vitro. In the guinea pigs, 500 mM 3-nitropropionic acid induced vestibular dysfunction and severe to profound hearing losses. The cells that are the most sensitive to 3-nitropropionic acid treatment include the stria marginal and intermediate cells, epithelial cells of the Reissner's membrane, and spiral ligament fibrocytes (types II and V). Moderate sensitive cells were satellite fibrocytes of the spiral limbic central zone, osteocytes of the cochlear shell, hair cells, and spiral ganglion cells. Reduction of neurofilament in the soma and periphery processes of spiral ganglion cells occurred after the exposure. These results may be relevant to the mechanisms of injury in sudden onset sensorineural hearing loss and hazardous substance exposure-induced hearing loss.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. Jing.Zou@uta.fi
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weikai
authors.initials: W
authors.lastname: Zhang
authors.forename: Dennis
authors.initials: D
authors.lastname: Poe
authors.forename: Suoqiang
authors.initials: S
authors.lastname: Zhai
authors.forename: Shiming
authors.initials: S
authors.lastname: Yang
authors.forename: Ilmari
authors.initials: I
authors.lastname: Pyykkö
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D003051:Cochlea / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000502:physiology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000473:pathology*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009574:Nitro Compounds; D011422:Propionates; D051381:Rats; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000473:pathology*
chemical_list: D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid