Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice

McFadden, Sandra L.; Ding, Dalian; Burkard, Robert; Jiang, Haiyan; Reaume, Andrew G.; Flood, Dorothy G.; Salvi, Richard

doi:10.1002/(sici)1096-9861(19991011)413:1<101::aid-cne7>3.0.co;2-l

Cited by 125 publications

(58 citation statements)

References 32 publications

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“…Furthermore, it is flatly contradicted by the systematic biases in mtDNA segregation reported in human cultured cells [35], and in mouse solid tissues [59]. Free radical production is concentrated in the mitochondrial compartment of the cell, as illustrated by the severe pathologies resulting from ablation of the mitochondrial [60], but not the cytosolic [61], form of superoxide dismutase. However, to what extent a 'vicious cycle' of defective mtDNA, impaired mitochondrial respiration with increased oxygen radical formation, followed by further DNA mutation, contributes to loss of mitochondrial function is debated, as is the role of mitophagy in clearing deleterious mtDNAs [62,63].…”

Section: Alternative Selection Mechanisms For Pathological Variants Amentioning

confidence: 99%

The road to rack and ruin: selecting deleterious mitochondrial DNA variants

Holt¹,

Speijer

Kirkwood

2014

Phil. Trans. R. Soc. B

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Mitochondria constitute the major energy-producing compartment of the eukaryotic cell. These organelles contain many molecules of DNA that contribute only a handful of proteins required for energy production. Mutations in the DNA of mitochondria were identified as a cause of human disease a quarter of a century ago, and they have subsequently been implicated in ageing. The process whereby deleterious variants come to dominate a cell, tissue or human is the subject of debate. It is likely to involve multiple, often competing, factors, as selection pressures on mitochondrial DNA can be both indirect and intermittent, and are subjected to rapid change. Here, we assess the different models and the prospects for preventing the accumulation of deleterious mitochondrial DNA variants with time.

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Section: Alternative Selection Mechanisms For Pathological Variants Amentioning

confidence: 99%

The road to rack and ruin: selecting deleterious mitochondrial DNA variants

Holt¹,

Speijer

Kirkwood

2014

Phil. Trans. R. Soc. B

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“…The procedures for preparing and analyzing mouse inner ears have been described in detail in previous reports (McFadden et al, 1999a;McFadden et al, 1999b: Willott et al, 2006. Briefly, the organ of Corti was carefully microdissected out from base to apex, and specimens stained with Ehrlich's hematoxylin solution (Ding et al, 2001).…”

Section: Cytocochleogramsmentioning

confidence: 99%

Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency augmented acoustic environment: Auditory brainstem response thresholds and cytocochleograms

et al. 2006

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Gonadectomized and surgically intact adult C57BL/6J (B6) mice of both sexes were exposed for 12 hours nightly to a high-frequency augmented acoustic environment (AAE): repetitive bursts of a half-octave noise band centered at 20 kHz, 70 dB SPL. The effects of sex, gonadectomy, and AAE treatment on genetic progressive hearing loss (exhibited by B6 mice) were evaluated by obtaining auditory brainstem response thresholds at ages 3-, 6-, and 9-months; hair cell counts (cytocochleograms) were obtained at 9 months. A sex difference in the rate of genetic progressive hearing loss in B6 mice (observed by earlier studies) was confirmed, with females exhibiting a faster rate of threshold elevations and more severe loss of hair cells at age 9 months. Gonadectomy had no consistent effects on the rate or severity of hearing loss in nonexposed mice of either sex. An unexpected finding was that the high-frequency AAE treatment caused additional ABR threshold elevations and hair cell loss. In an earlier study, the same high-frequency AAE treatment on DBA/ 2J mice ameliorated hearing loss. The most severe AAE-induced losses occurred in surgically intact females, suggesting a potentiating effect of ovarian hormone(s).

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“…Mitochondrial deletions increase with age and correlate with hearing loss in rats [22]. Furthermore, age-related hearing loss developed earlier and was more severe in mice with genes for SOD deleted [16,17,15]. However, little is known about the type of reactive oxygen species that may be involved in the aging process in the inner ear, which tissues and cells (sensory cells and nerve fibers versus supporting structures) are affected and whether the time course of their emergence correlates with the appearance of morphological and functional deficits.…”

Section: Introductionmentioning

confidence: 98%

Oxidative imbalance in the aging inner ear

Jiang

Talaska

Schacht

et al. 2007

Neurobiology of Aging

178

122

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The mammalian inner ear loses its sensory cells with advancing age, accompanied by a functional decrease in balance and hearing. This study investigates oxidant stress in the cochlea of aging male CBA/J mice. Glutathione-conjugated proteins, markers of H 2 O 2 -mediated oxidation, began to increase at 12 months of age; 4-hydroxynonenal and 3-nitrotyrosine, products of hydroxyl radical and peroxynitrite action, respectively, were elevated by 18 months. Immunoreactivity to these markers was stronger in the supporting cells (Deiters and pillar cells) than the sensory cells. It appeared later (23 months) in the nerve fibers of the spiral ganglion and in the stria vascularis and spiral ligament. Conversely, antioxidant proteins (AIF) and enzymes (SOD2) decreased by 18 months in the organ of Corti (including the sensory cells) and nerve fibers but not in the stria vascularis. These results suggest the presence of different reactive oxygen species and differential time courses of oxidative changes in individual tissues of the aging cochlea. An imbalance of redox status may be a component of age-related hearing loss.

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Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice

Cited by 125 publications

References 32 publications

The road to rack and ruin: selecting deleterious mitochondrial DNA variants

The road to rack and ruin: selecting deleterious mitochondrial DNA variants

Effects of exposing gonadectomized and intact C57BL/6J mice to a high-frequency augmented acoustic environment: Auditory brainstem response thresholds and cytocochleograms

Oxidative imbalance in the aging inner ear

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