Modulation of Presbycusis: Current Status and Future Directions

Willott, James F.; Chisolm, Theresa H.; Lister, Jennifer J.

doi:10.1159/000046129

Cited by 78 publications

(50 citation statements)

References 122 publications

(122 reference statements)

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“…Understanding of the interdependency of cochlear cell types for survival, along with shared risk factors by cell type, has benefited from the application of inbred mouse strains exhibiting very different aging characteristics. Many inbred and genetically engineered mutant lines usefully model specific aspects of human presbycusis (Willott 1991;Henry and McGinn 1992;Willott 2001;Ohlemiller 2006), and have helped clarify principles learned from other animals (Covell and Rogers 1957;Bohne et al 1990;Tarnowski et al 1991;Spicer and Schulte 2005a). As part of this process, inbred strains showing rapid progressive hearing loss…”

Section: Introductionmentioning

confidence: 99%

Divergent Aging Characteristics in CBA/J and CBA/CaJ Mouse Cochleae

Ohlemiller

Dahl

Gagnon

2010

JARO

100

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Two inbred mouse strains, CBA/J and CBA/CaJ, have been used nearly interchangeably as 'good hearing' standards for research in hearing and deafness. We recently reported, however, that these two strains diverge after 1 year of age, such that CBA/CaJ mice show more rapid elevation of compound action potential (CAP) thresholds at high frequencies (Ohlemiller, Brain Res. 1277: 70-83, 2009). One contributor is progressive decline in endocochlear potential (EP) that appears only in CBA/CaJ. Here, we explore the cellular bases of threshold and EP disparities in old CBA/J and CBA/CaJ mice. Among the major findings, both strains exhibit a characteristic age (∼18 months in CBA/J and 24 months in CBA/CaJ) when females overtake males in sensitivity decline. Strain differences in progression of hearing loss are not due to greater hair cell loss in CBA/ CaJ, but instead appear to reflect greater neuronal loss, plus more pronounced changes in the lateral wall, leading to EP decline. While both male and female CBA/CaJ show these pathologies, they are more pronounced in females. A novel feature that differed sharply by strain was moderate loss of outer sulcus cells (or 'root' cells) in spiral ligament of the upper basal turn in old CBA/CaJ mice, giving rise to deep indentations and void spaces in the ligament. We conclude that CBA/CaJ mice differ both quantitatively and qualitatively from CBA/J in age-related cochlear pathology, and model different types of presbycusis.

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Section: Introductionmentioning

confidence: 99%

Divergent Aging Characteristics in CBA/J and CBA/CaJ Mouse Cochleae

Ohlemiller

Dahl

Gagnon

2010

JARO

100

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“…In addition, LCAR modulates the intramitochondrial acylCoA͞CoA ratio and is responsible for scavenging toxic compounds before they have a chance to accumulate in the mitochondria. Interestingly, LCAR and one of its esters, acetyl-L-carnitine (ALCAR), have been shown to reverse many ageassociated deficits in cellular function linked to oxidative damage and mitochondrial decay, including age-related hearing loss (presbycusis) (8)(9)(10).…”

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confidence: 99%

Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss

Kalinec

Fernández-Zapico

Urrutia

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Gentamicin is a widely used ototoxic agent. In this study, we shed light on the mechanisms underlying gentamicin-induced hearing loss. More importantly, we demonstrate in vivo and in vitro the effectiveness of a strategy for preventing drug-induced hearing loss using L Together, these results outline pathways for gentamicin-induced hearing loss and its prevention and assign a key role to Hrk in these processes. Thus, our data offer a conceptual framework for designing clinical trials using a safe micronutrient, LCAR, as a simple preventive strategy for iatrogenically induced ototoxicity.apoptosis ͉ ototoxicity ͉ L-carnitine ͉ extracellular signal-regulated kinase 1͞2 ͉ HEI-OC1 cells

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“…En effet, 70 % des personnes de plus de 65 ans ont des problèmes auditifs [11]. La presbyacousie est une pathologie multifactorielle faisant intervenir une combinaison de facteurs individuels et environnementaux.…”

Section: Contribution Des Modèles Murins à La Compréhension De La Preunclassified