FVB/NJ Mice Demonstrate a Youthful Sensitivity to Noise-Induced Hearing Loss and Provide a Useful Genetic Model for the Study of Neural Hearing Loss

Ho, Maria K.; Li, Xin; Wang, Juemei; Ohmen, Jeffrey D.; Friedman, Rick A.

doi:10.1159/000357770

Cited by 11 publications

(8 citation statements)

References 71 publications

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“…The recovery of thresholds for DPOAE measurements at day 14 post-treatment combined with the incomplete recovery of ABR thresholds at day 14 post-treatment suggests that loss of hearing may not be directly dependent upon outer hair cell activity for FVB/nJ mice within the acoustic damage regimes tested. These results are consistent with previous reports of FVB/nJ noise sensitivity 13 .…”

Section: Resultssupporting

confidence: 94%

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Noise exposure modulates cochlear inner hair cell ribbon volumes, correlating with changes in auditory measures in the FVB/nJ mouse

Paquette

Gilels

White

2016

Sci Rep

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Cochlear neuropathy resulting from unsafe noise exposure is a life altering condition that affects many people. This hearing dysfunction follows a conserved mechanism where inner hair cell synapses are lost, termed cochlear synaptopathy. Here we investigate cochlear synaptopathy in the FVB/nJ mouse strain as a prelude for the investigation of candidate genetic mutations for noise damage susceptibility. We used measurements of auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to assess hearing recovery in FVB/nJ mice exposed to two different noise levels. We also utilized confocal fluorescence microscopy in mapped whole mount cochlear tissue, in conjunction with deconvolution and three-dimensional modeling, to analyze numbers, volumes and positions of paired synaptic components. We find evidence for significant synapse reorganization in response to both synaptopathic and sub-synaptopathic noise exposures in FVB/nJ. Specifically, we find that the modulation in volume of very small synaptic ribbons correlates with the presence of reduced ABR peak one amplitudes in both levels of noise exposures. These experiments define the use of FVB/nJ mice for further genetic investigations into the mechanisms of noise damage. They further suggest that in the cochlea, neuronal-inner hair cell connections may dynamically reshape as part of the noise response.

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Section: Resultssupporting

confidence: 94%

“…Second, FVB/nJ hearing thresholds are stable for the first 10 months of life 12 . Third, FVB/nJ mice have a youthful sensitivity to noise damage, similar to CBA/CaJ 13 . Fourth, there are a large number of well-characterized genetic mutations on this mouse strain for technical reasons 14 15 16 17 .…”

mentioning

confidence: 99%

Noise exposure modulates cochlear inner hair cell ribbon volumes, correlating with changes in auditory measures in the FVB/nJ mouse

Paquette

Gilels

White

2016

Sci Rep

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“…We exposed the mice to noise before performing the trans-tympanic injections to ensure that the noise exposure was as specified and was not mitigated by procedure-induced temporal hearing loss ( Fig. 4, A–C ), to ensure that the damage was similar to that recorded in previous studies ( Maison et al, 2002 ; Ho et al, 2014 ) on noise damage in FVB mice, and to mimic certain clinical conditions in which protective drugs might be delivered after exposure. Because of the mixed-strain CD1/FVB/129/C57BL/6 background, CDK2 KO and WT littermate mice exhibited greater variability in their ABR thresholds than did FVB or 129/C57BL/6 mice, especially at 32 kHz ( Fig.…”

Section: Methodsmentioning

confidence: 99%

CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss

Teitz

Fang

Goktug

et al. 2018

Journal of Experimental Medicine

108

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“…While others have reported no difference in auditory thresholds between young adult homozygous Sirt3-KO and wild-type littermates [18,19,31], those experiments were performed using mice of the C57BL/6J strain. To assess the response to noise damage, we bred Sirt3-KO mice to FVB/nJ mice, which have good hearing and a youthful susceptibility to noise damage [32]. Littermates of both genotypes underwent hearing tests at around P50.…”

Section: Resultsmentioning

confidence: 99%

SIRT3 promotes auditory function in young adult FVB/nJ mice but is dispensable for hearing recovery after noise exposure

et al. 2020

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Noise-induced hearing loss (NIHL) affects millions of people worldwide and presents a large social and personal burden. Pharmacological activation of SIRT3, a regulator of the mitochondrial oxidative stress response, has a protective effect on hearing thresholds after traumatic noise damage in mice. In contrast, the role of endogenously activated SIRT3 in hearing recovery has not been established. Here we tested the hypothesis that SIRT3 is required in mice for recovery of auditory thresholds after a noise exposure that confers a temporary threshold shift (TTS). SIRT3-specific immunoreactivity is present in outer hair cells, around the post-synaptic regions of inner hair cells, and faintly within inner hair cells. Prior to noise exposure, homozygous Sirt3-KO mice have slightly but significantly higher thresholds than their wild-type littermates measured by the auditory brainstem response (ABR), but not by distortion product otoacoustic emissions (DPOAE). Moreover, homozygous Sirt3-KO mice display a significant reduction in the progression of their peak 1 amplitude at higher frequencies prior to noise exposure. After exposure to a single sub-traumatic noise dose that does not permanently reduce cochlear function, compromise cell survival, or damage synaptic structures in wild-type mice, there was no difference in hearing function between the two genotypes, measured by ABR and DPOAE. The numbers of hair cells and auditory synapses were similar in both genotypes before and after noise exposure. These loss-of-function studies complement previously published gain-of-function studies and help refine our understanding of SIRT3's role in cochlear homeostasis under different damage paradigms. They suggest that SIRT3 may promote spiral ganglion neuron function. They imply that cellular mechanisms of homeostasis, in addition to the mitochondrial oxidative stress response, act to restore hearing after TTS. Finally, we present a novel application of a biomedical statistical analysis for identifying changes between peak 1 amplitude progressions in ABR waveforms after damage.

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FVB/NJ Mice Demonstrate a Youthful Sensitivity to Noise-Induced Hearing Loss and Provide a Useful Genetic Model for the Study of Neural Hearing Loss

Cited by 11 publications

References 71 publications

Noise exposure modulates cochlear inner hair cell ribbon volumes, correlating with changes in auditory measures in the FVB/nJ mouse

Noise exposure modulates cochlear inner hair cell ribbon volumes, correlating with changes in auditory measures in the FVB/nJ mouse

CDK2 inhibitors as candidate therapeutics for cisplatin- and noise-induced hearing loss

SIRT3 promotes auditory function in young adult FVB/nJ mice but is dispensable for hearing recovery after noise exposure

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