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Beyer, Lisa A.; Odeh, Hana M.; Probst, Frank J.; Lambert, Erica H.; Dolan, David F.; Camper, Sally A.; Kohrman, David C.; Raphael, Yehoash

doi:10.1023/a:1026515619443

Cited by 71 publications

(18 citation statements)

References 16 publications

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“…7C, red), and they were never seen in control or TTS cochleas. These resembled ‘cytocauds’, the cable-like actin aggregates seen in IHCs and vestibular hair cells from rodents with genetically aberrant stereocilia (Anniko et al, 1980; Sobin et al, 1982; Beyer et al, 2000; Kanzaki et al, 2002; Mathur et al, 2015), suggesting the dysmorphology may be related to noise-induced stereocilia damage. Second, cytoplasmic extrusions were observed in noise-exposed IHCs (Fig.…”

Section: Resultsmentioning

confidence: 93%

Noise-induced cochlear synaptopathy in rhesus monkeys ( Macaca mulatta )

et al. 2017

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Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss. Non-human primates appear to be less vulnerable to noise-induced hair-cell loss than rodents, but their susceptibility to synaptopathy has not been studied. Because establishing a non-human primate model may be important in the development of diagnostics and therapeutics, we examined cochlear innervation and the damaging effects of acoustic overexposure in young adult rhesus macaques. Anesthetized animals were exposed bilaterally to narrow-band noise centered at 2 kHz at various sound-pressure levels for 4 hrs. Cochlear function was assayed for up to 8 weeks following exposure via auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs). A moderate loss of synaptic connections (mean of 12-27% in the basal half of the cochlea) followed temporary threshold shifts (TTS), despite minimal hair-cell loss. A dramatic loss of synapses (mean of 50-75% in the basal half of the cochlea) was seen on IHCs surviving noise exposures that produced permanent threshold shifts (PTS) and widespread hair-cell loss. Higher noise levels were required to produce PTS in macaques compared to rodents, suggesting that primates are less vulnerable to hair-cell loss. However, the phenomenon of noise-induced cochlear synaptopathy in primates is similar to that seen in rodents.

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Section: Resultsmentioning

confidence: 93%

Noise-induced cochlear synaptopathy in rhesus monkeys ( Macaca mulatta )

et al. 2017

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“…Specimens for transmission electron microscope (TEM) were prepared as described in a previous report (Beyer et al, 2000). Briefly, cochlear tissues embedded in Epon were sectioned at the OSL opening near the habenula perforata using a Leica Ultracut R microtome at 80 nm thicknesses and collected onto mesh grids.…”

Section: Methodsmentioning

confidence: 99%

Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus

et al. 2016

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In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus. However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT-induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and cochlear nucleus neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination.

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“…Adult Chd7 Gt/+ and wild type mice were anesthetized, and ABRs recorded in an electrically and acoustically shielded chamber (Acoustic Systems, Austin, TX USA) as previously described (Beyer et al, 2000; Karolyi et al, 2007). Briefly, needle electrodes were placed at vertex (active) and the test ear (reference) and contralateral (ground) ear pinnae.…”

Section: Methodsmentioning

confidence: 99%

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome

et al. 2011

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Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by Prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7Gt/+ mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7Gt/+ mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7Gt/+ mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7Gt/+ mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears.

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Untitled

Cited by 71 publications

References 16 publications

Noise-induced cochlear synaptopathy in rhesus monkeys ( Macaca mulatta )

Noise-induced cochlear synaptopathy in rhesus monkeys ( Macaca mulatta )

Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome

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