No longer falling on deaf ears: Mechanisms of degeneration and regeneration of cochlear ribbon synapses

Wan, Guoqiang; Corfas, Gabriel

doi:10.1016/j.heares.2015.04.008

Cited by 29 publications

(31 citation statements)

References 191 publications

(255 reference statements)

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“…The magnitude of ARHL could best be reduced by protection from noise exposure that directly leads to outer hair cell degeneration (Liberman & Kiang, ) and ultimately neuronal degeneration (Kujawa & Liberman, ) and inflammation (Hirose et al, ; Tornabene et al, ). Though not reviewed here, several groups are working on therapeutic, pharmaceutical strategies for addressing age‐related cochlear degeneration (Bielefeld, Tanaka, Chen, & Henderson, ; Frisina, Ding, Zhu, & Walton, ; Kalinec, Lomber, Urrutia, & Kalinec, ; Seidman, ; Seidman, Khan, Tang, & Quirk, ; Wan & Corfas, ) and the future might then see less debilitation from ARHL.…”

Section: Discussionmentioning

confidence: 99%

Pathology and mechanisms of cochlear aging

Keithley

2019

J of Neuroscience Research

164

106

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Presbycusis, or age‐related hearing loss (ARHL), occurs in most mammals with variations in the age of onset, rate of decline, and magnitude of degeneration in the central nervous system and inner ear. The affected cochlear structures include the stria vascularis and its vasculature, spiral ligament, sensory hair cells and auditory neurons. Dysfunction of the stria vascularis results in a reduced endocochlear potential. Without this potential, the cochlear amplification provided by the electro‐motility of the outer hair cells is insufficient, and a high‐frequency hearing‐loss results. Degeneration of the sensory cells, especially the outer hair cells also leads to hearing loss due to lack of amplification. Neuronal degeneration, another hallmark of ARHL, most likely underlies difficulties with speech discrimination, especially in noisy environments. Noise exposure is a major cause of ARHL. It is well‐known to cause sensory cell degeneration, especially the outer hair cells at the high frequency end of the cochlea. Even loud, but not uncomfortable, sound levels can lead to synaptopathy and ultimately neuronal degeneration. Even in the absence of a noisy environment, aged cells degenerate. This pathology most likely results from damage to mitochondria and contributes to degenerative changes in the stria vascularis, hair cells, and neurons. The genetic underpinnings of ARHL are still unknown and most likely involve various combinations of genes. At present, the only effective strategy for reducing ARHL is prevention of noise exposure. If future strategies can improve mitochondrial activity and reduce oxidative damage in old age, these should also bring relief.

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Section: Discussionmentioning

confidence: 99%

Pathology and mechanisms of cochlear aging

Keithley

2019

J of Neuroscience Research

164

106

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“…Although there is spontaneous regeneration of spiral ganglion cell peripheral dendrites and of their synaptic connections with inner hair cells in the neonatal (P6) rat ear after drug-induced synaptopathy (Wang and Green, 2011), there is no evidence for any regeneration of cochlear nerve peripheral synapses in the adult mouse after noise-induced synaptopathy (Kujawa and Liberman, 2009). On the other hand, noise-induced synaptopathy can be partially rescued by overexpression of neurotrophin-3 (Wan and Corfas, 2015), a molecular signal of particular importance to cochlear neuronal survival in the adult. It is possible that thiamine-induced synaptopathy could also be rescued in similar fashion, given that, as with noise-induced and age-related synaptopathies (Kujawa and Liberman, 2009; Sergeyenko et al, 2013), the loss of spiral ganglion cells seems significantly delayed with respect to the loss of synapses (Fig.…”

Section: Discussionmentioning

confidence: 99%

Perinatal thiamine deficiency causes cochlear innervation abnormalities in mice

et al. 2016

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Neonatal thiamine deficiency can cause auditory neuropathy in humans. To probe the underlying cochlear pathology, mice were maintained on a thiamine-free or low-thiamine diet during fetal development or early postnatal life. At postnatal ages from 18 days to 22 wks, cochlear function was tested and cochlear histopathology analyzed by plastic sections and cochlear epithelial whole-mounts immunostained for neuronal and synaptic markers. Although none of the thiamine-deprivation protocols resulted in any loss of hair cells or any obvious abnormalities in the non-sensory structures of the cochlear duct, all the experimental groups showed significant anomalies in the afferent or efferent innervation. Afferent synaptic counts in the inner and outer hair cell areas were reduced, as was the efferent innervation density in both the outer and inner hair cell areas. As expected for primary neural degeneration, the thresholds for distortion product otoacoustic emissions were not affected, and as expected for subtotal hair cell de-afferentation, the suprathreshold amplitudes of auditory brainstem responses were more affected than the response thresholds. We conclude that the auditory neuropathy from thiamine deprivation could be produced by loss of inner hair cell synapses.

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“…If cochlear synaptopathy is ultimately determined to be reversible, the potential for temporary cochlear synaptopathic damage will be difficult, if not impossible, to distinguish from temporary OHC damage and temporary excitotoxic swelling. Finally, regardless of whether cochlear synaptopathy is induced by noise, or a function of aging, new research is necessary to fully identify mechanisms associated with drug-induced regeneration of synapses (Wan et al 2014;Wan and Corfas 2015;Suzuki, Corfas, and Liberman 2016). These observations of synaptogenesis raise hope that a "cure" could be available, if human cochlear synaptopathy becomes possible to diagnose using test batteries including elements such as those described here.…”

Section: Conclusion and Challenges To The Fieldmentioning

confidence: 98%

Effects of noise exposure on auditory brainstem response and speech-in-noise tasks: a review of the literature

Prell

2018

International Journal of Audiology

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Objective: Short-term noise exposure that induces transient changes in thresholds has induced permanent cochlear synaptopathy in multiple species. Here, the literature was reviewed to gain translational insight into the relationships between noise exposure, ABR metrics, speech-in-noise performance and TTS in humans. Design: PubMed-based literature search, retrieval and review of full-text articles. Study Sample: Peerreviewed literature identified using PubMed search. Results: Permanent occupational noise-induced hearing loss (NIHL) is frequently accompanied by abnormal ABR amplitude and latency. In the absence of NIHL, there are mixed results for relationships between noise exposure and ABR metrics. Interpretation of speech-in-noise deficits is difficult as both cochlear synaptopathy and outer hair cell (OHC) loss can drive deficits. Reductions in Wave I amplitude during TTS may reflect temporary OHC pathology rather than cochlear synaptopathy. Use of diverse protocols across studies reduces the ability to compare outcomes across studies. Conclusions: Longitudinal ABR and speech-in-noise data collected using consistent protocols are needed. Although speech-in-noise testing may not reflect cochlear synaptopathy, speech-in-noise testing should be completed as part of a comprehensive test battery to provide the objective measurement of patient difficulty.

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No longer falling on deaf ears: Mechanisms of degeneration and regeneration of cochlear ribbon synapses

Cited by 29 publications

References 191 publications

Pathology and mechanisms of cochlear aging

Pathology and mechanisms of cochlear aging

Perinatal thiamine deficiency causes cochlear innervation abnormalities in mice

Effects of noise exposure on auditory brainstem response and speech-in-noise tasks: a review of the literature

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