Loss of Ribbon Synapses as an Early Stage of Age-Related Hearing Loss

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Researchers here provide evidence for loss of ribbon synapases in the inner ear to be an early stage of the neurodegeneration that leads to age-related deafness. Other evidence also points to loss of neural connections between ear and brain as the most important contributing cause in age-related deafness, more so than any loss of sensory hair cells in the inner ear that might take place. This points towards approaches to therapy that are primarily based on regeneration of neural connections, rather than provision of replacement cells. While there is some overlap between specific implementations of these strategies, they are quite different end goals.

Age-related hearing loss (ARHL), or presbycusis, is a progressive and pathological process that results from age-related degeneration of the cochlea and central auditory system. It affects almost half of individuals over the age of 75 years. It is characterized by significant elevations in the hearing threshold with reductions in speech discrimination and difficulty in localization of sound sources, particularly in noisy environments. Previous studies have shown that the loss of outer hair cells (OHCs), damage to the stereocilia, and degenerated alterations of the auditory nerves are possible mechanisms underlying ARHL. However, recent studies have reported that these degenerative morphological changes in the cochlea occur after the onset of the hearing disorder. For example, specific noise exposure can cause hearing loss coupled with intact cochlear hair cells, stereocilia, and spiral ganglion neurons (SGNs), which suggests that other cochlear components may be responsible for hearing loss.

Both the ototoxic drugs such as gentamicin, and noise exposure have been proposed to cause a loss of ribbon synapses, which account for hearing impairment. Ribbon synapses of the inner hair cells (IHCs) are formed on the cochlea with a powerful function specialized for encoding acoustic signals with high temporal precision over long periods. It has been reported that aging cochlea could form unexpected folded endings in the postsynaptic nerve terminals, suggesting that aging could affect the morphologies or function of ribbon synapses. However, it remains unclear whether the quantity and function of the ribbon synapse are initially disrupted and thus contribute to the consequent hearing loss during aging.

In this study, we aimed to verify whether cochlear ribbon synapses are vulnerable to aging insult in C57BL/6J mice, a widespread model for ARHL. We explored the correlation between the number and function of ribbon synapses and the reduction of hearing function in the early stage of aging. We found that the loss of cochlear ribbon synapses is an initial pathological event in the early stage of aging, which causes hearing loss and may consequently induce loss or damage to other cochlear components, such as IHCs, and SGNs.

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724364/

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source https://www.fightaging.org/archives/2020/12/loss-of-ribbon-synapses-as-an-early-stage-of-age-related-hearing-loss/