Noise-induced and age-related hearing loss:  new perspectives and potential therapies

Abstract

The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a “hidden hearing loss” for two reasons: 1) the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2) the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.

Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System

“…Our findings predict that hair cell defects will secondarily affect the development of auditory circuitry. Significantly, hearing loss can also be caused by loss of synaptic innervation of IHCs by SGNs (Liberman, 2017). Low-SR synapses seem to be particularly vulnerable to noise or ageing (Furman et al, 2013; Schmiedt et al, 1996).…”

Early neuronal processes interact with glia to establish a scaffold for orderly innervation of the cochlea

“…Our work suggests that peripheral glia are not only be permissive, but might in fact be able to actively encourage axon re-extension. In the cochlea, SGN processes lose their synapses and retract following exposure to excessively loud sounds in animal models 42 .…”

Progressive Dominant Hearing Loss (Autosomal Dominant Deafness‐41) and P2RX2 Gene Mutations: A Phenotype–Genotype Study

“…Sensorineural hearing loss remains the most common type of hearing loss. In adults, two of the main contributing factors to this hearing loss are age (presbycusis) and noise exposure . NIHL is a leading cause of sensory disability, despite the accelerating awareness of the hazards of sustained exposure to high‐level environmental and recreational sound in society.…”

“…Noise is known to stimulate ATP release in the cochlea where ATP affects sound transduction, the endocochlear potential, and neurotransmission . The ATP‐gated ion channel P2X2 receptor has been shown to underlie an intrinsic purinergic receptor‐based hearing adaptation mechanism that reduces hearing sensitivity as sustained sound levels increase . In the Reissner's membrane, a two‐cell‐thick partition separates the endolymphatic (high K + , low Na + ) and perilymphatic (high Na + , low K + ) fluid compartments .…”