Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue

Abstract

Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 hrs post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five “normal” ears, aged 54 to 89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear.

De novo mutation inELOVL1causes ichthyosis,acanthosis nigricans, hypomyelination, spastic paraplegia, high frequency deafness and optic atrophy

“…The patients' audiograms (figure 2I) with high frequency hearing loss resemble those of sensory presbycusis, caused by degeneration of the distal-most segments of the auditory neurons or their synaptic contacts 30. Not much is known about VLCFA requirements for inner ear development and function.…”

Stress is irrelevant to the onset and exacerbation of sensorineural hearing loss: Evaluation using various types of stress models in mice

“…In noiseexposed humans and animals, acoustic trauma (noise-induced hearing loss) leads to hair cell damage and causes a threshold shift [19,20]. Recent studies have indicated that ageing and/or moderate noise exposure can result in hidden hearing loss [21][22][23], which causes difficulties in speech discrimination and temporal processing in a noisy environment [24]. It can be detected physiologically, and is characterized by reduced amplitude in the sound-evoked spiral ganglion neuron activity (the first peak of the ABR waveform) [25][26][27].…”

Biomarkers for Hearing Dysfunction: Facts and Outlook

“…2 ). In humans, the absolute latencies and supra-threshold amplitudes of waves, ABR wave I (distal peripheral portion of the AN [90] ), ABR wave III (fibers from cochlear nucleus to caudal auditory pons and superior olivary complex [91] ), ABR wave VI (medial geniculate body or the auditory thalamus), or ARB wave V (believed to correspond with the IC in the midbrain [92,93] ) can be analyzed for various stimulus intensity levels and, for example, recording time of ABR measurements that should be set at >10 ms. An increasing body of evidence demonstrates that, due to altered leisure behavior and demographic crisis, the hidden hearing loss and auditory neuropathy are likely widely prevalent over time [94][95][96] , contributing to presbycusis [62,64,97] or hyperacusis and tinnitus [21,22,98] .…”