Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss

Abstract

Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells

“…In the mammalian cochlea, outside of the extreme apex, 495% of cochlear nerve fibres are unbranched, contacting a single IHC via a single terminal swelling, with a single active zone at which a single presynaptic ribbon is tethered to the IHC membrane 21 . Thus, ribbon quantifications provide an accurate metric of the IHC afferent innervation 22 . It has to be pointed out that CtBP2 þ ribbons are not systematically coupled to NF-H þ staining, because neurofilaments do not fill terminal axon swellings 22 .…”

“…Thus, ribbon quantifications provide an accurate metric of the IHC afferent innervation 22 . It has to be pointed out that CtBP2 þ ribbons are not systematically coupled to NF-H þ staining, because neurofilaments do not fill terminal axon swellings 22 . Consistent with the finding that some type I SGNs aberrantly project to the OHC region in ephrin-A5 À / À mice, mean counts revealed a significant decrease of presynaptic active zones per IHC in ephrin-A5 À / À compared with WT mice (Fig.…”

Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice

“…4,6,63 This is interesting because the damage to the dendrites of SGNs, and even the death of SGNs, were seen in regions of the cochlea where there was no significant HC loss and limited or no functional hearing loss. However, more experiments are needed to see if this lesion can occur in other species that possess bigger cochleae and therefore have a longer distance between the IHC-SGN synapses and the soma of SGNs.…”

“…2 Although OHC loss is a contributing factor to NIHL, hearing deficits are not closely correlated with the number of missing OHCs, suggesting that the death of other cell types in the cochlea has an important role in the development of NIHL. [3][4][5] For example, loss of spiral ganglion neurons (SGNs) 6 and cell death in structures outside the OC such as the stria vascularis may also contribute to NIHL. [7][8][9][10][11] Both necrosis and apoptosis have been implicated in NIHL.…”

Activation of TRAIL‐DR5 pathway promotes sensorineural degeneration in the inner ear

“…As SGN degeneration is typically slow in vivo (Kujawa & Liberman, 2009), we studied it in an accelerated model in vitro , using a mouse auditory neuroblast cell line, VOT‐33 (Lawoko‐Kerali et al ., 2004). TRAIL did not induce apoptosis in VOT‐33 cells, as assessed using the TUNEL assays (Fig.…”