Abstract
Moderate acoustic overexposure in adult rodents is known to cause acute loss of synapses on sensory inner hair cells (IHCs) and delayed degeneration of the auditory nerve, despite the completely reversible temporary threshold shift (TTS) and morphologically intact hair cells. Our objective was to determine whether a cochlear synaptopathy followed by neuropathy occurs after noise exposure in pubescence, and to define neuropathic versus non-neuropathic noise levels for pubescent mice. While exposing 6 week old CBA/CaJ mice to 8-16 kHz bandpass noise for 2 hrs, we defined 97 dB sound pressure level (SPL) as the threshold for this particular type of neuropathic exposure associated with TTS, and 94 dB SPL as the highest non-neuropathic noise level associated with TTS. Exposure to 100 dB SPL caused permanent threshold shift although exposure of 16 week old mice to the same noise is reported to cause only TTS. Amplitude of wave I of the auditory brainstem response, which reflects the summed activity of the cochlear nerve, was complemented by synaptic ribbon counts in IHCs using confocal microscopy, and by stereological counts of peripheral axons and cell bodies of the cochlear nerve from 24 hours to 16 months post exposure. Mice exposed to neuropathic noise demonstrated immediate cochlear synaptopathy by 24 hours post exposure, and delayed neurodegeneration characterized by axonal retraction at 8 months, and spiral ganglion cell loss at 8-16 months post exposure. Although the damage was initially limited to the cochlear base, it progressed to also involve the cochlear apex by 8 months post exposure. Our data demonstrate a fine line between neuropathic and non-neuropathic noise levels associated with TTS in the pubescent cochlea.
Highlights
Noise-induced hearing loss is a growing epidemic worldwide, with over 1.6 million new cases yearly [1]
Since primary cochlear neuropathy has far been carefully studied only after noise exposure in young adulthood, we explored this phenomenon after noise exposure in pubescence [9], because the peri-pubescent cochlea is known to have enhanced sensitivity to permanent threshold shift (PTS) in various animal models [10,11,12,13,14,15,16], and hearing loss is predicted to rise in juveniles [17]
We used a combination of sound-evoked responses from the auditory nerve and outer hair cells to infer cochlear synaptopathy in 6 week old pubescent mice (Figs 1 and 2)
Summary
Noise-induced hearing loss is a growing epidemic worldwide, with over 1.6 million new cases yearly [1]. Recent research in mice and guinea pigs has shown that even exposure to moderate noise levels, previously thought to cause only temporary hearing loss, can result in immediate and irreversible loss of cochlear neurons [2,3]. High noise levels cause permanent threshold shift (PTS), as assessed using behavioral threshold audiometry or physiologic metrics in both animals and humans. The common physiological metrics are auditory brainstem evoked responses (ABRs) and otoacoustic emissions (OAEs). PTS is seen in permanent elevation of both ABR and OAE thresholds, with multiple structural correlates within the cochlea: loss of hair cells or their stereocilia, collapse of the organ of Corti, loss of cochlear neurons from the spiral ganglion, loss of fibrocytes within the spiral ligament, and atrophy of the stria vascularis [4,5,6]
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