Sleep Deprivation Modifies Noise-Induced Cochlear Injury Related to the Stress Hormone and Autophagy in Female Mice

Abstract

A lack of sleep is linked with a range of inner ear diseases, including hearing loss and tinnitus. Here, we used a mouse model to investigate the effects of sleep deprivation (SD) on noise vulnerability, and explored the mechanisms that might be involved in vitro, focusing particularly corticosterone levels and autophagic flux in cells. Female BALB/c mice were divided into six groups [control, acoustic trauma (AT)-alone, 1 day (d) SD-alone, 1d SD pre-AT, 5d SD-alone, and 5d SD pre-AT]. Cochlear damage was then assessed by analyzing auditory brainstem response (ABR), and by counting outer hair cells (OHCs) and the synaptic ribbons of inner hair cells (IHCs). In addition, we measured levels of serum corticosterone and autophagy protein expression in the basilar membranes by ELISA kits, and western blotting, respectively. We found that SD-alone temporarily elevated ABR wave I amplitude, but had no permanent effect on hearing level or IHC ribbon numbers. Combined with AT, the number of synaptic ribbons in the 1d SD pre-AT group was significantly higher than that in the AT-alone group, whereas the 5d SD pre-AT group showed more severe synaptopathy, and a greater loss of OHCs after 2 weeks than the other experimental groups exposed to noise. Correspondingly, the levels of corticosterone in the AT-alone group were higher than those of the 1d SD pre-AT group, but lower than those of the 5d SD pre-AT group. The 1d SD pre-AT group showed a marked elevation in the expression of microtubule-associated protein 1 light chain 3B (LC3B), whereas the AT-alone group exhibited only a mild increase. In contrast, the levels of LC3B did not change in the 5d SD pre-AT group. Experiments with HEI-OC-1 cells and cochlear basilar membrane cultures showed that high-concentrations of dexamethasone, and the inhibition of autophagy, aggravated cellular apoptosis induced by oxidative stress. In conclusion, noise-induced synaptopathy and hair cell loss can be mitigated by preceding 1d SD, but will be aggravated by preceding 5d SD. These findings may be attributable to corticosterone levels and the extent of autophagy.

Reporting Data on Auditory Brainstem Responses (ABR) in Rats: Recommendations Based on Review of Experimental Protocols and Literature

“…Female Balb/C mice subjected to sleep deprivation for both one day and segmental five days (sleep deprivation for 22 h and two-hour sleep-free) demonstrated a temporary increase in the amplitude of ABR wave I, but not in the thresholds. The amplitude returned to the baseline level two weeks later [ 34 ]. Male Wistar rats subjected to sleep deprivation for nine days had higher hearing thresholds at 8, 16, and 32 kHz, but not at low frequencies (2–4 kHz).…”

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions

“…Autophagy, as a recently found endogenous self-defense mechanism, degrades damaged organelles by lysosome to maintain internal homeostasis and preserve energy providing for cell survival upon stress like nutrient deficiency, pathogen infection, protein misfolding, and oxidative stress [76][77][78][79][80]. Previous studies [81,82] have shown that autophagy is upregulated in auditory hair cells after 3 Neural Plasticity intense noise exposure. The immunostaining results show the upregulation of LC3b, the indispensable component of autophagosome, and the colocalization of LC3b and Lamp1, indicating the enhanced fusion of autophagosome and lysosome.…”

Autophagy: A Novel Horizon for Hair Cell Protection

“…However, the autophagy induced by short-term SD causes a protective effect on HCs in the apoptotic processes induced by oxidative stress. Thus, it is demonstrated that short-term 3 Neural Plasticity SD exerts protective effects on HCs by regulating corticosterone and activating autophagy after noise exposure [95].…”

“…The presence of corticosterone receptors in the auditory system has been demonstrated in many studies [ 91 , 92 ], and it has been proved that high levels of corticosterone protect cochlear OHCs from various insults [ 93 , 94 ]. Recently, the effects of SD on noise vulnerability were investigated with respect to the potential underlying mechanisms [ 95 ]. According to the study, the elevated expression of LC3B and autophagy activation is observed in the short-term SD+ acoustic trauma (AT) group, whereas repeated SD+AT group could not exert a similar effect.…”