Involvement of the SIRT1/PGC-1α Signaling Pathway in Noise-Induced Hidden Hearing Loss

Abstract

Objective: To establish an animal model of noise-induced hidden hearing loss (NIHHL), evaluate the dynamic changes in cochlear ribbon synapses and cochlear hair cell morphology, and observe the involvement of the SIRT1/PGC-1α signaling pathway in NIHHL.Methods: Male guinea pigs were randomly divided into three groups: control group, noise exposure group, and resveratrol treatment group. Each group was divided into five subgroups: the control group and 1 day, 1 week, 2 weeks, and 1 month post noise exposure groups. The experimental groups received noise stimulation at 105 dB SPL for 2 h. Hearing levels were examined by auditory brainstem response (ABR). Ribbon synapses were evaluated by inner ear basilar membrane preparation and immunofluorescence. The cochlear morphology was observed using scanning electron microscopy. Western blotting analysis and immunofluorescence was performed to assess the change of SIRT1/PGC-1α signaling. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), ATP and SIRT1 activity were measured using commercial testing kits.Results: In the noise exposure group, hearing threshold exhibited a temporary threshold shift (TTS), and amplitude of ABR wave I decreased irreversibly. Ribbon synapse density decreased after noise exposure, and the stereocilia were chaotic and then returned to normal. The expression and activity of SIRT1 and PGC-1α protein was lower than that in the control group. SOD, CAT and ATP were also influenced by noise exposure and were lower than those in the control group, but MDA showed no statistical differences compared with the control group. After resveratrol treatment, SIRT1 expression and activity showed a significant increase after noise exposure, compared with the noise exposure group. In parallel, the PGC-1α and antioxidant proteins were also significantly altered after noise exposure, compared with the noise exposure group. The damage to the ribbon synapses and the stereocilia were attenuated by resveratrol as well. More importantly, the auditory function, especially ABR wave I amplitudes, was also promoted in the resveratrol treatment group.Conclusion: The SIRT1/PGC-1α signaling pathway and oxidative stress are involved in the pathogenesis of NIHHL and could be potential therapeutical targets in the future.

Resveratrol prevents hearing loss and a subregion specific- reduction of serotonin reuptake transporter induced by noise exposure in the central auditory system

“…Several lines of evidence have shown that RSV can alleviate hearing loss induced by noise exposure and prevent the loss of SERT induced by noise exposure (Seidman et al, 2003;Li et al, 2019). In the current study, we examined the effects of RSV on hearing loss and loss of SERT induced by noise exposure, and found that RSV provide protection against noise-induced hearing loss and SERT loss in DCN, ICd, and Au1 layers I-IV subregions, which was consistent with previous reports (Li et al, 2019;Liu et al, 2022). Based on a previous study (Shih et al, 2016), we speculate that RSV may have the potential to protect against noise exposure-induced SERT loss, possibly through binding to SERT.…”

“…Resveratrol (3, 5, 4 -trihydroxystilbene, RSV) is a naturally occurring compound with a variety of pharmacological properties, including anti-inflammatory, antioxidant, and neuroprotective effects (Soleas et al, 1997;Hao and He, 2004;Sonmez et al, 2007). Recent studies have suggested that RSV can alleviate noise exposure-induced or age-related hearing loss in mice (Pang et al, 2019;Liu et al, 2022). One of the potential mechanisms by which RSV alleviate hearing loss is protecting against noise exposureinduced hair cells damage or loss (Seidman et al, 2003;Hanci et al, 2016).…”

Potential therapeutic role of SIRT1 in age- related hearing loss

“…At present, there are many studies on cisplatin-induced hearing loss and noiseinduced deafness. The protective effect of SIRT1 in cisplatininduced hearing loss and noise-induced deafness confirms the potential therapeutic role of SIRT1 in the cochlea (Pang et al, 2018;Zhan et al, 2021;Liu et al, 2022). To obtain the cytotoxic or cytoprotective effect of a certain treatment on hearing in a short time, experiments in vitro are preferred.…”

Approaches to Mitigate Mitochondrial Dysfunction in Sensorineural Hearing Loss

“…PGC-1a protein levels are shown to decline after noise exposure. 47 PGC-1a overexpression, on the other hand, induced the NRF-1 and TFAM levels and reduced the cellular senescence and apoptosis in a rat cochlear marginal cell senescence model harboring mtDNA4834 deletion. 88 In accord with this, Zhang et al showed that the expression of PGC1a, NRF1, NRF2, and TFAM decreased in mouse immortalized cochlear cells (HEI-OC1) following exposure to cisplatin, causing impairment in mitochondrial biogenesis.…”