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

Mao, Huanyu; Chen, Yan

doi:10.1155/2021/4784385

Cited by 30 publications

(20 citation statements)

References 210 publications

(236 reference statements)

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“…Given that both PCB and noise exposure are associated with high levels of oxidative stress (Spreng, 2000; Samson et al, 2008; Bavithra et al, 2012; Lee et al, 2012; Selvakumar et al, 2012; Daiber et al, 2020; Mao and Chen, 2021; McCann et al, 2021), it was important to examine the capacity of the animals developmentally exposed to PCBs and/or noise in adulthood to mitigate oxidative stress. Therefore, the brains of the animals across different exposures were isolated at different time points (three months of age after the last ABR measurement which was post-noise-day 7 and seven months of age after the two-photon imaging).…”

Section: Resultsmentioning

confidence: 99%

Developmental exposure to polychlorinated biphenyls prevents recovery from noise-induced hearing loss and disrupts the functional organization of the inferior colliculus

Ibrahim

Louie

Shinagawa

et al. 2023

Preprint

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Exposure to combinations of environmental toxins is growing in prevalence, and therefore understanding their interactions is of increasing societal importance. Here, we examined the mechanisms by which two environmental toxins, polychlorinated biphenyls (PCBs) and high-amplitude acoustic noise, interact to produce dysfunction in central auditory processing. PCBs are well-established to impose negative developmental impacts on hearing. However, it is not known if developmental exposure to this ototoxin alters the sensitivity to other ototoxic exposures later in life. Here, male mice were exposed to PCBs in utero, and later as adults were exposed to 45 minutes of high-intensity noise. We then examined the impacts of the two exposures on hearing and the organization of the auditory midbrain using two-photon imaging and analysis of the expression of mediators of oxidative stress. We observed that developmental exposure to PCBs blocked hearing recovery from acoustic trauma. In vivo two-photon imaging of the inferior colliculus revealed that this lack of recovery was associated with disruption of the tonotopic organization and reduction of inhibition in the auditory midbrain. In addition, expression analysis in the inferior colliculus revealed that reduced GABAergic inhibition was more prominent in animals with a lower capacity to mitigate oxidative stress. These data suggest that combined PCBs and noise exposure act nonlinearly to damage hearing and that this damage is associated with synaptic reorganization, and reduced capacity to limit oxidative stress. In addition, this work provides a new paradigm by which to understand nonlinear interactions between combinations of environmental toxins.

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Section: Resultsmentioning

confidence: 99%

Developmental exposure to polychlorinated biphenyls prevents recovery from noise-induced hearing loss and disrupts the functional organization of the inferior colliculus

Ibrahim

Louie

Shinagawa

et al. 2023

Preprint

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“…Hair cells cannot regenerate in mammals, so loss of hair cells causes a permanent threshold shift (PTS) [15]. Although the detailed mechanism of noiseinduced hair cell loss is still unclear because of its complexity, it is well accepted that metabolic damage, including oxidative stress damage, Ca 2+ overload, and immune and inflammatory damage, are involved [9,10,[16][17][18]. Upon exposure to loud noise, metabolism occurs at a very high level in the cochlea, resulting in the consumption of a large amount of energy and the production of reactive oxygen species (ROS) [12,19,20].…”

Section: Introductionmentioning

confidence: 99%

Treatment with the Ferroptosis Inhibitor Ferrostatin-1 Attenuates Noise-Induced Hearing Loss by Suppressing Ferroptosis and Apoptosis

Wang

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Hair cell death induced by excessive reactive oxygen species (ROS) has been identified as the major pathogenesis of noise-induced hearing loss (NIHL). Recent studies have demonstrated that cisplatin- and neomycin-induced ototoxicity can be alleviated by ferroptosis inhibitors. However, whether ferroptosis inhibitors have a protective effect against NIHL remains unknown. We investigated the protective effect of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on NIHL in vivo in CBA/J mice and investigated the protective effect of Fer-1 on tert-butyl hydroperoxide (TBHP)-induced hair cell damage in vitro in cochlear explants and HEI-OC1 cells. We observed ROS overload and lipid peroxidation, which led to outer hair cell (OHC) apoptosis and ferroptosis, in the mouse cochlea after noise exposure. The expression level of apoptosis-inducing factor mitochondria-associated 2 (AIFM2) was substantially increased following elevation of the expression of its upstream protein P53 after noise exposure. The ferroptosis inhibitor Fer-1was demonstrated to enter the inner ear after the systemic administration. Administration of Fer-1 significantly alleviated noise-induced auditory threshold elevation and reduced the loss of OHCs, inner hair cell (IHC) ribbon synapses, and auditory nerve fibers (ANFs) caused by noise. Mechanistically, Fer-1 significantly reduced noise- and TBHP-induced lipid peroxidation and iron accumulation in hair cells, alleviating ferroptosis in cochlear cells consequently. Furthermore, Fer-1 treatment decreased the levels of TfR1, P53, and AIFM2. These results suggest that Fer-1 exerted its protective effects by scavenging of ROS and inhibition of TfR1-mediated ferroptosis and P53-AIFM2 signaling pathway-mediated apoptosis. Our findings suggest that Fer-1 is a promising drug for treating NIHL because of its ability to inhibit noise-induced hair cell apoptosis and ferroptosis, opening new avenues for the treatment of NIHL.

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“…At present, the recognized mechanisms are mechanical damage to the cochlea, metabolic damage, immune and inflammatory damage, and genetics (Ding et al 2019). Current studies have found that the genes involved in noise-induced hearing loss are associated with oxidative stress, DNA repair, gap junctions, apoptosis, K + recycling, and heat shock proteins (Ding et al 2019; Mao and plasticity 2021; Sliwinska-Kowalska and research 2013). It is well known that susceptibility to noise varies significantly among individuals, and not everyone experiences the same hearing loss after the same noise exposure (Sliwinska-Kowalska and research 2013).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Variant Analysis of Noise Susceptibility in C57BL/6J Mice

Wang¹,

Wang²,

Cai³

et al. 2022

Preprint

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Background: Susceptibility to noise varies dramatically between mice of the same genetic background; however, the underlying molecular mechanism remains unknown. Methods: C57BL/6J (B6) mice of the same sex, age, and strain were exposed to noise of the same intensity and duration, and the auditory brainstem response (ABR) threshold was determined 48 h later. Some mice had significant hearing loss, while some did not; the ABR threshold measured in these two groups of mice was significantly different. The cochlea of the two groups of mice was dissected, and RNA sequencing and analysis were performed. Differentially expressed genes (DEGs) between the two groups were selected, Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed, and proteinprotein interaction network maps were listed. Results: This study showed that noise exposure of the same intensity and duration caused different degrees of hearing loss in C57BL/6J (B6) mice. This was the result of the up-regulation or down-regulation of many genes, such as Nop2, Bysl, Rrp9, Spsb1, Fbxl20, and Fbxo31. Changes in the transcriptome of these genes may affect cochlear susceptibility to noise. Conclusion: The DEGs identified in this experiment may provide more insight into protocols for gene therapy in the clinical practice of hearing loss.

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

Cited by 30 publications

References 210 publications

Developmental exposure to polychlorinated biphenyls prevents recovery from noise-induced hearing loss and disrupts the functional organization of the inferior colliculus

Developmental exposure to polychlorinated biphenyls prevents recovery from noise-induced hearing loss and disrupts the functional organization of the inferior colliculus

Treatment with the Ferroptosis Inhibitor Ferrostatin-1 Attenuates Noise-Induced Hearing Loss by Suppressing Ferroptosis and Apoptosis

Transcriptome Variant Analysis of Noise Susceptibility in C57BL/6J Mice

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