scholarly journals Constant Light Dysregulates Cochlear Circadian Clock and Exacerbates Noise-Induced Hearing Loss

2020 ◽  
Vol 21 (20) ◽  
pp. 7535
Author(s):  
Chao-Hui Yang ◽  
Chung-Feng Hwang ◽  
Jiin-Haur Chuang ◽  
Wei-Shiung Lian ◽  
Feng-Sheng Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Circadian Clock ◽  
Auditory System ◽  
High Intensity ◽  
Noise Exposure ◽  
Clock Genes ◽  
Outer Hair Cells ◽  
Constant Light ◽  
Noise Induced Hearing Loss ◽  
Brainstem Response

Noise-induced hearing loss is one of the major causes of acquired sensorineural hearing loss in modern society. While people with excessive exposure to noise are frequently the population with a lifestyle of irregular circadian rhythms, the effects of circadian dysregulation on the auditory system are still little known. Here, we disturbed the circadian clock in the cochlea of male CBA/CaJ mice by constant light (LL) or constant dark. LL significantly repressed circadian rhythmicity of circadian clock genes Per1, Per2, Rev-erbα, Bmal1, and Clock in the cochlea, whereas the auditory brainstem response thresholds were unaffected. After exposure to low-intensity (92 dB) noise, mice under LL condition initially showed similar temporary threshold shifts to mice under normal light–dark cycle, and mice under both conditions returned to normal thresholds after 3 weeks. However, LL augmented high-intensity (106 dB) noise-induced permanent threshold shifts, particularly at 32 kHz. The loss of outer hair cells (OHCs) and the reduction of synaptic ribbons were also higher in mice under LL after noise exposure. Additionally, LL enhanced high-intensity noise-induced 4-hydroxynonenal in the OHCs. Our findings convey new insight into the deleterious effect of an irregular biological clock on the auditory system.

scholarly journals Inhibition of Cochlear HMGB1 Expression Attenuates Oxidative Stress and Inflammation in an Experimental Murine Model of Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 810
Author(s):  
Cheng-Ping Shih ◽  
Chao-Yin Kuo ◽  
Yuan-Yung Lin ◽  
Yi-Chun Lin ◽  
Hang-Kang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Outer Hair Cells ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Post Exposure ◽  
Nadph Oxidase 4 ◽  
Brainstem Response ◽  
Ros Formation

Noise-induced hearing loss (NIHL) is a common inner ear disease but has complex pathological mechanisms, one of which is increased oxidative stress in the cochlea. The high-mobility group box 1 (HMGB1) protein acts as an inflammatory mediator and shows different activities with redox modifications linked to the generation of reactive oxygen species (ROS). We aimed to investigate whether manipulation of cochlear HMGB1 during noise exposure could prevent noise-induced oxidative stress and hearing loss. Sixty CBA/CaJ mice were divided into two groups. An intraperitoneal injection of anti-HMGB1 antibodies was administered to the experimental group; the control group was injected with saline. Thirty minutes later, all mice were subjected to white noise exposure. Subsequent cochlear damage, including auditory threshold shifts, hair cell loss, expression of cochlear HMGB1, and free radical activity, was then evaluated. The levels of HMGB1 and 4-hydroxynonenal (4-HNE), as respective markers of reactive nitrogen species (RNS) and ROS formation, showed slight increases on post-exposure day 1 and achieved their highest levels on post-exposure day 4. After noise exposure, the antibody-treated mice showed markedly less ROS formation and lower expression of NADPH oxidase 4 (NOX4), nitrotyrosine, inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM‑1) than the saline-treated control mice. A significant amelioration was also observed in the threshold shifts of the auditory brainstem response and the loss of outer hair cells in the antibody-treated versus the saline-treated mice. Our results suggest that inhibition of HMGB1 by neutralization with anti-HMGB1 antibodies prior to noise exposure effectively attenuated oxidative stress and subsequent inflammation. This procedure could therefore have potential as a therapy for NIHL.

scholarly journals Effect of Phlorofucofuroeckol A and Dieckol Extracted from Ecklonia cava on Noise-induced Hearing Loss in a Mouse Model

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 443
Author(s):  
Hyunjun Woo ◽  
Min-Kyung Kim ◽  
Sohyeon Park ◽  
Seung-Hee Han ◽  
Hyeon-Cheol Shin ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Radical Scavenging ◽  
Threshold Shift ◽  
Ecklonia Cava ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Antioxidant Agents ◽  
Brainstem Response

One of the well-known causes of hearing loss is noise. Approximately 31.1% of Americans between the ages of 20 and 69 years (61.1 million people) have high-frequency hearing loss associated with noise exposure. In addition, recurrent noise exposure can accelerate age-related hearing loss. Phlorofucofuroeckol A (PFF-A) and dieckol, polyphenols extracted from the brown alga Ecklonia cava, are potent antioxidant agents. In this study, we investigated the effect of PFF-A and dieckol on the consequences of noise exposure in mice. In 1,1-diphenyl-2-picrylhydrazyl assay, dieckol and PFF-A both showed significant radical-scavenging activity. The mice were exposed to 115 dB SPL of noise one single time for 2 h. Auditory brainstem response(ABR) threshold shifts 4 h after 4 kHz noise exposure in mice that received dieckol were significantly lower than those in the saline with noise group. The high-PFF-A group showed a lower threshold shift at click and 16 kHz 1 day after noise exposure than the control group. The high-PFF-A group also showed higher hair cell survival than in the control at 3 days after exposure in the apical turn. These results suggest that noise-induced hair cell damage in cochlear and the ABR threshold shift can be alleviated by dieckol and PFF-A in the mouse. Derivatives of these compounds may be applied to individuals who are inevitably exposed to noise, contributing to the prevention of noise-induced hearing loss with a low probability of adverse effects.

scholarly journals Ultrasound Microbubbles Enhance the Efficacy of Insulin-Like Growth Factor-1 Therapy for the Treatment of Noise-Induced Hearing Loss

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3626
Author(s):  
Yi-Chun Lin ◽  
Yuan-Yung Lin ◽  
Hsin-Chien Chen ◽  
Chao-Yin Kuo ◽  
Ai-Ho Liao ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Growth Factor ◽  
Inner Ear ◽  
Outer Hair Cells ◽  
Round Window Membrane ◽  
Insulin Like Growth Factor ◽  
Noise Induced Hearing Loss ◽  
Ear Diseases ◽  
Brainstem Response ◽  
Ultrasound Microbubbles

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.

scholarly journals Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Holly J. Beaulac ◽  
Felicia Gilels ◽  
Jingyuan Zhang ◽  
Sarah Jeoung ◽  
Patricia M. White
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multiphoton Microscopy ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Knock Out ◽  
Cell Death Pathway ◽  
Cochlear Damage

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/−), and Foxo3 knock-out (Foxo3−/−) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3−/− OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3−/− mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise-exposed Foxo3−/− mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

scholarly journals Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss

2021 ◽  
Vol 15 ◽  
Author(s):  
Anette Elisabeth Fransson ◽  
Pernilla Videhult Pierre ◽  
Mårten Risling ◽  
Göran Frans Emanuel Laurell
Keyword(s):  
Hearing Loss ◽  
Molecular Hydrogen ◽  
Noise Exposure ◽  
Real Life ◽  
Outer Hair Cells ◽  
Broadband Noise ◽  
Hydrogen Gas ◽  
Rescue Treatment ◽  
Brainstem Response ◽  
Antioxidant Effects

Noise exposure is the most important external factor causing acquired hearing loss in humans, and it is strongly associated with the production of reactive oxygen species (ROS) in the cochlea. Several studies reported that the administration of various compounds with antioxidant effects can treat oxidative stress-induced hearing loss. However, traditional systemic drug administration to the human inner ear is problematic and has not been successful in a clinical setting. Thus, there is an urgent need to develop rescue treatment for patients with acute acoustic injuries. Hydrogen gas has antioxidant effects, rapid distribution, and distributes systemically after inhalation.The purpose of this study was to determine the protective efficacy of a single dose of molecular hydrogen (H2) on cochlear structures. Guinea pigs were divided into six groups and sacrificed immediately after or at 1 or 2 weeks. The animals were exposed to broadband noise for 2 h directly followed by 1-h inhalation of 2% H2 or room air. Electrophysiological hearing thresholds using frequency-specific auditory brainstem response (ABR) were measured prior to noise exposure and before sacrifice. ABR thresholds were significantly lower in H2-treated animals at 2 weeks after exposure, with significant preservation of outer hair cells in the entire cochlea. Quantification of synaptophysin immunoreactivity revealed that H2 inhalation protected the cochlear inner hair cell synaptic structures containing synaptophysin. The inflammatory response was greater in the stria vascularis, showing increased Iba1 due to H2 inhalation.Repeated administration of H2 inhalation may further improve the therapeutic effect. This animal model does not reproduce conditions in humans, highlighting the need for additional real-life studies in humans.

scholarly journals Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss

2021 ◽  
Vol 9 ◽  
Author(s):  
Zu-Hong He ◽  
Song Pan ◽  
Hong-Wei Zheng ◽  
Qiao-Jun Fang ◽  
Kayla Hill ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Calcineurin Inhibitor ◽  
Noise Exposure ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Oxygen Species ◽  
Noise Induced Hearing Loss ◽  
Activated T Cells ◽  
Interfering Rna

Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Here we showed that CaN immunolabeling in outer hair cells (OHCs) and nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) in OHC nuclei are significantly increased after moderate noise exposure in adult CBA/J mice. Consequently, treatment with FK506 significantly reduces moderate-noise-induced loss of OHCs and NIHL. Furthermore, induction of reactive oxygen species (ROS) by moderate noise was significantly diminished by treatment with FK506. In agreement with our previous finding that autophagy marker microtubule-associated protein light chain 3B (LC3B) does not change in OHCs under conditions of moderate-noise-induced permanent threshold shifts, treatment with FK506 increases LC3B immunolabeling in OHCs after exposure to moderate noise. Additionally, prevention of NIHL by treatment with FK506 was partially abolished by pretreatment with LC3B small interfering RNA. Taken together, these results indicate that attenuation of moderate-noise-induced OHC loss and hearing loss by FK506 treatment occurs not only via inhibition of CaN activity but also through inhibition of ROS and activation of autophagy.

scholarly journals Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss

2019 ◽  
Vol 16 (18) ◽  
pp. 3428 ◽  
Author(s):  
Sang Hyun Kwak ◽  
Gi-Sung Nam ◽  
Seong Hoon Bae ◽  
Jinsei Jung
Keyword(s):  
Hearing Loss ◽  
Retinoic Acid ◽  
Noise Exposure ◽  
Retinoic Acid Receptor ◽  
Protective Effects ◽  
Noise Induced Hearing Loss ◽  
Acid Receptor ◽  
Significant Difference ◽  
Brainstem Response ◽  
Selective Agonists

Noise is one of the most common causes of hearing loss in industrial countries. There are many studies about chemical agents to prevent noise-induced hearing loss (NIHL). However, there is no commercially available drug yet. Retinoic acid is an active metabolite of Vitamin A; it has an anti-apoptic role in NIHL. This study aims to verify the differences among selective agonists of retinoic acid receptors (RARs) in NIHL. All-trans retinoic acid (ATRA), AM80 (selective retinoic acid receptor α agonist), AC261066 (Selective retinoic acid receptor β1 agonist), and CD1530 (Selective retinoic acid λ agonist) were injected to 6–7 weeks old CJ5BL/6 mice before noise (110 dB for 3 h) exposure. In the auditory brainstem response test pre-, post 1, 3, and 7 days after noise exposure, not only ATRA but all kinds of selective RAR agonists showed protective effects in hearing threshold and wave I amplitude. Though there was no significant difference in the level of protective effects between agonists, α agonist showed the most prominent effect in preserving hearing function as well as outer hair cells after noise exposure. In conclusion, selective agonists of RAR demonstrate comparable protective effects against NIHL to retinoic acid. Given that these selective RAR agonists have less side effects than retinoic acid, they may be promising potential drugs against NIHL.

scholarly journals Effects of D-methionine in mice with noise-induced hearing loss mice

2019 ◽  
Vol 47 (8) ◽  
pp. 3874-3885 ◽  
Author(s):  
Yanru Wang ◽  
Yan Qu ◽  
Xuzhen Chen ◽  
Pu Zhang ◽  
Dan Su ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Basement Membrane ◽  
Mouse Model ◽  
Hair Cells ◽  
Noise Exposure ◽  
Stria Vascularis ◽  
Connexin 26 ◽  
Noise Induced Hearing Loss ◽  
Expression Levels ◽  
Brainstem Response

Objective To study the effects of D-methionine in a mouse model of noise-induced hearing loss (NIHL). Methods We investigated changes in auditory function and microscopic cochlear structure in a mouse model of NIHL, and carried out 4-hydroxynonenal (4-HNE) immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling, and examined expression levels of connexins 26 and 30 by western blot. Results The auditory brainstem response threshold was significantly increased by noise exposure. Noise exposure also damaged the inner and particularly the outer hair cells in the cochlear basement membrane, while histochemistry demonstrated only scattered loss of hair cells in the basement membrane in mice treated with D-methionine before or after noise exposure. D-methionine inhibited apoptosis in the cochlear basement membrane, stria vascularis, and spiral ligament. 4-HNE expression in the basement membrane, stria vascularis, and spiral collateral ligament was increased by noise exposure, but this increase was attenuated by D-methionine. Connexin 26 and connexin 30 expression levels were reduced by noise exposure, and this effect was similarly attenuated by D-methionine administered either before or after noise exposure. Conclusion D-methionine administered before or after noise exposure could rescue NIHL by protecting cochlear morphology, inhibiting apoptosis, and maintaining connexin 26 and 30 expression.

scholarly journals The Physiological Bases of Hidden Noise-Induced Hearing Loss: Protocol for a Functional Neuroimaging Study (Preprint)

2017 ◽  
Author(s):  
Rebecca Susan Dewey ◽  
Deborah A Hall ◽  
Hannah Guest ◽  
Garreth Prendergast ◽  
Christopher J Plack ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Functional Neuroimaging ◽  
Nerve Fibers ◽  
High Threshold ◽  
Hearing Level ◽  
Noise Induced Hearing Loss ◽  
Brainstem Response ◽  
Neuroimaging Study ◽  
Hidden Hearing Loss

BACKGROUND Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as hidden hearing loss have been confirmed in several rodent species, but the implications for human hearing are unclear. OBJECTIVE Our Medical Research Council–funded program aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure. Behavioral and neuroimaging techniques are being used in a series of parallel studies aimed at detecting hidden hearing loss in humans. The planned neuroimaging study aims to (1) identify central auditory biomarkers associated with hidden hearing loss; (2) investigate whether there are any additive contributions from tinnitus or diminished sound tolerance, which are often comorbid with hearing problems; and (3) explore the relation between subcortical functional magnetic resonance imaging (fMRI) measures and the auditory brainstem response (ABR). METHODS Individuals aged 25 to 40 years with pure tone hearing thresholds ≤20 dB hearing level over the range 500 Hz to 8 kHz and no contraindications for MRI or signs of ear disease will be recruited into the study. Lifetime noise exposure will be estimated using an in-depth structured interview. Auditory responses throughout the central auditory system will be recorded using ABR and fMRI. Analyses will focus predominantly on correlations between lifetime noise exposure and auditory response characteristics. RESULTS This paper reports the study protocol. The funding was awarded in July 2013. Enrollment for the study described in this protocol commenced in February 2017 and was completed in December 2017. Results are expected in 2018. CONCLUSIONS This challenging and comprehensive study will have the potential to impact diagnostic procedures for hidden hearing loss, enabling early identification of noise-induced auditory damage via the detection of changes in central auditory processing. Consequently, this will generate the opportunity to give personalized advice regarding provision of ear defense and monitoring of further damage, thus reducing the incidence of noise-induced hearing loss.

scholarly journals Analysis of Chronic Tinnitus in Noise-Induced Hearing Loss and Presbycusis

2021 ◽  
Vol 10 (8) ◽  
pp. 1779
Author(s):  
Hee Jin Kang ◽  
Dae Woong Kang ◽  
Sung Su Kim ◽  
Tong In Oh ◽  
Sang Hoon Kim ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Otoacoustic Emissions ◽  
Pure Tone Audiometry ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Chronic Tinnitus ◽  
Noise Induced Hearing Loss ◽  
Distortion Product ◽  
Hearing Thresholds ◽  
Brainstem Response

The most frequent causes of tinnitus associated with hearing loss are noise-induced hearing loss and presbycusis. The mechanism of tinnitus is not yet clear, although several hypotheses have been suggested. Therefore, we aimed to analyze characteristics of chronic tinnitus between noise-induced hearing loss and presbycusis. Materials and Methods: This paper is a retrospective chart review and outpatient clinic-based study of 248 patients with chronic tinnitus from 2015 to 2020 with noise-induced or presbycusis. Pure tone audiometry (PTA), auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE), transient evoked otoacoustic emissions (TEOAE), and tinnitograms were conducted. Results: PTA showed that hearing thresholds at all frequencies were higher in patients with noise-induced hearing loss than the presbycusis group. ABR tests showed that patients with presbycusis had longer wave I and III latencies (p < 0.05 each) than patients with noise-induced hearing loss. TEOAE tests showed lower values in patients with noise-induced hearing loss than presbycusis at 1.5, 2, 3, and 4 kHz (p < 0.05 each). DPOAE tests showed that response rates in both ears at 1.5, 2, and 3 kHz were significantly higher in patients with presbycusis than noise-induced hearing loss (p < 0.05 each). Discussion: This study showed that hearing thresholds were higher, the loudness of tinnitus was smaller, and the degree of damage to outer hair cells was lower in patients with presbycusis than with noise-induced hearing loss. Moreover, wave I and III latencies were more prolonged in patients with presbycusis despite their having lower hearing thresholds. These phenomena may reflect the effects of aging or degeneration of the central nervous system with age. Further studies are needed to evaluate the etiologies of tinnitus.

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