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Nature Communications Jan 2024Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus... (Meta-Analysis)
Meta-Analysis
Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries. GWAS in 596,905 Million Veteran Program subjects identified 39 tinnitus loci, and identified genes related to neuronal synapses and cochlear structural support. Applying state-of-the-art analytic tools, we confirm a large number of shared variants, but also a distinct genetic architecture of tinnitus, with higher polygenicity and large proportion of variants not shared with hearing difficulty. Tissue-expression analysis for tinnitus infers broad enrichment across most brain tissues, in contrast to hearing difficulty. Finally, tinnitus is not only correlated with hearing loss, but also with a spectrum of psychiatric disorders, providing potential new avenues for treatment. This study establishes tinnitus as a distinct disorder separate from hearing difficulties.
Topics: Humans; Tinnitus; Cochlea; Deafness; Hearing Loss, Noise-Induced
PubMed: 38242899
DOI: 10.1038/s41467-024-44842-x -
International Journal of Molecular... Nov 2023Tinnitus is the perception of noise in the absence of acoustic stimulation (phantom noise). In most patients suffering from chronic peripheral tinnitus, an alteration of... (Review)
Review
Tinnitus is the perception of noise in the absence of acoustic stimulation (phantom noise). In most patients suffering from chronic peripheral tinnitus, an alteration of outer hair cells (OHC) starting from the stereocilia (SC) occurs. This is common following ototoxic drugs, sound-induced ototoxicity, and acoustic degeneration. In all these conditions, altered coupling between the tectorial membrane (TM) and OHC SC is described. The present review analyzes the complex interactions involving OHC and TM. These need to be clarified to understand which mechanisms may underlie the onset of tinnitus and why the neuropathology of chronic degenerative tinnitus is similar, independent of early triggers. In fact, the fine neuropathology of tinnitus features altered mechanisms of mechanic-electrical transduction (MET) at the level of OHC SC. The appropriate coupling between OHC SC and TM strongly depends on autophagy. The involvement of autophagy may encompass degenerative and genetic tinnitus, as well as ototoxic drugs and acoustic trauma. Defective autophagy explains mitochondrial alterations and altered protein handling within OHC and TM. This is relevant for developing novel treatments that stimulate autophagy without carrying the burden of severe side effects. Specific phytochemicals, such as curcumin and berberin, acting as autophagy activators, may mitigate the neuropathology of tinnitus.
Topics: Humans; Tinnitus; Hair Cells, Auditory, Outer; Stereocilia; Sound; Acoustic Stimulation
PubMed: 38068993
DOI: 10.3390/ijms242316664 -
Biomedicine & Pharmacotherapy =... Jul 2023No medical interventions for noise induced hearing loss (NIHL) are approved by the Food and Drug Administration (USA). Here, we evaluate statins in CBA/CaJ mice as...
No medical interventions for noise induced hearing loss (NIHL) are approved by the Food and Drug Administration (USA). Here, we evaluate statins in CBA/CaJ mice as potential drugs for hearing loss. Direct delivery of fluvastatin to the cochlea and oral delivery of lovastatin were evaluated. Baseline hearing was assessed using Auditory Brain Stem Responses (ABRs). For fluvastatin, a cochleostomy was surgically created in the basal turn of the cochlea by a novel, laser-based procedure, through which a catheter attached to a mini-osmotic pump was inserted. The pump was filled with a solution of 50 µM fluvastatin+carrier or with the carrier alone for continuous delivery to the cochlea. Mice were exposed to one octave band noise (8-16 kHz x 2 h x 110 dB SPL). In our past work with guinea pigs, fluvastatin protected in the contralateral cochlea. In this study in CBA/CaJ mice, hearing was also assessed in the contralateral cochlea 1-4 weeks after noise exposure. At two weeks post exposure, ABR thresholds at 4, 8, 12, 16, and 32 kHz were elevated, as expected, in the noise+carrier alone treated mice by approximately 9-, 17-, 41-, 29-, and 34-dB, respectively. Threshold elevations were smaller in mice treated with noise+fluvastatin to about 2-, 6-, 20-,12- and 12-dB respectively. Survival of inner hair cell synapses were not protected by fluvastatin over these frequencies. Lovastatin delivered by gavage showed lower threshold shifts than with carrier alone. These data show that direct and oral statin delivery protects mice against NIHL.
Topics: United States; Mice; Animals; Guinea Pigs; Mice, Inbred CBA; Hearing Loss, Noise-Induced; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Fluvastatin; Lovastatin; Excipients
PubMed: 37435721
DOI: 10.1016/j.biopha.2023.114674 -
Seminars in Hearing Nov 2023Noise-induced hearing loss (NIHL) continues to be a pervasive problem for the nation's workforce, particularly the nation's mining personnel. As one of the leading... (Review)
Review
Noise-induced hearing loss (NIHL) continues to be a pervasive problem for the nation's workforce, particularly the nation's mining personnel. As one of the leading health and safety organizations in the world, the National Institute for Occupational Health and Safety (NIOSH) in Pittsburgh maintains a Hearing Loss Prevention Program (HLPP) to conduct research to reduce NIHL loss among the nation's miners. This document provides a brief overview of this HLPP, describing some of the research techniques involved in the development of engineering noise controls, methods for the development of administrative noise controls, and some of the products available to the public to protect the nation's workers hearing.
PubMed: 37818149
DOI: 10.1055/s-0043-1769500 -
Trends in Hearing 2024Cochlear synaptopathy, a form of cochlear deafferentation, has been demonstrated in a number of animal species, including non-human primates. Both age and noise exposure... (Review)
Review
Cochlear synaptopathy, a form of cochlear deafferentation, has been demonstrated in a number of animal species, including non-human primates. Both age and noise exposure contribute to synaptopathy in animal models, indicating that it may be a common type of auditory dysfunction in humans. Temporal bone and auditory physiological data suggest that age and occupational/military noise exposure also lead to synaptopathy in humans. The predicted perceptual consequences of synaptopathy include tinnitus, hyperacusis, and difficulty with speech-in-noise perception. However, confirming the perceptual impacts of this form of cochlear deafferentation presents a particular challenge because synaptopathy can only be confirmed through post-mortem temporal bone analysis and auditory perception is difficult to evaluate in animals. Animal data suggest that deafferentation leads to increased central gain, signs of tinnitus and abnormal loudness perception, and deficits in temporal processing and signal-in-noise detection. If equivalent changes occur in humans following deafferentation, this would be expected to increase the likelihood of developing tinnitus, hyperacusis, and difficulty with speech-in-noise perception. Physiological data from humans is consistent with the hypothesis that deafferentation is associated with increased central gain and a greater likelihood of tinnitus perception, while human data on the relationship between deafferentation and hyperacusis is extremely limited. Many human studies have investigated the relationship between physiological correlates of deafferentation and difficulty with speech-in-noise perception, with mixed findings. A non-linear relationship between deafferentation and speech perception may have contributed to the mixed results. When differences in sample characteristics and study measurements are considered, the findings may be more consistent.
Topics: Humans; Cochlea; Tinnitus; Animals; Speech Perception; Hyperacusis; Noise; Auditory Perception; Synapses; Hearing Loss, Noise-Induced; Loudness Perception
PubMed: 38738337
DOI: 10.1177/23312165241239541 -
Nature Communications Jun 2023TRPA1 channels are expressed in nociceptive neurons, where they detect noxious stimuli, and in the mammalian cochlea, where their function is unknown. Here we show that...
TRPA1 channels are expressed in nociceptive neurons, where they detect noxious stimuli, and in the mammalian cochlea, where their function is unknown. Here we show that TRPA1 activation in the supporting non-sensory Hensen's cells of the mouse cochlea causes prolonged Ca responses, which propagate across the organ of Corti and cause long-lasting contractions of pillar and Deiters' cells. Caged Ca experiments demonstrated that, similar to Deiters' cells, pillar cells also possess Ca-dependent contractile machinery. TRPA1 channels are activated by endogenous products of oxidative stress and extracellular ATP. Since both these stimuli are present in vivo after acoustic trauma, TRPA1 activation after noise may affect cochlear sensitivity through supporting cell contractions. Consistently, TRPA1 deficiency results in larger but less prolonged noise-induced temporary shift of hearing thresholds, accompanied by permanent changes of latency of the auditory brainstem responses. We conclude that TRPA1 contributes to the regulation of cochlear sensitivity after acoustic trauma.
Topics: Animals; Mice; Cochlea; Epithelial Cells; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Noise-Induced; Labyrinth Supporting Cells; TRPA1 Cation Channel
PubMed: 37391431
DOI: 10.1038/s41467-023-39589-w -
Seminars in Hearing Nov 2023The National Institute for Occupational Safety and Health (NIOSH) evaluated continuous and impact noise exposures and hearing loss among workers at a hammer forge... (Review)
Review
The National Institute for Occupational Safety and Health (NIOSH) evaluated continuous and impact noise exposures and hearing loss among workers at a hammer forge company. Full-shift personal noise exposure measurements were collected on forge workers across 15 different job titles; impact noise characteristics and one-third octave band noise levels were assessed at the forge hammers; and 4,750 historic audiometric test records for 483 workers were evaluated for hearing loss trends. Nearly all workers' noise exposures exceeded regulatory and/or recommended exposure limits. Workers working in jobs at or near the hammers had full-shift time-weighted average noise exposures above 100 decibels, A-weighted. Impact noise at the hammers reached up to 148 decibels. Analysis of audiometric test records showed that 82% of workers had experienced a significant threshold shift, as defined by NIOSH, and 63% had experienced a standard threshold shift, as defined by the Occupational Safety and Health Administration (OSHA). All workers with an OSHA standard threshold shift had a preceding NIOSH significant threshold shift which occurred, on average, about 7 years prior. This evaluation highlights forge workers' exposures to high levels of noise, including impact noise, and how their hearing worsened with age and length of employment.
PubMed: 37818145
DOI: 10.1055/s-0043-1769498 -
Frontiers in Integrative Neuroscience 2023Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system....
INTRODUCTION
Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system. The purpose of this study was to investigate changes in vestibular end organ function in a known at-risk noise-exposed population, firefighters compared to age- and sex-matched controls using electrophysiologic measures of cervical vestibular evoked myogenic potentials (cVEMP).
METHODS
A cross-sectional observational study compared cVEMP response characteristics in 38 noise-exposed firefighters. Firefighters were grouped by years of exposure in the fire service. The cVEMP responses were compared within firefighter groups and between firefighters and age- and sex-matched controls. Dependent variables included the response characteristics of amplitude, latency and threshold.
RESULTS
cVEMP response amplitudes were significantly decreased in firefighters compared to their age- and sex-matched controls. Threshold of the cVEMP responses were significantly higher in firefighters compared to controls and firefighters had a higher incidence of absent cVEMP responses compared to controls. Response amplitudes decreased with increasing years in the fire-service at an increased rate compared to their age- and sex-matched controls. Latency of the cVEMP response was not significantly different in firefighters compared to controls. These findings are consistent with both animal and human studies suggesting noise-induced changes in the sacculocollic pathway.
DISCUSSION
In the absence of any reported vestibular symptoms or auditory indicators of noise-induced hearing loss, these early effects on the vestibular system point to a potential hidden vestibular loss.
PubMed: 37849955
DOI: 10.3389/fnint.2023.1236661