Premature Hearing Loss Research Articles

Pharmacological Modulation of Energy and Metabolic Pathways Protects Hearing in the Fus1/Tusc2 Knockout Model of Mitochondrial Dysfunction and Oxidative Stress.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1/Tusc2 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, and altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether the pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1/Tusc2-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed the dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and the cochlear hypothalamic-pituitary-adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins and calcium-linked transporters and voltage-gated channels. These findings suggest that the pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss.

Hypakuze u pacientů s Fabryho chorobou

Introduction: Fabry disease (FD) is a rare hereditary lysosomal storage disease aff ecting diff erent organs, including the cochlea-vestibular system. It can lead to premature hearing loss and tinnitus. Early and correct dia gnosis of FD is important with a view of available therapy. Purpose: The aim of this study is to evaluate the degree of hearing loss in patients with FD. Additionally, to compare diff erences between male and female patients as well as the diff erences of types of FD in patients with diff erent phenotypes. Methods: This is a retrospective study of patients that had been examined in our out-patient offi ce in the years 2016–2020. We used 7-tone pure-tone audiometry (0,125–8 kHz). We compared audiograms of patients right and left ear, calculated average Fowler percentage of hearing loss on left ear, right ear and combined. We compared combined Fowler percentage of hearing loss in diff erent types of FD based on the disease phenotype. Moreover, we compared the progress of hearing loss in time in patients that were examined in our offi ce more than once. Results: We examined 121 patients (55 male, 66 female) with dia gnosed FD. Female patients exhibited 48.5% hearing loss in the right ear and 50% in the left ear. Mixed hearing loss occurred in 1.5% of females in the group. We observed sensorineural hearing loss in 63.6% in the right ear and 65.5% in the left ear within male patients. Mixed hearing loss appeared in 1.8% of male patients. Combined mean Fowler percentage of hearing loss in females was 8.8 % and in males 14.8 %. Female patients with the classic type of FD had signifi cantly worse hearing than females with any other type of FD. This was not observed in the male group. Conclusion: Patients with FD in our group of patients had mostly sensorineural hearing loss. Hearing loss of male patients with FD was signifi cantly worse than females. Keywords: hearing loss – Fabry disease – phenotype – alpha-galactosidase – audiometry

Cdk5 regulatory subunit-associated protein 1 knockout mice show hearing loss phenotypically similar to age-related hearing loss

Mitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables efficient intramitochondrial translation by catalyzing the deposition of 2-methylthio modifications on mitochondrial tRNAs. Here we investigated the effect of defective mitochondrial protein translation on hearing and AHL in a Cdk5rap1 deficiency C57BL/6 mouse model. Compared to control C57BL/6 mice, Cdk5rap1-knockout female mice displayed hearing loss phenotypically similar to AHL from an early age. The premature hearing loss in Cdk5rap1-knockout mice was associated with the degeneration of the spiral ligament and reduction of endocochlear potentials following the loss of auditory sensory cells. Furthermore, cultured primary mouse embryonic fibroblasts displayed early onset of cellular senescence associated with high oxidative stress and cell death. These results indicate that the CDK5RAP1 deficiency-induced defective mitochondrial translation might cause early hearing loss through the induction of cellular senescence and cochlear dysfunction in the inner ear. Our results suggest that the accumulation of dysfunctional mitochondria might promote AHL progression. Furthermore, our findings suggest that mitochondrial dysfunction and dysregulated mitochondrial tRNA modifications mechanistically cause AHL. Understanding the mechanisms underlying AHL will guide future clinical investigations and interventions in the attempt to mitigate the consequences of AHL.

A CASE OF MID-FREQUENCY SENSORINEURAL HEARING LOSS

Introduction: Mid-frequency sensorineural hearing loss (MFSNHL) is an unusual audiometric finding with a debatable etiology with unclear long-term results. In general, the middle frequencies are affected first, and the process progresses slowly to include all frequencies. There are also some cases where provocative factors have been reported. Purpose: The aim of the work is to present a clinical case in our practice of the rare occurrence of mid-frequency acoustic hearing loss and its diagnostic approach. Material and methods: The patient has undergone a number of manual and instrumental tests to confirm or reject a specific cause of the hearing loss condition. Results: A 52-year-old man was hospitalised with complaints of hearing loss for about a year, judging by the growing difficulty in making a phone call. Conclusions: Generally, a U-shaped audiogram is thought to indicate hearing loss of genetic origin. However, this type of deafness is not unique to one particular type of genetic mutation. There are also numerous descriptions of non-genetic mid-frequency hearing loss in the literature. In the particular clinical case presented by us, it was concluded that this was a hearing loss, possibly of hereditary nature, after excluding another provocative cause, as well as due to anamnestic data on premature hearing loss in one of the parents.

Perceptions, Beliefs, and Attitudes Toward Various Hearing Conservation Approaches Reported by Indiana College Agriculture Students

HighlightsNoise-measuring applications (apps) and in-person classroom presentation were identified as the most preferred approaches by the college agriculture students.Multiple features of noise apps and in-person intervention were identified as beneficial.A subset of participants reported that a combination of approaches could influence hearing protection use.Abstract. Noise-induced hearing loss is a major public health challenge for agricultural communities. However, there is limited hearing conservation research addressing the issue, especially for youth and young adults. The purpose of this study was to investigate the perceptions and practices of Indiana undergraduate students who lived or worked on a farm. The students were asked to rank the most common and current hearing conservation educational approaches, including in-person classroom presentation, mailers, and technology-based approaches, i.e., computer-based training, interactive websites, static websites, and smartphone noise-measuring applications (apps). A total of 91 undergraduate students enrolled in agriculture classes at four Indiana higher educational institutions participated in the study. They completed a sociodemographic and farm activity survey, followed by a 30-minute in-person presentation on hearing health conservation. After the presentation, each participant completed a questionnaire that included items about their perceptions of the feasibility, sustainability, rankings, and preferences of the various educational approaches discussed in the presentation. Participants ranked the noise-measuring app and in-person classroom presentation as their most preferred educational approaches for hearing conservation (39% and 28%, respectively). They identified multiple features of these two intervention approaches as beneficial. Sixty-four percent of participants indicated that a combination of approaches could influence hearing protection use and should include in-person classroom presentation and one of the technology-based approaches (noise-measuring apps, 37.3%). These findings are expected to assist health interventionists and program designers in developing future hearing protection education programs for farm youth, who may otherwise lack access to resources for preventing premature hearing loss due to loud noise exposure. Keywords: Agricultural workers, Hearing conservation, Hearing protection, Undergraduate college students, Youth education.

Spatial Variation in Sound Frequency Components Across an Urban Area Derived from Mobile Surveys

Continuous exposure to noise can lead to premature hearing loss, reduced cognitive performance, insomnia, stress, hypertension, cardiovascular diseases and stroke. Road noise affects the health of >125 million people in the European Union and Member States are required to map major noise hotspots. These strategic noise maps are usually derived from traffic counts and propagation models because large- scale measurement of the acoustic environment using conventional methods is infeasible. In this study, the authors surveyed the entire city of Southampton, UK using a mobile survey technique, capturing spatial variations in street-level sound characteristics across multiple frequencies from all sound sources. Over 52,000 calibrated and georeferenced sound clips covering 11 Hz to 22.7 kHz are analysed here to investigate variations in sound frequency composition across urban space and then applied to two issues: the definition of naturalness in the acoustic environment; and perceptions of social inequity in sound exposure. Clusters of acoustic characteristics were identified and mapped using spectral clustering and principal components analysis based on octave bands, ecoacoustic indices and dBA. We found independent patterns in low, mid and high frequencies, and the ecoacoustic indices that related to land use. Ecoacoustic indices partially mapped onto greenspace, identifying naturalness, but not uniquely, probably because urban anthropogenic sounds occur at higher frequencies than in the natural areas where such indices were developed. There was some evidence of inequity in sound exposure according to social deprivation and ethnicity, and results differed according to frequency bands. The consequences of these findings and the benefits of city-wide sound surveys for urban planning are discussed.

Novel Role of the Mitochondrial Protein Fus1 in Protection from Premature Hearing Loss via Regulation of Oxidative Stress and Nutrient and Energy Sensing Pathways in the Inner Ear.

Acquired hearing loss is a worldwide epidemic that affects all ages. It is multifactorial in etiology with poorly characterized molecular mechanisms. Mitochondria are critical components in hearing. Here, we aimed to identify the mechanisms of mitochondria-dependent hearing loss using Fus1 KO mice, our novel model of mitochondrial dysfunction/oxidative stress. Using auditory brainstem responses (ABRs), we characterized the Fus1 KO mouse as a novel, clinically relevant model of age-related hearing loss (ARHL) of metabolic etiology. We demonstrated early decline of the endocochlear potential (EP) that may occur due to severe mitochondrial and vascular pathologies in the Fus1 KO cochlear stria vascularis. We showed that pathological alterations in antioxidant (AO) and nutrient and energy sensing pathways (mTOR and PTEN/AKT) occur in cochleae of young Fus1 KO mice before major hearing loss. Importantly, short-term AO treatment corrected pathological molecular changes, while longer AO treatment restored EP, improved ABR parameters, restored mitochondrial structure, and delayed the development of hearing loss in the aging mouse. Currently, no molecular mechanisms linked to metabolic ARHL have been identified. We established pathological and molecular mechanisms that link the disease to mitochondrial dysfunction and oxidative stress. Since chronic mitochondrial dysfunction is common in many patients, it could lead to developing hearing loss that can be alleviated/rescued by AO treatment. Our study creates a framework for clinical trials and introduces the Fus1 KO model as a powerful platform for developing novel therapeutic strategies to prevent/delay hearing loss associated with mitochondrial dysfunction. Antioxid. Redox Signal. 27, 489-509.

Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism

Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism

Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism.

Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress.

Noise-induced hearing loss among workers in textile factory

Abstract Noise-induced hearing loss (NIHL) is one of the most common chronic health problems, which produces gradual progressive impairment and disturbs the patient’s quality of life. Industries in general and especially textile ones produce noise levels that, if intensified, can cause damage to worker’s hearing. Hence, premature hearing loss is a well-known outcome of noise exposure at work in industrial workers. The aim of the study was to assess hearing threshold levels among exposed patients and to compare them with the nonexposed control group and to evaluate other variables such as outer hair cell and medial olivocochlear bundle function represented with transient evoked otoacoustic emissions (TEOAEs) testing with and without suppression and to find the relationship with duration of exposure if any. The study included 145 patients and same number of controls who were exposed to hazardous levels of noise for variable durations. All participants were subjected to audiological examination including basic audiological evaluation, otoacoustic emissions, and otoacoustic emissions with contralateral suppression (CAS). Of the 145 patients (290 ears), 214 ears showed sensorineural hearing loss (73.8%). Sensorineural hearing loss was mild in 63 (43.44%) ears, moderate in 82 (56.55%) ears, and severe in 69 (47.58%) ears. TEOAEs were found in those with mild hearing loss with significantly lower amplitudes. Intact suppression (CAS) was significantly lower for the study group than for the control group. However, there was no significant difference in level of suppression for different duration of exposure. A high incidence for NIHL is present among workers in textile factories, which indicate the mandatory use of different protective measures. CAS can be used as a predictor for the susceptibility to NIHL.

Description of a new family with cryopyrin-associated periodic syndrome: risk of visual loss in patients bearing the R260W mutation

The aim of this study was to describe a family with cryopyrin-associated periodic syndrome (CAPS) in which the disease was unveiled after the ophthalmologic evaluation. Family and personal histories from each of the patients were recorded. Each underwent a full ophthalmological examination along with the physical examination. The mutational analysis of the NLRP3 gene was performed by means of direct sequencing. The proband was admitted during an episode of unilateral anterior uveitis. She had a history of recurrent red eye and had been suffering episodes of skin rash and arthralgia induced by cold since childhood. At examination, she showed a reticulated corneal mid-stroma. Her mother and her younger sister also suffered from relapsing episodes of skin rash and fever triggered by cold as well as flares of red eye. They had developed premature hearing loss. In both cases, opacities in the corneal mid-stroma were evidenced with a slit lamp. The genetic analysis detected the heterozygous germline p.R260W mutation in the NLRP3 gene in the three women, confirming the diagnosis of CAPS. Treatment with anakinra resulted in complete remission of flares. In this family, a structural NLRP3 mutation was associated with classic MuckleWells features of different degrees of severity. Interstitial keratitis with corneal opacification, usually ascribed to neonatal-onset multisystem inflammatory disease, was found. We underscore that ocular involvement in MuckleWells syndrome should be carefully assessed, since it can lead to visual impairment.

Oxidative Stress, Inflammation, and Autophagic Stress as the Key Mechanisms of Premature Age-Related Hearing Loss in SAMP8 Mouse Cochlea

In our aging society, age-related hearing loss (ARHL) or presbycusis is increasingly important. Here, we study the mechanism of ARHL using the senescence-accelerated mouse prone 8 (SAMP8) which is a useful model to probe the effects of aging on biological processes. We found that the SAMP8 strain displays premature hearing loss and cochlear degeneration recapitulating the processes observed in human presbycusis (i.e., strial, sensory, and neural degeneration). The molecular mechanisms associated with premature ARHL in SAMP8 mice involve oxidative stress, altered levels of antioxidant enzymes, and decreased activity of Complexes I, II, and IV, which in turn lead to chronic inflammation and triggering of apoptotic cell death pathways. In addition, spiral ganglion neurons (SGNs) also undergo autophagic stress and accumulated lipofuscin. Our results provide evidence that targeting oxidative stress, chronic inflammation, or apoptotic pathways may have therapeutic potential. Modulation of autophagy may be another strategy. The fact that autophagic stress and protein aggregation occurred specifically in SGNs also offers promising perspectives for the prevention of neural presbycusis.

Involuntary and Persistent Environmental Noise Influences Health and Hearing in Beirut, Lebanon

Objective. This study was conducted to assess the effects of involuntary and persistent noise exposure on health and hearing among Lebanese adults in Beirut, Lebanon, where people are exposed to noise from construction sites, power generators, honking cars, and motorcycles. Methods. Using a descriptive and exploratory design with mixed methods, participants were surveyed, interviewed, and tested for hearing while street noise levels were measured near their residents and work places. Results. Self-reports of 83 Lebanese adult, who lived and worked in Beirut, helped identify common patterns in experiences such as irritability, anger, headaches, and sleep disturbances due to noise annoyance. Of those tested, 30% suffered from high-frequency hearing impairment. Our results showed that environmental sound dB had increased by 12% and sound intensity by 400% above the maximum standard level when compared to the WHO report of 1999. Conclusion. Environmental noise contributes to premature hearing loss and potentiates systemic diseases among Lebanese.

Effects of Submaximal Exercise and Noise Exposure on Hearing Loss

A recent Scandinavian study reported that persons cycling at moderate intensity for 10 min suffered hearing loss when the exercise was accompanied by noise. The noise consisted of a 1/3 octave band-filtered noise with a 2000 Hz center frequency at 104 dB SPL. In the present study, adults cycled at 50 rev.min-1 against a force that elicited an oxygen cost equal to 70% of VO2max--an intensity frequently recommended in exercise prescriptions--with and without noise administered via headphones. Repeated measures ANOVA with three factors revealed that although a temporary hearing loss occurred following exercise-and-noise, a similar and slightly greater hearing loss occurred following noise-only. Hearing sensitivity was not significantly altered by exercise-only (p greater than .05). In general, hearing loss values were greatest between 3000 and 4000 Hz. In conclusion, temporary hearing loss was driven by noise exposure, not exercise. However, persons who choose to exercise with personal headphones or in a noisy environment should be aware of potential premature hearing loss.

Trembling chin — a report of this inheritable dominant character in a four‐generation Canadian family

Trembling chin is an unusual, benign, dominant trait. We describe the condition in a four-generation Canadian family. Investigations, which included E.E.G., electromyograph and facial nerve conductance studies on affected and unaffected individuals, were normal. Premature hearing loss, present in all affected members of this family over age 50, strongly suggests an association of trembling chin with otosclerosis. The merits of early diagnosis and preventive treatment for otosclerosis in persons affected by trembling chin are discussed.