Stress and prevalence of hearing problems in the Swedish working population

<p>Abstract</p> <p>Background</p> <p>Current human and experimental studies are indicating an association between stress and hearing problems; however potential risk factors have not been established. Hearing problems are projected to become among the top ten disabilities according to the WHO in the near future. Therefore a better understanding of the relationships between stress and hearing is warranted. Here we describe the prevalence of two common hearing problems, i.e. hearing complaints and tinnitus, in relation to different work-and health-related stressors.</p> <p>Methods</p> <p>A total of 18,734 individuals were invited to participate in the study, out of which 9,756 (52%) enrolled.</p> <p>Results</p> <p>The results demonstrate a clear and mostly linear relationship between higher prevalence of hearing problems (tinnitus or hearing loss or both) and different stressors, e.g. occupational, poorer self-rated health, long-term illness, poorer sleep quality, and higher burnout scores.</p> <p>Conclusions</p> <p>The present study unambiguously demonstrates associations between hearing problems and various stressors that have not been previously described for the auditory system. These findings will open new avenues for future investigations.</p

An otoprotective role for the apoptosis inhibitor protein survivin

Hearing impairment caused by ototoxic insults, such as noise or gentamicin is a worldwide health problem. As the molecular circuitries involved are not yet resolved, current otoprotective therapies are rather empirical than rational. Here, immunohistochemistry and western blotting showed that the cytoprotective protein survivin is expressed in the human and guinea pig cochlea. In the guinea pig model, moderate noise exposure causing only a temporary hearing impairment transiently evoked survivin expression in the spiral ligament, nerve fibers and the organ of Corti. Mechanistically, survivin upregulation may involve nitric oxide (NO)-induced Akt signaling, as enhanced expression of the endothelial NO synthase and phosphorylated Akt were detectable in some surviving-positive cell types. In contrast, intratympanic gentamicin injection inducing cell damage and permanent hearing loss correlated with attenuated survivin levels in the cochlea. Subsequently, the protective activity of the human and the guinea pig survivin orthologs against the ototoxin gentamicin was demonstrated by ectopic overexpression and RNAi-mediated depletion studies in auditory cells in vitro. These data suggest that survivin represents an innate cytoprotective resistor against stress conditions in the auditory system. The pharmacogenetic modulation of survivin may thus provide the conceptual basis for the rational design of novel therapeutic otoprotective strategies

Steroid receptor expression in the fish inner ear varies with sex, social status, and reproductive state

<p>Abstract</p> <p>Background</p> <p>Gonadal and stress-related steroid hormones are known to influence auditory function across vertebrates but the cellular and molecular mechanisms responsible for steroid-mediated auditory plasticity at the level of the inner ear remain unknown. The presence of steroid receptors in the ear suggests a direct pathway for hormones to act on the peripheral auditory system, but little is known about which receptors are expressed in the ear or whether their expression levels change with internal physiological state or external social cues. We used qRT-PCR to measure mRNA expression levels of multiple steroid receptor subtypes (estrogen receptors: ERα, ERβa, ERβb; androgen receptors: ARα, ARβ; corticosteroid receptors: GR2, GR1a/b, MR) and aromatase in the main hearing organ of the inner ear (saccule) in the highly social African cichlid fish <it>Astatotilapia burtoni</it>, and tested whether these receptor levels were correlated with circulating steroid concentrations.</p> <p>Results</p> <p>We show that multiple steroid receptor subtypes are expressed within the main hearing organ of a single vertebrate species, and that expression levels differ between the sexes. We also show that steroid receptor subtype-specific changes in mRNA expression are associated with reproductive phase in females and social status in males. Sex-steroid receptor mRNA levels were negatively correlated with circulating estradiol and androgens in both males and females, suggesting possible ligand down-regulation of receptors in the inner ear. In contrast, saccular changes in corticosteroid receptor mRNA levels were not related to serum cortisol levels. Circulating steroid levels and receptor subtype mRNA levels were not as tightly correlated in males as compared to females, suggesting different regulatory mechanisms between sexes.</p> <p>Conclusions</p> <p>This is the most comprehensive study of sex-, social-, and reproductive-related steroid receptor mRNA expression in the peripheral auditory system of any single vertebrate. Our data suggest that changes in steroid receptor mRNA expression in the inner ear could be a regulatory mechanism for physiological state-dependent auditory plasticity across vertebrates.</p

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

The African Cichlid Fish Astatotilapia burtoni Uses Acoustic Communication for Reproduction: Sound Production, Hearing, and Behavioral Significance

Sexual reproduction in all animals depends on effective communication between signalers and receivers. Many fish species, especially the African cichlids, are well known for their bright coloration and the importance of visual signaling during courtship and mate choice, but little is known about what role acoustic communication plays during mating and how it contributes to sexual selection in this phenotypically diverse group of vertebrates. Here we examined acoustic communication during reproduction in the social cichlid fish, Astatotilapia burtoni. We characterized the sounds and associated behaviors produced by dominant males during courtship, tested for differences in hearing ability associated with female reproductive state and male social status, and then tested the hypothesis that female mate preference is influenced by male sound production. We show that dominant males produce intentional courtship sounds in close proximity to females, and that sounds are spectrally similar to their hearing abilities. Females were 2–5-fold more sensitive to low frequency sounds in the spectral range of male courtship sounds when they were sexually-receptive compared to during the mouthbrooding parental phase. Hearing thresholds were also negatively correlated with circulating sex-steroid levels in females but positively correlated in males, suggesting a potential role for steroids in reproductive-state auditory plasticity. Behavioral experiments showed that receptive females preferred to affiliate with males that were associated with playback of courtship sounds compared to noise controls, indicating that acoustic information is likely important for female mate choice. These data show for the first time in a Tanganyikan cichlid that acoustic communication is important during reproduction as part of a multimodal signaling repertoire, and that perception of auditory information changes depending on the animal's internal physiological state. Our results highlight the importance of examining non-visual sensory modalities as potential substrates for sexual selection contributing to the incredible phenotypic diversity of African cichlid fishes

Somatic mtDNA mutations cause progressive hearing loss in the mouse

Mitochondrial dysfunction has been implicated in the commonly occurring age-associated hearing loss (presbyacusis). We have previously generated mtDNA mutator mice with increased levels of somatic mtDNA point mutations causing phenotypes consistent with premature ageing. We have now utilized these mice to investigate whether elevated levels of somatic mtDNA mutations affect the auditory system. The mtDNA mutator mice develop a progressive impairment of hearing (ABR thresholds). Quantitative assessment of hair cell loss in the cochlea did not show any significant difference between the mutator and wild-type mice. The mtDNA mutator mice showed progressive apoptotic cell loss in the spiral ganglion and increased pathology with increasing age in the stria vascularis. The neurons in the cochlear nucleus showed an accelerated progressive degeneration with increasing age in the mutator mice compared to the wild-type mice. Both physiological and histological characterization thus reveals a striking resemblance between the auditory system pathology of mtDNA mutator mice and humans with presbyacusis. Somatic mtDNA mutations accumulate during normal ageing and further studies in humans are now warranted to investigate whether presbyacusis can be linked to mitochondrial dysfunction