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Aging Cell Sep 2023Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this...
Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.
Topics: Humans; Animals; Mice; NAD; Peroxisome Proliferator-Activated Receptors; Presbycusis; Cochlea; Dietary Supplements
PubMed: 37395319
DOI: 10.1111/acel.13909 -
Scientific Reports Nov 2023Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has...
Acoustic overexposure can eliminate synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), even if hair-cell function recovers. This synaptopathy has been extensively studied by confocal microscopy, however, understanding the nature and sequence of damage requires ultrastructural analysis. Here, we used focused ion-beam scanning electron microscopy to mill, image, segment and reconstruct ANF terminals in mice, 1 day and 1 week after synaptopathic exposure (8-16 kHz, 98 dB SPL). At both survivals, ANF terminals were normal in number, but 62% and 53%, respectively, lacked normal synaptic specializations. Most non-synapsing fibers (57% and 48% at 1 day and 1 week) remained in contact with an IHC and contained healthy-looking organelles. ANFs showed a transient increase in mitochondrial content (51%) and efferent innervation (34%) at 1 day. Fibers maintaining synaptic connections showed hypertrophy of pre-synaptic ribbons at both 1 day and 1 week. Non-synaptic fibers were lower in mitochondrial content and typically on the modiolar side of the IHC, where ANFs with high-thresholds and low spontaneous rates are normally found. Even 1 week post-exposure, many ANF terminals remained in IHC contact despite loss of synaptic specializations, thus, regeneration efforts at early post-exposure times should concentrate on synaptogenesis rather than neurite extension.
Topics: Mice; Animals; Cochlea; Noise; Hearing Loss, Noise-Induced; Hair Cells, Auditory; Hair Cells, Auditory, Inner; Synapses; Cochlear Nerve; Auditory Threshold
PubMed: 37945811
DOI: 10.1038/s41598-023-46859-6 -
Hearing Research Sep 2023Orchestration of protein production and degradation and the regulation of protein lifetimes play a central role in many basic biological processes. Nearly all mammalian... (Review)
Review
Orchestration of protein production and degradation and the regulation of protein lifetimes play a central role in many basic biological processes. Nearly all mammalian proteins are replenished by protein turnover in waves of synthesis and degradation. Protein lifetimes in vivo are typically measured in days, but a small number of extremely long-lived proteins (ELLPs) persist for months or even years. ELLPs are rare in all tissues but are enriched in tissues containing terminally differentiated post-mitotic cells and extracellular matrix. Consistently, emerging evidence suggests that the cochlea may be particularly enriched in ELLPs. Damage to ELLPs in specialized cell types, such as crystallin in the lens cells of the eye, causes organ failure such as cataracts. Similarly, damage to cochlear ELLPs is likely to occur with many insults, including acoustic overstimulation, drugs, anoxia, and antibiotics, and may play an underappreciated role in hearing loss. Furthermore, hampered protein degradation may contribute to acquired hearing loss. In this review, I highlight our knowledge of the lifetimes of cochlear proteins with an emphasis on ELLPs and the potential contribution that impaired cochlear protein degradation has on acquired hearing loss and the emerging relevance of ELLPs.
Topics: Animals; Hearing Loss, Noise-Induced; Cochlea; Deafness; Mammals
PubMed: 37295280
DOI: 10.1016/j.heares.2023.108821 -
Age and Ageing Aug 2023Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life....
Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life. Hearing is affected by multiple factors, including heredity, noise exposure, age, sex, ear disorders and lifestyle factors. Globally, hearing loss affects over 80% of adults aged 80 years and older, is often experienced in combination with other long-term health conditions and is a mid-life risk factor for dementia. To form a themed collection, we searched Age and Ageing for articles on hearing conditions published from 2000 onwards. This resulted in 22 articles included within the collection. They examined a range of important topics related to hearing healthcare and research, including noise-induced hearing loss, health service quality and safety, psychological and psychosocial consequences of hearing loss and co-morbidities of hearing loss. All articles reported on hearing loss; there were no published articles with a primary focus on other hearing conditions such as tinnitus or hyperacusis, on the health of older people from the Deaf community or on users of Cochlear implants, suggesting key gaps in knowledge and targets for future research. This New Horizons article highlights novel directions in research and practice and takes a forward look at how research into hearing conditions may develop in years to come. It highlights opportunities for the growth of patient-centred research and hearing healthcare supported by the better integration of health and care services as well as cross-speciality working to include common co-morbid health conditions.
Topics: Humans; Aged; Tinnitus; Hyperacusis; Quality of Life; Hearing; Aging
PubMed: 37604677
DOI: 10.1093/ageing/afad150 -
Frontiers in Cellular Neuroscience 2024Efferent feedback to the mammalian cochlea includes cholinergic medial olivocochlear neurons (MOCs) that release ACh to hyperpolarize and shunt the voltage change that... (Review)
Review
Efferent feedback to the mammalian cochlea includes cholinergic medial olivocochlear neurons (MOCs) that release ACh to hyperpolarize and shunt the voltage change that drives electromotility of outer hair cells (OHCs). Via brainstem connectivity, MOCs are activated by sound in a frequency- and intensity-dependent manner, thereby reducing the amplification of cochlear vibration provided by OHC electromotility. Among other roles, this efferent feedback protects the cochlea from acoustic trauma. Lesion studies, as well as a variety of genetic mouse models, support the hypothesis of efferent protection from acoustic trauma. Genetic knockout and gain-of-function knockin of the unique α9α10-containing nicotinic acetylcholine receptor (nAChR) in hair cells show that acoustic protection correlates with the efficacy of cholinergic inhibition of OHCs. This protective effect was replicated by viral transduction of the gain-of-function α9L9'T nAChR into α9-knockout mice. Continued progress with "efferent gene therapy" will require a reliable method for visualizing nAChR expression in cochlear hair cells. To that end, mice expressing HA-tagged α9 or α10 nAChRs were generated using CRISPR technology. This progress will facilitate continued study of the hair cell nAChR as a therapeutic target to prevent hearing loss and potentially to ameliorate associated pathologies such as hyperacusis.
PubMed: 38560293
DOI: 10.3389/fncel.2024.1372948 -
CoDAS 2023To identify the pathophysiological definitions adopted by studies investigating "cochlear synaptopathy" (CS) and "hidden hearing loss" (HHL). (Review)
Review
PURPOSE
To identify the pathophysiological definitions adopted by studies investigating "cochlear synaptopathy" (CS) and "hidden hearing loss" (HHL).
RESEARCH STRATEGIES
The combination of keywords "Auditory Synaptopathy" or "Neuronal Synaptopathy" or "Hidden Hearing Loss" with "etiology" or "causality" or "diagnosis" was used in the databases EMBASE, Pubmed (MEDLINE), CINAHL (EBSCO), and Web of Science.
SELECTION CRITERIA
Studies that investigated CS or HHL in humans using behavioral and/or electrophysiological procedures were included.
DATA ANALYSIS
Data analysis and extraction were performed with regard to terminology, definitions, and population.
RESULTS
49 articles were included. Of these, 61.2% used the CS terminology, 34.7% used both terms, and 4.1% used HHL. The most-studied conditions were exposure to noise and tinnitus.
CONCLUSION
CS terminology was used in most studies, referring to the pathophysiological process of deafferentiation between the cochlear nerve fibers and inner hair cells.
Topics: Humans; Hearing Loss, Noise-Induced; Auditory Threshold; Evoked Potentials, Auditory, Brain Stem; Cochlea; Noise; Deafness
PubMed: 37991055
DOI: 10.1590/2317-1782/20232023032pt -
HNO Aug 2023This cross-sectional study aimed to assess the frequency and type of firework-associated acoustic trauma occurring in Germany on New Year's Eve 2021, despite the ban on...
BACKGROUND
This cross-sectional study aimed to assess the frequency and type of firework-associated acoustic trauma occurring in Germany on New Year's Eve 2021, despite the ban on firework sales due to the COVID-19 pandemic.
MATERIALS AND METHODS
The survey period lasted 7 days, from 28 December 2021 to 03 January 2022. A questionnaire inquired date, type and treatment of trauma, sex, and age of the patient, and whether the trauma occurred when lighting or watching fireworks. Hearing impairment was classified according to the World Health Organization (WHO grades 0 to 4), and concomitant tinnitus, vertigo, or other injuries were recorded. The questionnaire was sent to the otorhinolaryngology departments of 171 hospitals in Germany.
RESULTS
Of 37 otorhinolaryngology departments, 16 reported no and 21 reported 50 patients with firework-associated acoustic trauma. Mean age was 29 ± 16 years and 41 of 50 patients were males. Of these 50 patients, 22 presented without and 28 with hearing loss, 32 reported tinnitus and 3 vertigo; 20 patients were injured when lighting fireworks and 30 when watching. Hearing impairment was classified as 14 × WHO grade 0, 5 × WHO grade 1, 4 × WHO grade 2, 2 × WHO grade 3, and 3 × WHO grade 4. Inpatient treatment was received by 8 patients and 11 suffered from concomitant burn injuries.
CONCLUSION
Despite the sales ban, some firework-associated acoustic traumas occurred at New Year 2021/2022 in Germany. Some instances led to hospitalization, but an even higher number of unreported cases can be assumed. This study can serve as a baseline for further annual surveys to raise the awareness of the danger of seemingly harmless fireworks for the individual.
Topics: Male; Humans; Adolescent; Young Adult; Adult; Middle Aged; Female; Blast Injuries; Hearing Loss, Noise-Induced; Lightning; Cross-Sectional Studies; Pandemics; Tinnitus; COVID-19
PubMed: 36847786
DOI: 10.1007/s00106-022-01260-z