Hearing Research最新文献

Age-related hearing loss (ARHL) is a widespread problem in the elderly, significantly impairing their quality of life. Despite its high prevalence, no fundamental treatment for ARHL has been established. Nicotinamide adenine dinucleotide (NAD⁺) is required for various biological processes and tissue levels of the coenzyme NAD⁺ are known to decrease with age. A previous report suggested that declining NAD⁺ levels induce age-related diseases and NAD⁺ supplementation might be effective for treating or preventing age-related diseases. To clarify the effect of NAD⁺ supplementation on ARHL, C57BL/6J mice used as an animal model of ARHL were treated with nicotinamide mononucleotide (NMN), a precursor of NAD⁺. Oral administration of NMN at 500 mg/kg/day effectively suppressed the development of ARHL in C57BL/6J mice. To elucidate the mechanism by which NMN administration suppressed the development of ARHL, NAD⁺-related metabolites were assessed, and a comprehensive transcriptomic analysis of the inner ear tissue was performed. NMN administration resulted in increased NAD⁺ levels in inner ear tissues and induced changes in the transcriptome, specifically in genes related to metal ion metabolism. These findings suggest that NMN administration enhanced NAD⁺ levels in inner ear tissues, modulating metal ion metabolism to potentially protect against oxidative stress. This study provides a novel therapeutic approach to mitigating ARHL through NAD⁺ supplementation.

Objectives: Understanding brain processing of auditory and visual speech is essential for advancing speech perception research and improving clinical interventions for individuals with hearing impairment. Functional near-infrared spectroscopy (fNIRS) is deemed to be highly suitable for measuring brain activity during language tasks. However, accurate data interpretation also requires validated stimuli and behavioral measures.

Design: Twenty-six adults with normal hearing listened to sentences from the Oldenburg Sentence Test (OLSA), and brain activation in the temporal, occipital, and prefrontal areas was measured by fNIRS. The sentences were presented in one of the four different modalities: speech-in-quiet, speech-in-noise, audiovisual speech or visual speech (i.e., lipreading). To support the interpretation of our fNIRS data, and to obtain a more comprehensive understanding of the study population, we performed hearing tests (pure tone and speech audiometry) and collected behavioral data using validated questionnaires, in-task comprehension questions, and listening effort ratings.

Results: In the auditory conditions (i.e., speech-in-quiet and speech-in-noise), we observed cortical activity in the temporal regions bilaterally. During the visual speech condition, we measured significant activation in the occipital area. Following the audiovisual condition, cortical activation was observed in both regions. Furthermore, we established a baseline for how individuals with normal hearing process visual cues during lipreading, and we found higher activity in the prefrontal cortex in noise conditions compared to quiet conditions, linked to higher listening effort.

Conclusions: We demonstrated the applicability of a clinically inspired audiovisual speech-comprehension task in participants with normal hearing. The measured brain activation patterns were supported and complemented by objective and behavioral parameters.

Background: Vestibular schwannomas (VS) are complex and heterogeneous human tumors arising from the Schwann cell compartment of the vestibulocochlear nerve. VS cause significant neurological deficit such as hearing loss and vestibular impairment, and in some cases death due to brainstem compression. There is an urgent need to find pharmacotherapies for VS since surgical removal and stereotactic radiosurgery are the only effective treatments. Cancer therapy based in the combination of drug-induced senescence and senolytics may provide an innovative pharmacological alternative for VS management.

Methods: Senescence-associated β-galactosidase (SA-β-GAL) activity detection assay, real-time polymerase chain reaction (RT-PCR), western blotting and immunofluorescence, together with viability assays were used to analyze the response to different chemotherapy drugs of the human VS HEI-193 cell line. Human VS tumor paraffin sections were also studied for SA-β-GAL-stained cells.

Results: We found that chemotherapy compounds induced genotoxic stress and cellular senescence in HEI-193 VS cells, as characterized by increased SA-β-GAL activity, growth arrest, increased levels of the cyclin-dependent kinase inhibitor p21 and the accumulation of DNA damage. These cellular senescence markers were also accompanied by an increase of senescence-associated secretory phenotype (SASP): IL6, IL8, IL1B and MMP1. Induction of senescence by chemotherapy rendered HEI-193 VS cells as druggable targets for senolytic compounds, as navitoclax. Thus, treatment with navitoclax selectively eliminated bleomycin-induced senescent HEI-193 VS cells by activating the extrinsic and intrinsic apoptosis pathways. Our data also show the presence of senescent cells, SA-β-GAL-positive stain, in human VS tumors, which are not present in healthy great auricular nerve sections.

Conclusions: These findings suggest that a one-two punch strategy of pro-senescence therapy induced by chemotherapy treatment followed by senolytic therapy represents a new paradigm for the pharmacological treatment of VS.

Background: Tinnitus, defined as the conscious awareness of a noise without any identifiable corresponding external acoustic source, can be modulated by various factors. Among these factors, tinnitus patients commonly report drastic increases of tinnitus loudness following nap sleep. Previous studies have suggested that this clinical pattern could be attributed to a somatosensory modulation of tinnitus. To our knowledge, no polysomnographic study has been carried out to assess this hypothesis.

Methods: For this observational prospective study, 37 participants reporting frequent increases of tinnitus following naps were recruited. They participated to six full-polysomnography nap attempts over two days. Audiological and kinesiologic tests were conducted before and after each nap attempt.

Results: 197 naps were collected. Each nap at each time of day elicited an overall significant increase in tinnitus minimum masking level (MML). Each inter nap period elicited an overall significant decrease. Tinnitus modulations were found significantly correlated with nap sleep duration (Visual numeric scale on tinnitus loudness, VNS-L, p < 0.05), with snoring duration (MML, p < 0.001), with snoring average sound level (VNS on tinnitus intrusiveness, VNS-I, p < 0.05) and with sleep apnea count (VNS-I, p < 0.001).

Conclusions: This study confirms objectively that tinnitus may increase following naps. No association was found between these modulations and somatosensory modulations involving the temporomandibular joint and cervical areas. However, it may be possible that nap-induced tinnitus modulations are a hidden form of somatosensory modulation as snoring and sleep apnea events are often related to tensor veli palatini muscle dysfunction.

Beginning in 2006, optical coherence tomography (OCT) has been adapted for use as a vibrometer for hearing research. The application of OCT in this field, particularly for studying cochlear mechanics, represents a revolutionary advance over previous technologies. OCT provides detailed evidence of the motions of components within the organ of Corti, extending beyond the first-encountered surface of observation. By imaging through the bony capsule as well as through the round window membrane, OCT has measured vibration at multiple locations along the cochlear spiral, in vivo, under nearly natural conditions. In this document, we present examples of recent research findings to illustrate the applications of OCT in studying cochlear mechanics in both normal and impaired ears.

The auditory system is constantly tasked with detecting acoustic cues in complex auditory environments. Difficulty hearing speech in noise, largely a result of energetic masking, is a major communication complaint of the elderly, which impacts a third of the global population over 65. The neural mechanisms responsible for processing sound in background noise and subsequently achieving release from energetic masking remain obscure. Furthermore, the senescence of signal-in-noise detection is poorly understood, a phenomenon which could have a myriad of clinical implications. We tested over 300 CBA/CaJ mice aged 1-27 months on tone-in-noise detection ability utilizing prepulse inhibition of the acoustic startle response with a machine learning startle classifier. We found that mice developed profound tone-in-noise detection deficits throughout their lifespan as evidenced by Rd', a detection metric derived from signal detection theory. The most severe decline in Rd' corresponded to a 2.54-fold decrease in tone-in-noise detection across the lifespan. Our findings suggest that CBA/CaJ mice are an appropriate model to study the role of age-related hearing loss in the context of signal-in-noise masking.

Auditory-nerve fibers (ANFs) from a given cochlear region can vary in threshold sensitivity by up to 60 dB, corresponding to a 1000-fold difference in stimulus level, although each fiber innervates a single inner hair cell (IHC) via a single synapse. ANFs with high-thresholds also have low spontaneous rates (SRs) and synapse on the side of the IHC closer to the modiolus, whereas the low-threshold, high-SR fibers synapse on the side closer to the pillar cells. Prior biophysical work has identified modiolar-pillar differences in both pre- and post-synaptic properties, but a comprehensive explanation for the wide range of sensitivities remains elusive. Here, in guinea pigs, we used immunostaining for several neuronal markers, including Caspr, a key protein in nodes of Ranvier, to reveal a novel modiolar-pillar gradient in the location of the first ANF heminodes, presumed to be the site of the spike generator, just outside the sensory epithelium. Along the cochlea, from apex to base, the unmyelinated terminal dendrites of modiolar ANFs were 2-4 times longer than those of pillar ANFs. This modiolar-pillar gradient in dendritic length, coupled with the 2-4 fold smaller caliber of modiolar dendrites seen in prior single-fiber labeling studies, suggests there could be a large difference in the number of length constants between the synapse and the spike initiation zone for low- vs high-SR fibers. The resultant differences in attenuation of post-synaptic potentials propagating along these unmyelinated dendrites could be a key contributor to the observed range of threshold sensitivities among ANFs.

Hearing loss, particularly age-related hearing loss, significantly impacts health and quality of life worldwide. While much of the research has focused on older adults, the early stages of hearing decline remain relatively unexplored. Longitudinal studies examining hearing changes across the adult lifespan, especially at extended high frequencies (EHFs), are scarce. This prospective longitudinal study aimed to explore the rate of hearing threshold shift in young adults with clinically normal audiograms and to assess whether EHF hearing loss could predict future hearing decline in the standard audiometric range. Hearing thresholds were measured at standard audiometric frequencies (0.25 to 8 kHz) and EHFs (10, 12.5, 14, and 16 kHz) in 71 participants (24 females) aged 19 to 38 years (mean age = 27.8 years). Two testing sessions were conducted nearly 24 months apart. Results revealed that the annual rate of threshold shift was significantly higher for EHFs compared to standard audiometric frequencies. A higher EHF threshold, measured in the initial test session, was associated with a greater rate of threshold shift at standard audiometric frequencies, suggesting that EHF hearing loss may serve as an early marker for subsequent hearing decline. Even with a normal audiogram, individuals with EHF hearing loss are at an increased risk of accelerated hearing deterioration. These findings show preclinical, age-related changes in young adults with normal audiograms and underscore the importance of early detection and monitoring of EHF hearing loss to mitigate the impact of future hearing loss on their overall health and well-being.