scholarly journals Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway

2020 ◽  
Author(s):  
Barbara Peixoto Pinheiro ◽  
Barbara Vona ◽  
Hubert Löwenheim ◽  
Lukas Rüttiger ◽  
Marlies Knipper ◽  
...  
Keyword(s):  
Hair Cells ◽  
Noise Exposure ◽  
Auditory Pathway ◽  
Surface Expression ◽  
Potassium Ion ◽  
Outer Hair Cells ◽  
Potassium Ion Channels ◽  
Potassium Ion Channel ◽  
Age Related ◽  
Age Related Hearing Loss

AbstractAge-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance of the potassium ion channel KV7.4 (KCNQ4) in outer hair cells, inspiring future therapies to maintain or prevent the decline of potassium ion channel surface expression to reduce ARHL. In concert with KV7.4 in outer hair cells, KV7.1 (KCNQ1) in the stria vascularis, calcium-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) in hair cells and efferent fiber synapses, and KV3.1 (KCNC1) in the spiral ganglia and ascending auditory circuits share an upregulated expression or subcellular targeting during final differentiation at hearing onset. They also share a distinctive fragility for noise exposure and age-dependent shortfalls in energy supply required for sustained surface expression. Here, we review and discuss the possible contribution of select potassium ion channels in the cochlea and auditory pathway to ARHL. We postulate genes, proteins, or modulators that contribute to sustained ion currents or proper surface expressions of potassium channels under challenging conditions as key for future therapies of ARHL.

scholarly journals Preventing presbycusis in mice with enhanced medial olivocochlear feedback

2020 ◽  
Vol 117 (21) ◽  
pp. 11811-11819 ◽  
Author(s):  
Luis E. Boero ◽  
Valeria C. Castagna ◽  
Gonzalo Terreros ◽  
Marcelo J. Moglie ◽  
Sebastián Silva ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Auditory Brainstem Responses ◽  
Cochlear Function ◽  
Gain Of Function ◽  
Distortion Product ◽  
Age Related ◽  
Medial Olivocochlear ◽  
Age Related Hearing Loss

“Growing old” is the most common cause of hearing loss. Age-related hearing loss (ARHL) (presbycusis) first affects the ability to understand speech in background noise, even when auditory thresholds in quiet are normal. It has been suggested that cochlear denervation (“synaptopathy”) is an early contributor to age-related auditory decline. In the present work, we characterized age-related cochlear synaptic degeneration and hair cell loss in mice with enhanced α9α10 cholinergic nicotinic receptors gating kinetics (“gain of function” nAChRs). These mediate inhibitory olivocochlear feedback through the activation of associated calcium-gated potassium channels. Cochlear function was assessed via distortion product otoacoustic emissions and auditory brainstem responses. Cochlear structure was characterized in immunolabeled organ of Corti whole mounts using confocal microscopy to quantify hair cells, auditory neurons, presynaptic ribbons, and postsynaptic glutamate receptors. Aged wild-type mice had elevated acoustic thresholds and synaptic loss. Afferent synapses were lost from inner hair cells throughout the aged cochlea, together with some loss of outer hair cells. In contrast, cochlear structure and function were preserved in aged mice with gain-of-function nAChRs that provide enhanced olivocochlear inhibition, suggesting that efferent feedback is important for long-term maintenance of inner ear function. Our work provides evidence that olivocochlear-mediated resistance to presbycusis-ARHL occurs via the α9α10 nAChR complexes on outer hair cells. Thus, enhancement of the medial olivocochlear system could be a viable strategy to prevent age-related hearing loss.

scholarly journals Repair of Noise-Induced Damage to Stereocilia F-actin Cores is Facilitated by XIRP2

2021 ◽  
Author(s):  
Elizabeth L Wagner ◽  
Jun-Sub Im ◽  
Maura I Nakahata ◽  
Terence E Imbery ◽  
Sihan Li ◽  
...  
Keyword(s):  
Hair Cells ◽  
Noise Exposure ◽  
Prolonged Exposure ◽  
Hearing Threshold ◽  
Repair Process ◽  
Auditory Hair Cells ◽  
Age Related ◽  
C Terminus ◽  
Actin Nucleator ◽  
Age Related Hearing Loss

Prolonged exposure to loud noise has been shown to affect inner ear sensory hair cells in a variety of deleterious manners, including damaging the stereocilia core. The damaged sites can be visualized as gaps in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments. Herein we show that gaps in mouse auditory hair cells are largely repaired within one week of traumatic noise exposure through the incorporation of newly synthesized actin. Additionally, we report that XIRP2 is required for the repair process and facilitates the enrichment of monomeric γ-actin at gaps through its LIM domain-containing C-terminus. Our study describes a novel process by which hair cells can recover from sub-lethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss.

scholarly journals Bcl11b Heterozygosity Leads to Age-Related Hearing Loss and Degeneration of Outer Hair Cells of the Mouse Cochlea

2011 ◽  
Vol 60 (4) ◽  
pp. 355-361 ◽  
Author(s):  
Hitoshi OKUMURA ◽  
Yuki MIYASAKA ◽  
Yuka MORITA ◽  
Tomoyuki NOMURA ◽  
Yukio MISHIMA ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Age Related ◽  
Age Related Hearing Loss

Differential Expression of Bcl-2 in the Cochlea and Auditory Cortex of a Mouse Model of Age-Related Hearing Loss

2016 ◽  
Vol 21 (5) ◽  
pp. 326-332 ◽  
Author(s):  
Qiuhong Huang ◽  
Hao Xiong ◽  
Haidi Yang ◽  
Yongkang Ou ◽  
Zhigang Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Mouse Model ◽  
Auditory Cortex ◽  
Hair Cells ◽  
Spiral Ganglion ◽  
Outer Hair Cells ◽  
Protective Effects ◽  
Age Related ◽  
Ganglion Neurons ◽  
Age Related Hearing Loss

Bcl-2, the first gene shown to be involved in apoptosis, is a potent regulator of cell survival and known to have protective effects against a variety of age-related diseases. However, the possible relationship between hearing and Bcl-2 expression in the cochlea or auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss, is still unknown. Using RT-PCR, immunohistochemistry, and Western blot analysis, our results show that Bcl-2 is strongly expressed in the inner hair cells and spiral ganglion neurons of young mice. In addition, moderate Bcl-2 expression is also detected in the outer hair cells and in the neurons of the auditory cortex. A significant reduction of Bcl-2 expression in the cochlea or auditory cortex is also associated with elevated hearing thresholds and hair cell loss during aging. The expression pattern of Bcl-2 in the peripheral and central auditory systems suggests that Bcl-2 may play an important role in auditory function serving as a protective molecule against age-related hearing loss.

scholarly journals Noise-induced and age-related hearing loss:  new perspectives and potential therapies

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 927 ◽  
Author(s):  
M Charles Liberman
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Hair Cells ◽  
Auditory Nerve ◽  
Cell Loss ◽  
Sensorineural Hearing ◽  
Hair Cell Loss ◽  
Age Related ◽  
Age Related Hearing Loss

The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a “hidden hearing loss” for two reasons: 1) the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2) the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.

scholarly journals Crystallization of a potassium ion channel and X-ray and neutron data collection

2019 ◽  
Vol 75 (6) ◽  
pp. 435-438 ◽  
Author(s):  
Patricia S. Langan ◽  
Venu Gopal Vandavasi ◽  
Brendan Sullivan ◽  
Joel Harp ◽  
Kevin Weiss ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Potassium Ion ◽  
Potassium Ion Channels ◽  
Potassium Ions ◽  
Potassium Ion Channel ◽  
Neutron Data ◽  
Data Set ◽  
X Ray ◽  
Neutron Diffractometer

The mechanism by which potassium ions are transported through ion channels is currently being investigated by several groups using many different techniques. Clarification of the location of water molecules during transport is central to understanding how these integral membrane proteins function. Neutrons have a unique sensitivity to both hydrogen and potassium, rendering neutron crystallography capable of distinguishing waters from K+ ions. Here, the collection of a complete neutron data set from a potassium ion channel to a resolution of 3.55 Å using the Macromolecular Neutron Diffractometer (MaNDi) is reported. A room-temperature X-ray data set was also collected from the same crystal to a resolution of 2.50 Å. Upon further refinement, these results will help to further clarify the ion/water population within the selectivity filter of potassium ion channels.

scholarly journals miR-153/KCNQ4 axis contributes to noise-induced hearing loss in a mouse model

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Qin Wang ◽  
Wei Li ◽  
Cuiyun Cai ◽  
Peng Hu ◽  
Ruosha Lai
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Broadband Noise ◽  
Hek293 Cells ◽  
Auditory Brainstem Responses ◽  
Luciferase Reporter

AbstractDamage to the cochlear sensory epithelium is a key contributor to noise-induced sensorineural hearing loss (SNHL). KCNQ4 plays an important role in the cochlear potassium circulation and outer hair cells survival. As miR-153 can target and regulate KCNQ4, we sought to study the role of miR-153 in SNHL. 12-week-old male CBA/J mice were exposed to 2–20 kHz broadband noise at 96 dB SPL to induce temporary threshold shifts and 101 dB SPL to induce permanent threshold shifts. Hearing loss was determined by auditory brainstem responses (ABR). Relative expression of miR-153 and KCNQ4 in mice cochlea were determined by Real-Time quantitative PCR. miR-153 mimics were co-transfected with wild type or mutated KCNQ4 into HEK293 cells. Luciferase reporter assay was used to validate the binding between miR-153 and KCNQ4. AAV-sp-153 was constructed and administrated intra-peritoneally 24- and 2-h prior and immediately after noise exposure to knockdown miR-153. The KCNQ4 is mainly expressed in outer hair cells (OHCs). We showed that the expression of KCNQ4 in mice cochlea was reduced and miR-153 expression was significantly increased after noise exposure compared to control. miR-153 bound to 3′UTR of KNCQ4, and the knockdown of miR-153 with the AAV-sp-153 administration restored KCNQ4 mRNA and protein expression. In addition, the knockdown of miR-153 reduced ABR threshold shifts at 8, 16, and 32 kHz after permanent threshold shifts (PTS) noise exposure. Correspondingly, OHC losses were attenuated with inhibition of miR-153. This study demonstrates that miR-153 inhibition significantly restores KNCQ4 in cochlea after noise exposure, which attenuates SNHL. Our study provides a new potential therapeutic target in the prevention and treatment of SNHL.

scholarly journals Occupational Exposure to Noise and Age-related Hearing Loss in an Elderly Population of Southern Italy

2020 ◽  
Vol 13 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Luigi De Maria ◽  
Antonio Caputi ◽  
Rodolfo Sardone ◽  
Enza Sabrina Silvana Cannone ◽  
Francesca Mansi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Occupational Exposure ◽  
Elderly Population ◽  
Noise Exposure ◽  
Exposed Population ◽  
Age Related ◽  
Age Dependent ◽  
Occupationally Exposed ◽  
Age Related Hearing Loss

Background: Age-Related Hearing Loss (ARHL) is a gradual and irreversible age-dependent decline in auditory function. There is still no consensus on the long-term functional effects of noise exposure on ARHL. Objective: This study aimed to compare the prevalence of ARHL in an elderly population occupationally exposed to noise in a non-exposed population. Methods: The population was divided into two groups: a group of 482 subjects professionally exposed to noise for over 10 years and a group of 1129 non-exposed subjects. Among the exposed subjects, a subgroup of 298 who worked for over 10 years in the glassware industry was selected. All the participants underwent a thorough otorhinolaryngological examination. Results: The presence of ARHL was found in 81% of exposed subjects and in 4% of non-exposed subjects. In the sub-group of glassware workers, the prevalence was 88%. The statistical analysis showed a significant association between previous occupational exposure to noise and ARHL (OR = 1.09; 95% CI = 1.067-1.124; p = 0.0012) and between exposure to the glassware industry and ARHL (OR = 1.89; 95% CI = 1.78-1.96; p = 0.006). Conclusion: Consistent with recent studies, we found a significantly higher prevalence of ARHL among workers exposed to noise; however, further studies are needed to support these findings.

scholarly journals Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss

2021 ◽  
Vol 9 ◽  
Author(s):  
Zu-Hong He ◽  
Song Pan ◽  
Hong-Wei Zheng ◽  
Qiao-Jun Fang ◽  
Kayla Hill ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Calcineurin Inhibitor ◽  
Noise Exposure ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Oxygen Species ◽  
Noise Induced Hearing Loss ◽  
Activated T Cells ◽  
Interfering Rna

Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Here we showed that CaN immunolabeling in outer hair cells (OHCs) and nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) in OHC nuclei are significantly increased after moderate noise exposure in adult CBA/J mice. Consequently, treatment with FK506 significantly reduces moderate-noise-induced loss of OHCs and NIHL. Furthermore, induction of reactive oxygen species (ROS) by moderate noise was significantly diminished by treatment with FK506. In agreement with our previous finding that autophagy marker microtubule-associated protein light chain 3B (LC3B) does not change in OHCs under conditions of moderate-noise-induced permanent threshold shifts, treatment with FK506 increases LC3B immunolabeling in OHCs after exposure to moderate noise. Additionally, prevention of NIHL by treatment with FK506 was partially abolished by pretreatment with LC3B small interfering RNA. Taken together, these results indicate that attenuation of moderate-noise-induced OHC loss and hearing loss by FK506 treatment occurs not only via inhibition of CaN activity but also through inhibition of ROS and activation of autophagy.

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