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

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.

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.

Age-Related Hearing Loss: A Loss of Voltage, Not Hair Cells

2006 ◽  
Vol 27 (4) ◽  
pp. 228-236 ◽  
Author(s):  
John Mills ◽  
Richard Schmiedt ◽  
Bradley Schulte ◽  
Judy Dubno
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Deafness and Cochlear Fibrocyte Alterations in Mice Deficient for the Inner Ear Protein Otospiralin

2005 ◽  
Vol 25 (2) ◽  
pp. 847-853 ◽  
Author(s):  
Benjamin Delprat ◽  
Jérôme Ruel ◽  
Matthieu J. Guitton ◽  
Ghyslaine Hamard ◽  
Marc Lenoir ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Unknown Function ◽  
Stria Vascularis ◽  
Type Ii ◽  
Auditory Function ◽  
Age Related ◽  
Cochlear Physiology ◽  
Auditory Organ ◽  
Age Related Hearing Loss

ABSTRACT In the cochlea, the mammalian auditory organ, fibrocytes of the mesenchymal nonsensory regions play important roles in cochlear physiology, including the maintenance of ionic and hydric components in the endolymph. Occurrence of human deafness in fibrocyte alterations underlines their critical roles in auditory function. We recently described a novel gene, Otos, which encodes otospiralin, a small protein of unknown function that is produced by the fibrocytes of the cochlea and vestibule. We now have generated mice with deletion of Otos and found that they show moderate deafness, with no frequency predominance. Histopathology revealed a degeneration of type II and IV fibrocytes, while hair cells and stria vascularis appeared normal. Together, these findings suggest that impairment of fibrocytes caused by the loss in otospiralin leads to abnormal cochlear physiology and auditory function. This moderate dysfunction may predispose to age-related hearing loss.

scholarly journals Codeficiency of Lysosomal Mucolipins 3 and 1 in Cochlear Hair Cells Diminishes Outer Hair Cell Longevity and Accelerates Age-Related Hearing Loss

2018 ◽  
Vol 38 (13) ◽  
pp. 3177-3189 ◽  
Author(s):  
Teerawat Wiwatpanit ◽  
Natalie N. Remis ◽  
Aisha Ahmad ◽  
Yingjie Zhou ◽  
John C. Clancy ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Outer Hair Cell ◽  
Cochlear Hair Cells ◽  
Age Related ◽  
Age Related Hearing Loss ◽  
Cell Longevity

scholarly journals N-acetyl-cysteine prevents age-related hearing loss and the progressive loss of inner hair cells in γ-glutamyl transferase 1 deficient mice

Aging ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 730-750 ◽  
Author(s):  
Dalian Ding ◽  
Haiyan Jiang ◽  
Guang-Di Chen ◽  
Chantal Longo-Guess ◽  
Vijaya Prakash Krishnan Muthaiah ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Inner Hair Cells ◽  
Progressive Loss ◽  
Age Related ◽  
Acetyl Cysteine ◽  
Glutamyl Transferase ◽  
Age Related Hearing Loss ◽  
Deficient Mice

scholarly journals MANF supports the inner hair cell synapse and the outer hair cell stereocilia bundle in the cochlea

2021 ◽  
Vol 5 (2) ◽  
pp. e202101068
Author(s):  
Kuu Ikäheimo ◽  
Anni Herranen ◽  
Vilma Iivanainen ◽  
Tuuli Lankinen ◽  
Antti A Aarnisalo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Er Stress ◽  
Hair Cell ◽  
Hair Cells ◽  
High Frequency ◽  
Outer Hair Cell ◽  
Outer Hair Cells ◽  
Inner Hair Cell ◽  
Age Related ◽  
Er Homeostasis

Failure in the structural maintenance of the hair cell stereocilia bundle and ribbon synapse causes hearing loss. Here, we have studied how ER stress elicits hair cell pathology, using mouse models with inactivation of Manf (mesencephalic astrocyte-derived neurotrophic factor), encoding an ER-homeostasis-promoting protein. From hearing onset, Manf deficiency caused disarray of the outer hair cell stereocilia bundle and reduced cochlear sound amplification capability throughout the tonotopic axis. In high-frequency outer hair cells, the pathology ended in molecular changes in the stereocilia taper region and in strong stereocilia fusion. In high-frequency inner hair cells, Manf deficiency degraded ribbon synapses. The altered phenotype strongly depended on the mouse genetic background. Altogether, the failure in the ER homeostasis maintenance induced early-onset stereociliopathy and synaptopathy and accelerated the effect of genetic causes driving age-related hearing loss. Correspondingly, MANF mutation in a human patient induced severe sensorineural hearing loss from a young age onward. Thus, we present MANF as a novel protein and ER stress as a mechanism that regulate auditory hair cell maintenance in both mice and humans.

c.753A>G genome editing of a Cdh23 allele delays age-related hearing loss and degeneration of cochlear hair cells in C57BL/6J mice

2020 ◽  
Vol 389 ◽  
pp. 107926 ◽  
Author(s):  
Shumpei P. Yasuda ◽  
Yuta Seki ◽  
Sari Suzuki ◽  
Yasuhiro Ohshiba ◽  
Xuehan Hou ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Genome Editing ◽  
Hair Cells ◽  
Cochlear Hair Cells ◽  
Age Related ◽  
Age Related Hearing Loss
Sign in / Sign up

Export Citation Format

Share Document