scholarly journals Auditory Threshold Variability in the SAMP8 Mouse Model of Age-Related Hearing Loss: Functional Loss and Phenotypic Change Precede Outer Hair Cell Loss

2021 ◽  
Vol 13 ◽  
Author(s):  
Barbara Peixoto Pinheiro ◽  
Youssef Adel ◽  
Marlies Knipper ◽  
Marcus Müller ◽  
Hubert Löwenheim
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Cell Loss ◽  
Hair Cell Loss ◽  
Auditory Function ◽  
Phenotypic Changes ◽  
Age Related ◽  
Age Related Hearing Loss ◽  
Samp8 Mice

Age-related hearing loss (ARHL) is the most common sensory deficit in aging society, which is accompanied by increased speech discrimination difficulties in noisy environments, social isolation, and cognitive decline. The audiometric degree of ARHL is largely correlated with sensory hair cell loss in addition to age-related factors not captured by histopathological analysis of the human cochlea. Previous studies have identified the senescence-accelerated mouse prone strain 8 (SAMP8) as a model for studying ARHL and age-related modifications of the cochlear redox environment. However, the SAMP8 population exhibits a large variability in auditory function decline over age, whose underlying cause remains unknown. In this study, we analyzed auditory function of SAMP8 mice by measuring auditory brainstem response (ABR) thresholds at the age of 6 weeks (juvenile), 12 weeks (young adult), and 24 weeks (adult). Consistent with previous studies, SAMP8 mice exhibit an early progressive, age-related decline of hearing acuity. However, a spatiotemporal cytohistological analysis showed that the significant increase in threshold variability was not concurrently reflected in outer hair cell (OHC) loss observed in the lower and upper quartiles of the ABR threshold distributions over age. This functional loss was found to precede OHC loss suggesting that age-related phenotypic changes may be contributing factors not represented in cytohistological analysis. The expression of potassium channels KCNQ4 (KV7.4), which mediates the current IK,n crucial for the maintenance of OHC membrane potential, and KCNQ1 (KV7.1), which is an essential component in potassium circulation and secretion into the endolymph generating the endocochlear potential, showed differences between these quartiles and age groups. This suggests that phenotypic changes in OHCs or the stria vascularis due to variable oxidative deficiencies in individual mice may be predictors of the observed threshold variability in SAMP8 mice and their progressive ARHL. In future studies, further phenotypic predictors affected by accumulated metabolic challenges over age need to be investigated as potentially underlying causes of ARHL preceding irreversible OHC loss in the SAMP8 mouse model.

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.

A DPOAE assessment of outer hair cell integrity in ears with age-related hearing loss

2016 ◽  
Vol 332 ◽  
pp. 137-150 ◽  
Author(s):  
Margarete A. Ueberfuhr ◽  
Hannah Fehlberg ◽  
Shawn S. Goodman ◽  
Robert H. Withnell
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Cell Integrity ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Richard A. Altschuler ◽  
Lisa Kabara ◽  
Catherine Martin ◽  
Ariane Kanicki ◽  
Courtney E. Stewart ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Control Diet ◽  
Cell Loss ◽  
Diet Group ◽  
Age Related ◽  
Significant Difference ◽  
Basal Half ◽  
And Control

Our previous study demonstrated rapamycin added to diet at 4 months of age had significantly less age-related outer hair cell loss in the basal half of the cochlea at 22 months of age compared to mice without rapamycin. The present study tested adding rapamycin to diet later in life, at 14 months of age, and added a longitudinal assessment of auditory brain stem response (ABR). The present study used UMHET4 mice, a 4 way cross in which all grandparental strains lack the Cdh23753A allele that predisposes to early onset, progressive hearing loss. UMHET4 mice typically have normal hearing until 16–17 months, then exhibit threshold shifts at low frequencies/apical cochlea and later in more basal high frequency regions. ABR thresholds at 4, 12, 24, and 48 kHz were assessed at 12, 18, and 24 months of age and compared to baseline ABR thresholds acquired at 5 months of age to determine threshold shifts (TS). There was no TS at 12 months of age at any frequency tested. At 18 months of age mice with rapamycin added to diet at 14 months had a significantly lower mean TS at 4 and 12 kHz compared to mice on control diet with no significant difference at 24 and 48 kHz. At 24 months of age, the mean 4 kHz TS in rapamycin diet group was no longer significantly lower than the control diet group, while the 12 kHz mean remained significantly lower. Mean TS at 24 and 48 kHz in the rapamycin diet group became significantly lower than in the control diet group at 24 months. Hair cell counts at 24 months showed large loss in the apical half of most rapamycin and control diet mice cochleae with no significant difference between groups. There was only mild outer hair cell loss in the basal half of rapamycin and control diet mice cochleae with no significant difference between groups. The results show that a later life addition of rapamycin can decrease age-related hearing loss in the mouse model, however, it also suggests that this decrease is a delay/deceleration rather than a complete prevention.

Round Window Application of D-Methionine Provides Complete Cisplatin Otoprotection

2002 ◽  
Vol 126 (6) ◽  
pp. 683-689 ◽  
Author(s):  
Kurtis D. Korver ◽  
Leonard P. Rybak ◽  
Craig Whitworth ◽  
Kathleen M. Campbell
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Round Window ◽  
Organ Of Corti ◽  
Cell Loss ◽  
Auditory Brainstem Responses ◽  
Round Window Membrane ◽  
Hair Cell Loss ◽  
Minute Amount

OBJECTIVE: Cisplatin is a widely used, very effective chemotherapeutic agent that can cause severe ototoxicity. In this study, D-methionine was tested as an otoprotectant via round window membrane (RWM) application in the chinchilla. METHODS: A minute amount of cisplatin alone, or D-methionine followed by cisplatin, was applied topically directly to the intact RWM of anesthetized adult chinchillas. Auditory brainstem responses were measured before and 1 week after topical round window application. Animals were killed, and the cochleas were examined. RESULTS: The ears pretreated with D-methionine were completely protected from hearing loss and hair cell loss in the organ of Corti compared with controls. The ears receiving cisplatin without D-methionine protection sustained nearly complete hearing loss with threshold shifts of >60 dB, with extensive outer hair cell loss throughout the organ of Corti but particularly in the basal turn. CONCLUSION: These results demonstrate that topical D-methionine provides excellent otoprotection against cisplatin-induced ototoxicity both electrophysiologically and structurally.

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 Relation between outer hair cell loss and hearing loss in rats exposed to styrene

2008 ◽  
Vol 243 (1-2) ◽  
pp. 28-34 ◽  
Author(s):  
Guang-Di Chen ◽  
Chiemi Tanaka ◽  
Donald Henderson
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Outer Hair Cell ◽  
Cell Loss ◽  
Hair Cell Loss

Development of Hearing Loss in Kanamycin Treated Chinchillas

1977 ◽  
Vol 86 (2) ◽  
pp. 176-182 ◽  
Author(s):  
Allen Ryan ◽  
Therese J. McGee
Keyword(s):  
Hearing Loss ◽  
Drug Treatment ◽  
Hair Cell ◽  
High Frequency ◽  
Outer Hair Cell ◽  
Cell Loss ◽  
Daily Administration ◽  
Hair Cell Loss ◽  
Kanamycin Sulfate ◽  
Basal Portion

Behaviorally determined auditory theresholds of chinchillas were monitored before, during and after daily administration of kanamycin sulfate (200 mg/kg per day). Drug treatment was terminated as soon as a shift in high-frequency thresholds was observed. In surviving animals, hearing loss spread toward lower frequencies and stabilized after eight to nine days. The stable hearing loss was limited, on the average, to frequencies above 3 kHz. The magnitude of the loss was constant across affected frequencies and averaged about 40 dB. Virtually complete outer hair cell loss was seen in the basal portion of the cochleae of all surviving animals.

scholarly journals Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice

PLoS ONE ◽  
2015 ◽  
Vol 10 (12) ◽  
pp. e0145428 ◽  
Author(s):  
Mary Ann Cheatham ◽  
Roxanne M. Edge ◽  
Kazuaki Homma ◽  
Emily L. Leserman ◽  
Peter Dallos ◽  
...  
Keyword(s):  
Hair Cell ◽  
Cell Survival ◽  
Outer Hair Cell ◽  
Cell Loss ◽  
Hair Cell Loss
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