scholarly journals Attenuation of Progressive Hearing Loss in a Model of Age-related Hearing Loss by a Heat Shock Protein Inducer, Geranylgeranylacetone

2010 ◽  
Vol 59 (4) ◽  
pp. 153-160
Author(s):  
Takefumi MIKURIYA
Keyword(s):  
Hearing Loss ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Progressive Hearing Loss ◽  
Age Related ◽  
Age Related Hearing Loss ◽  
Heat Shock Protein Inducer

Attenuation of progressive hearing loss in a model of age-related hearing loss by a heat shock protein inducer, geranylgeranylacetone

2008 ◽  
Vol 1212 ◽  
pp. 9-17 ◽  
Author(s):  
Takefumi Mikuriya ◽  
Kazuma Sugahara ◽  
Kazutaka Sugimoto ◽  
Mitsuaki Fujimoto ◽  
Tsuyoshi Takemoto ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Progressive Hearing Loss ◽  
Age Related ◽  
Age Related Hearing Loss ◽  
Heat Shock Protein Inducer

scholarly journals THOC1 deficiency leads to late-onset nonsyndromic hearing loss through p53-mediated hair cell apoptosis

2019 ◽  
Author(s):  
Luping Zhang ◽  
Yu Gao ◽  
Ru Zhang ◽  
Feifei Sun ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Cell Apoptosis ◽  
Late Onset ◽  
Nonsyndromic Hearing Loss ◽  
Progressive Hearing Loss ◽  
Age Related ◽  
Age Related Hearing Loss ◽  
Shed Light

AbstractApoptosis of cochlear hair cells is a key step towards age-related hearing loss. Although numerous genes have been implicated in the genetic causes of late-onset, progressive hearing loss, few show direct links to the proapoptotic process. By genome-wide linkage analysis and whole exome sequencing, we identified a heterozygous p.L183V variant in THOC1 as the probable cause of the late-onset, progressive, non-syndromic hearing loss in a large dominant family. Thoc1, a member of the conserved multisubunit THO/TREX ribonucleoprotein complex, is highly expressed in mouse and zebrafish hair cells. The Thoc1 mutant zebrafish generated by gRNA-Cas9 system lacks the C-startle response, indicative of the hearing dysfunction. Both Thoc1 mutant and knockdown zebrafish have greatly reduced hair cell numbers, while the latter can be rescued by embryonic microinjection of human wild-type THOC1 mRNA but to significantly lesser degree by the p.L183V mutant mRNA. The Thoc1 deficiency resulted in marked apoptosis in zebrafish hair cells. Consistently, transcriptome sequencing of the mutants showed significantly increased gene expression in the p53-associated signaling pathway. Depletion of p53 or applying the p53 inhibitor Pifithrin-α significantly rescued the hair cell loss in the Thoc1 knockdown zebrafish. Our results suggested that THOC1 deficiency lead to late-onset, progressive hearing loss through p53-mediated hair cell apoptosis. This is to our knowledge the first human disease associated with THOC1 mutations and may shed light on the molecular mechanism underlying the age-related hearing loss.Significance StatementFor the first time, we found that THOC1 deficiency leads to late-onset nonsyndromic hearing loss. Furthermore, we revealed the hypomorphic THOC1 induced p53-mediated hair cell apoptosis. This is to our knowledge the first human disease associated with THOC1 mutations and may shed light on the molecular mechanism underlying the age-related hearing loss.

Risk Factors of Age-related Hearing Loss, Adults over 65 Years in Korea: Including the Effect of the War Participation

2016 ◽  
Vol 17 (2) ◽  
pp. 68-73
Author(s):  
Dong-Wook Kim ◽  
Tae-Young Lee ◽  
Da-Hye Choi ◽  
Taek-Yeong Kim ◽  
Hyun-Chul Moon
Keyword(s):  
Risk Factors ◽  
Hearing Loss ◽  
Age Related ◽  
Age Related Hearing Loss

scholarly journals Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice

2021 ◽  
Vol 22 (6) ◽  
pp. 2853
Author(s):  
Judit Szepesy ◽  
Viktória Humli ◽  
János Farkas ◽  
Ildikó Miklya ◽  
Júlia Tímár ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Aids ◽  
Dose Range ◽  
Auditory Brainstem ◽  
High Frequency Hearing Loss ◽  
Age Related ◽  
Hearing Function ◽  
Brainstem Response ◽  
Aging Societies ◽  
Age Related Hearing Loss

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15–45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.

scholarly journals Reduced resting state functional connectivity with increasing age-related hearing loss and McGurk susceptibility

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alina Schulte ◽  
Christiane M. Thiel ◽  
Anja Gieseler ◽  
Maike Tahden ◽  
Hans Colonius ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Functional Connectivity ◽  
Resting State ◽  
Mcgurk Effect ◽  
Functional Coupling ◽  
Resting State Functional Connectivity ◽  
Visual Integration ◽  
Age Related ◽  
Hearing Thresholds ◽  
Age Related Hearing Loss

Abstract Age-related hearing loss has been related to a compensatory increase in audio-visual integration and neural reorganization including alterations in functional resting state connectivity. How these two changes are linked in elderly listeners is unclear. The current study explored modulatory effects of hearing thresholds and audio-visual integration on resting state functional connectivity. We analysed a large set of resting state data of 65 elderly participants with a widely varying degree of untreated hearing loss. Audio-visual integration, as gauged with the McGurk effect, increased with progressing hearing thresholds. On the neural level, McGurk illusions were negatively related to functional coupling between motor and auditory regions. Similarly, connectivity of the dorsal attention network to sensorimotor and primary motor cortices was reduced with increasing hearing loss. The same effect was obtained for connectivity between the salience network and visual cortex. Our findings suggest that with progressing untreated age-related hearing loss, functional coupling at rest declines, affecting connectivity of brain networks and areas associated with attentional, visual, sensorimotor and motor processes. Especially connectivity reductions between auditory and motor areas were related to stronger audio-visual integration found with increasing hearing loss.

scholarly journals Sex Differences in the Triad of Acquired Sensorineural Hearing Loss

2021 ◽  
Vol 22 (15) ◽  
pp. 8111
Author(s):  
Kuang-Hsu Lien ◽  
Chao-Hui Yang
Keyword(s):  
Hearing Loss ◽  
Sex Differences ◽  
Sexual Dimorphism ◽  
Sensorineural Hearing Loss ◽  
Hormone Replacement ◽  
Modern Society ◽  
Sensorineural Hearing ◽  
Drug Induced ◽  
Age Related ◽  
Age Related Hearing Loss

The triad of noise-generated, drug-induced, and age-related hearing loss is the major cause of acquired sensorineural hearing loss (ASNHL) in modern society. Although these three forms of hearing loss display similar underlying mechanisms, detailed studies have revealed the presence of sex differences in the auditory system both in human and animal models of ASNHL. However, the sexual dimorphism of hearing varies among noise-induced hearing loss (NIHL), ototoxicity, and age-related hearing loss (ARHL). Importantly, estrogen may play an essential role in modulating the pathophysiological mechanisms in the cochlea and several reports have shown that the effects of hormone replacement therapy on hearing loss are complex. This review will summarize the clinical features of sex differences in ASNHL, compare the animal investigations of cochlear sexual dimorphism in response to the three insults, and address how estrogen affects the auditory organ at molecular levels.

scholarly journals A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1041
Author(s):  
Jacqueline Chester ◽  
Edan Johnston ◽  
Daniel Walker ◽  
Melissa Jones ◽  
Corina Mihaela Ionescu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Bile Acid ◽  
Hearing Aids ◽  
Stria Vascularis ◽  
Cellular Damage ◽  
Relevant Evidence ◽  
Neuronal Signalling ◽  
Age Related ◽  
Recent Advancement ◽  
Age Related Hearing Loss

Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s disease, and hearing loss. Age-related hearing loss, also termed presbycusis, is one of the most common sensory impairments worldwide, affecting one in five people over 50 years of age, and this prevalence is growing annually. Associations have emerged between presbycusis and detrimental health outcomes, including social isolation and mental health. It remains largely untreatable apart from hearing aids, and with no globally established prevention strategies in the clinical setting. Hence, this review aims to explore the pathophysiology of presbycusis and potential therapies, based on a recent advancement in bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using the following keywords: presbycusis, drugs, hearing loss, bile acids, nanotechnology, and more than 150 publications were considered directly relevant. Evidence of the multifaceted oxidative stress and chronic inflammation involvement in cellular damage and apoptosis that is associated with a loss of hair cells, damaged and inflamed stria vascularis, and neuronal signalling loss and apoptosis continues to emerge. New robust and effective therapies require drug delivery deeper into the various layers of the cochlea. Bile acid-based nanotechnology has gained wide interest in its permeation-enhancing ability and potential for numerous applications in treating presbycusis.

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