scholarly journals Istradefylline Mitigates Age-Related Hearing Loss in C57BL/6J Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 8000
Author(s):  
Min Shin ◽  
Madhavi Pandya ◽  
Kristan Espinosa ◽  
Ravindra Telang ◽  
Jordi Boix ◽  
...  

Age-related hearing loss (ARHL) is the most common sensory disorder among older people, and yet, the treatment options are limited to medical devices such as hearing aids and cochlear implants. The high prevalence of ARHL mandates the development of treatment strategies that can prevent or rescue age-related cochlear degeneration. In this study, we investigated a novel pharmacological strategy based on inhibition of the adenosine A2A receptor (A2AR) in middle aged C57BL/6 mice prone to early onset ARHL. C57BL/6J mice were treated with weekly istradefylline (A2AR antagonist; 1 mg/kg) injections from 6 to 12 months of age. Auditory function was assessed using auditory brainstem responses (ABR) to tone pips (4–32 kHz). ABR thresholds and suprathreshold responses (wave I amplitudes and latencies) were evaluated at 6, 9, and 12 months of age. Functional outcomes were correlated with quantitative histological assessments of sensory hair cells. Cognitive function was assessed using the Morris water maze and the novel object recognition test, and the zero maze test was used to assess anxiety-like behaviour. Weekly injections of istradefylline attenuated ABR threshold shifts by approximately 20 dB at mid to high frequencies (16–32 kHz) but did not improve ABR suprathreshold responses. Istradefylline treatment improved hair cell survival in a turn-dependent manner, whilst the cognitive function was unaffected by istradefylline treatment. This study presents the first evidence for the rescue potential of istradefylline in ARHL and highlights the role of A2AR in development of age-related cochlear degeneration.

2021 ◽  
Vol 22 (6) ◽  
pp. 2853
Author(s):  
Judit Szepesy ◽  
Viktória Humli ◽  
János Farkas ◽  
Ildikó Miklya ◽  
Júlia Tímár ◽  
...  

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.


2019 ◽  
Author(s):  
Elham Tavanai ◽  
Ghassem Mohammadkhani

The D-galactose induced mimetic aging rat model has been widely used in studies of age-associated diseases recently. Evidence indicates that D-GAL could also play a key role in age-related hearing loss. However, there is conflicting data about the relationship between the D-GAL injection and tone-burst auditory brainstem responses (ABRs). The present study aimed to compare ABRs in D-GAL injected rats compared with young and naturally aged rats. Tone-burst ABR was recorded and analyzed at the frequencies of 4,6,8,12 and 16 kHz in male young (3-month-old, n=10), naturally aging (18-month-old, n=10) and D-GAL injected (3-month-old, 500 mg/kg D-GAL injection for 8 weeks, n=10) Wistar rats. When the ABRs thresholds obtained in the D-GAL group and the natural aging group were compared with the thresholds in the young group, we observed a significant increase in thresholds, which affected all of the frequencies (P<0.05). A statistically significant decrease in amplitude of wave PI at 4 and 8 kHz, PII at 4,8 kHz, PIV at 4,6,8,12 and 16 kHz was also observed in naturally aging group compared with young group. However, in D-GAL group, a significant difference was exclusively detected in amplitude of PIII at 4 kHz. Latency did not reveal any significant difference between the groups (P>0.05). The present study confirmed that experimental injection of 500 mg/kg/day D-GAL for 8 weeks to Wistar rats could lead to ABRs threshold shifts but not latency. Because there are several types of presbycusis, further studies are needed to determine what type of presbycusis is induced by D-GAL and where is the first region affected by it to provide the best treatment and prevention methods. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(5):281-288.


2015 ◽  
Vol 114 (1) ◽  
pp. 455-467 ◽  
Author(s):  
Chi-Wing Ng ◽  
Xochi Navarro ◽  
James R. Engle ◽  
Gregg H. Recanzone

Nonhuman primates, compared with humans and rodents, have historically been far less used for studies of age-related hearing loss, primarily because of their long life span and high cost of maintenance. Strong similarities in genetics, anatomy, and neurophysiology of the auditory nervous system between humans and monkeys, however, could provide fruitful opportunities to enhance our understanding of hearing loss. The present study used a common, noninvasive technique for testing hearing sensitivity in humans, the auditory brainstem response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys, particularly those above 21.5 yr of age, had missing ABR waveforms at high frequencies. Regression analyses revealed that ABR threshold increased as a function of age at peaks II and IV simultaneously. In the suprathreshold hearing condition (70 dB peak sound pressure level), ABR-based audiograms similarly varied as a function of age such that old monkeys had smaller peak amplitudes and delayed latencies at low, middle, and high frequencies. Peripheral hearing differences remained a major influence associated with age-related changes in audiometric functions of old monkeys at a comparable sensation level across animals. The present findings suggest that hearing loss occurs in old monkeys across a wide range of frequencies and that these deficits increase in severity with age. Parallel to prior studies in monkeys, we found weak effects of sex on hearing, and future investigations are necessary to clarify its role in age-related hearing loss.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1041
Author(s):  
Jacqueline Chester ◽  
Edan Johnston ◽  
Daniel Walker ◽  
Melissa Jones ◽  
Corina Mihaela Ionescu ◽  
...  

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.


Author(s):  
Juyong Chung

A number of studies have demonstrated a significant association between age-related hearing loss (ARHL) and cognitive decline. However their relationship is not clear. In this review, we focused on the etiological mechanisms between ARHL and cognitive decline to explain the nature of this relationship: 1) causal mechanisms (e.g., cognitive load hypothesis, cascade hypothesis); 2) common cause mechanisms (e.g., microvascular disease); 3) overdiagnosis or harbinger hypothesis. We conclude that no single mechanism is sufficient and hearing and cognition related to each other in several different ways. In addition, we reviewed the effectiveness of hearing intervention (e.g., hearing aids and cochlear implants) on cognition function, and the role of hearing aid use and cochlear implant depends on the relevant mechanism.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S828-S829
Author(s):  
Michael Yong ◽  
Amber Willink ◽  
Catherine McMahon ◽  
Bradley McPherson ◽  
Carrie L Nieman ◽  
...  

Abstract As the proportion of older adults in the world’s total population continues to grow, the deleterious downstream health economic outcomes of age-related hearing loss are steadily becoming more prevalent. While recent research has shown that age-related hearing loss is the single greatest modifiable risk factor for dementia, the rate of hearing aid use remains low in many countries across the globe. Reasons for poor uptake are multifactorial and likely involve a combination of factors, ranging from increasing costs of hearing aid technology to lack of widespread insurance coverage. This paper aims to first identify the current state of hearing aid access across the world using eight representative countries as examples. We then provide recommendations on how to facilitate greater access to hearing aids for consumers by addressing areas in regulation, technology, reimbursement, and workforce.


2017 ◽  
Vol 60 (9) ◽  
pp. 2394-2405 ◽  
Author(s):  
Lionel Fontan ◽  
Isabelle Ferrané ◽  
Jérôme Farinas ◽  
Julien Pinquier ◽  
Julien Tardieu ◽  
...  

Purpose The purpose of this article is to assess speech processing for listeners with simulated age-related hearing loss (ARHL) and to investigate whether the observed performance can be replicated using an automatic speech recognition (ASR) system. The long-term goal of this research is to develop a system that will assist audiologists/hearing-aid dispensers in the fine-tuning of hearing aids. Method Sixty young participants with normal hearing listened to speech materials mimicking the perceptual consequences of ARHL at different levels of severity. Two intelligibility tests (repetition of words and sentences) and 1 comprehension test (responding to oral commands by moving virtual objects) were administered. Several language models were developed and used by the ASR system in order to fit human performances. Results Strong significant positive correlations were observed between human and ASR scores, with coefficients up to .99. However, the spectral smearing used to simulate losses in frequency selectivity caused larger declines in ASR performance than in human performance. Conclusion Both intelligibility and comprehension scores for listeners with simulated ARHL are highly correlated with the performances of an ASR-based system. In the future, it needs to be determined if the ASR system is similarly successful in predicting speech processing in noise and by older people with ARHL.


PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e73622 ◽  
Author(s):  
Kunio Mizutari ◽  
Takehiro Michikawa ◽  
Hideyuki Saito ◽  
Yasuhide Okamoto ◽  
Chieko Enomoto ◽  
...  

2014 ◽  
Vol 361 (1) ◽  
pp. 359-369 ◽  
Author(s):  
Tanika T. Williamson ◽  
Xiaoxia Zhu ◽  
Joseph P. Walton ◽  
Robert D. Frisina

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