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.

The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in Age-Related Hearing Loss

2017 ◽  
Vol 22 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Qiuhong Huang ◽  
Yongkang Ou ◽  
Hao Xiong ◽  
Haidi Yang ◽  
Zhigang Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Auditory Cortex ◽  
Molecular Mechanisms ◽  
Primary Auditory Cortex ◽  
Auditory Brainstem ◽  
Hearing Ability ◽  
Age Related ◽  
Brainstem Response ◽  
The Central Nervous System ◽  
Age Related Hearing Loss

Hypothesis: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex. Background: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood. Methods: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons. Results: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis. Conclusion: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.

scholarly journals Age-Related Hearing Loss in Mn-SOD Heterozygous Knockout Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Makoto Kinoshita ◽  
Takashi Sakamoto ◽  
Akinori Kashio ◽  
Takahiko Shimizu ◽  
Tatsuya Yamasoba
Keyword(s):  
Hearing Loss ◽  
Manganese Superoxide Dismutase ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Cell Loss ◽  
Auditory Brainstem ◽  
Spiral Ganglion Cell ◽  
Age Related ◽  
Brainstem Response ◽  
Age Related Hearing Loss

Age-related hearing loss (AHL) reduces the quality of life for many elderly individuals. Manganese superoxide dismutase (Mn-SOD), one of the antioxidant enzymes acting within the mitochondria, plays a crucial role in scavenging reactive oxygen species (ROS). To determine whether reduction in Mn-SOD accelerates AHL, we evaluated auditory function in Mn-SOD heterozygous knockout (HET) mice and their littermate wild-type (WT) C57BL/6 mice by means of auditory brainstem response (ABR). Mean ABR thresholds were significantly increased at 16 months when compared to those at 4 months in both WT and HET mice, but they did not significantly differ between them at either age. The extent of hair cell loss, spiral ganglion cell density, and thickness of the stria vascularis also did not differ between WT and HET mice at either age. At 16 months, immunoreactivity of 8-hydroxydeoxyguanosine was significantly greater in the SGC and SV in HET mice compared to WT mice, but that of 4-hydroxynonenal did not differ between them. These findings suggest that, although decrease of Mn-SOD by half may increase oxidative stress in the cochlea to some extent, it may not be sufficient to accelerate age-related cochlear damage under physiological aging process.

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 ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cognitive Function ◽  
Hearing Aids ◽  
Treatment Strategies ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Dependent Manner ◽  
Object Recognition Test ◽  
Age Related ◽  
Age Related Hearing Loss

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.

scholarly journals Effects of enriched endogenous omega-3 fatty acids on age-related hearing loss in mice

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yohei Honkura ◽  
Jun Suzuki ◽  
Nobuyuki Sakayori ◽  
Hitoshi Inada ◽  
Tetsuaki Kawase ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Hearing Loss ◽  
Dietary Intervention ◽  
Auditory Brainstem ◽  
Omega 3 ◽  
Wild Type ◽  
Age Related ◽  
Omega 6 ◽  
Brainstem Response ◽  
Age Related Hearing Loss

Abstract Objective Dietary intervention is a practical prevention strategy for age-related hearing loss (AHL). Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may be effective in prevention of AHL due to their anti-inflammatory and tissue-protective functions. Age-related changes in the hearing function of wild-type and Fat-1 transgenic mice derived from the C57BL/6N strain, which can convert omega-6 PUFAs to n-3 PUFAs and consequently produce enriched endogenous n-3 PUFAs, were investigated to test the efficacy of n-3 PUFAs for AHL prevention. Results At 2 months, the baseline auditory brainstem response (ABR) thresholds were the same in Fat-1 and wild-type mice at 8–16 kHz but were significantly higher in Fat-1 mice at 4 and 32 kHz. In contrast, the ABR thresholds of Fat-1 mice were significantly lower at 10 months. Moreover, the ABR thresholds of Fat-1 mice at low-middle frequencies were significantly lower at 13 months (12 kHz). Body weights were significantly reduced in Fat-1 mice at 13 months, but not at 2, 10, and 16–17 months. In conclusion, enriched endogenous n-3 PUFAs produced due to the expression of the Fat-1 transgene partially alleviated AHL in male C57BL/6N mice.

scholarly journals Age-related changes of auditory brainstem responses in nonhuman primates

2015 ◽  
Vol 114 (1) ◽  
pp. 455-467 ◽  
Author(s):  
Chi-Wing Ng ◽  
Xochi Navarro ◽  
James R. Engle ◽  
Gregg H. Recanzone
Keyword(s):  
Hearing Loss ◽  
Nonhuman Primates ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
High Frequencies ◽  
Age Related ◽  
Wide Range ◽  
Brainstem Response ◽  
Age Related Hearing Loss ◽  
Age Related Changes

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.

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.

scholarly journals Association of Age-Related Hearing Loss with Cognitive Decline

2020 ◽  
Vol 63 (4) ◽  
pp. 145-153
Author(s):  
Juyong Chung
Keyword(s):  
Hearing Loss ◽  
Cognitive Decline ◽  
Cochlear Implants ◽  
Hearing Aids ◽  
Microvascular Disease ◽  
Single Mechanism ◽  
Hearing Aid Use ◽  
Age Related ◽  
Age Related Hearing Loss

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.

scholarly journals INNOVATIVE POLICIES AND TECHNOLOGIES TO INCREASE ACCESS TO HEARING AIDS FOR ADULTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S828-S829
Author(s):  
Michael Yong ◽  
Amber Willink ◽  
Catherine McMahon ◽  
Bradley McPherson ◽  
Carrie L Nieman ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Aids ◽  
Total Population ◽  
Hearing Aid ◽  
Insurance Coverage ◽  
Current State ◽  
Hearing Aid Use ◽  
Age Related ◽  
The World ◽  
Age Related Hearing Loss

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.

scholarly journals Automatic Speech Recognition Predicts Speech Intelligibility and Comprehension for Listeners With Simulated Age-Related Hearing Loss

2017 ◽  
Vol 60 (9) ◽  
pp. 2394-2405 ◽  
Author(s):  
Lionel Fontan ◽  
Isabelle Ferrané ◽  
Jérôme Farinas ◽  
Julien Pinquier ◽  
Julien Tardieu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Speech Recognition ◽  
Automatic Speech Recognition ◽  
Hearing Aids ◽  
Speech Processing ◽  
Fine Tuning ◽  
Language Models ◽  
Age Related ◽  
Age Related Hearing Loss ◽  
Asr System

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.

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