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

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22062853 ◽

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.

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

Audiology and Neurotology ◽

10.1159/000454874 ◽

2017 ◽

Vol 22 (2) ◽

pp. 96-103 ◽

Cited By ~ 4

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.

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Oxidative Stresses and Mitochondrial Dysfunction in Age-Related Hearing Loss

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/582849 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 69

Author(s):

Chisato Fujimoto ◽

Tatsuya Yamasoba

Keyword(s):

Hearing Loss ◽

Mitochondrial Dysfunction ◽

Stria Vascularis ◽

Spiral Ganglion ◽

Organ Of Corti ◽

The Elderly ◽

Laboratory Animals ◽

Age Related ◽

Ganglion Neurons ◽

Age Related Hearing Loss

Age-related hearing loss (ARHL), the progressive loss of hearing associated with aging, is the most common sensory disorder in the elderly population. The pathology of ARHL includes the hair cells of the organ of Corti, stria vascularis, and afferent spiral ganglion neurons as well as the central auditory pathways. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Mitochondria play a crucial role in the induction of intrinsic apoptosis in cochlear cells. ARHL can be prevented in laboratory animals by certain interventions, such as caloric restriction and supplementation with antioxidants. In this review, we will focus on previous research concerning the role of the oxidative stress and mitochondrial dysfunction in the pathology of ARHL in both animal models and humans and introduce concepts that have recently emerged regarding the mechanisms of the development of ARHL.

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Age‐related hearing loss in C57B1/6 mice and the auditory brainstem response

The Journal of the Acoustical Society of America ◽

10.1121/1.2022001 ◽

1984 ◽

Vol 76 (S1) ◽

pp. S73-S73

Author(s):

Kelly Paris‐Hunter ◽

James F. Willott

Keyword(s):

Hearing Loss ◽

Auditory Brainstem Response ◽

Auditory Brainstem ◽

Age Related ◽

Brainstem Response ◽

Age Related Hearing Loss

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Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

Aging ◽

10.18632/aging.101045 ◽

2016 ◽

Vol 8 (9) ◽

pp. 2081-2099 ◽

Cited By ~ 33

Author(s):

Robert D. Frisina ◽

Bo Ding ◽

Xiaoxia Zhu ◽

Joseph P. Walton

Keyword(s):

Hearing Loss ◽

Spiral Ganglion ◽

Cell Loss ◽

Spiral Ganglion Neurons ◽

Loss Prevention ◽

Age Related ◽

Ganglion Neurons ◽

Age Related Hearing Loss

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

BMC Research Notes ◽

10.1186/s13104-019-4809-8 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 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.

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Age-related changes of auditory brainstem responses in nonhuman primates

Journal of Neurophysiology ◽

10.1152/jn.00663.2014 ◽

2015 ◽

Vol 114 (1) ◽

pp. 455-467 ◽

Cited By ~ 14

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics13071041 ◽

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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Noise-induced and age-related hearing loss: new perspectives and potential therapies

F1000Research ◽

10.12688/f1000research.11310.1 ◽

2017 ◽

Vol 6 ◽

pp. 927 ◽

Cited By ~ 78

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.

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