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

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

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.

Presbyacusis and the Auditory Brainstem Response

2002 ◽  
Vol 45 (6) ◽  
pp. 1249-1261 ◽  
Author(s):  
Flint A. Boettcher
Keyword(s):  
Hearing Loss ◽  
Auditory System ◽  
Auditory Brainstem Response ◽  
Animal Studies ◽  
Auditory Brainstem ◽  
Clinical Tool ◽  
Age Related ◽  
Brainstem Response ◽  
Auditory Functions ◽  
Age Related Changes

Age-related hearing loss (ARHL or presbyacusis) is an increasingly common form of sensorineural hearing loss (SNHL) as a result of changing demographics, and the auditory brainstem response (ABR) is a common experimental and clinical tool in audiology and neurology. Some of the changes that occur in the aging auditory system may significantly influence the interpretation of the ABR in comparison to the ABRs of younger adults. The approach of this review will be to integrate physiological and histopathological data from human and animal studies to provide a better understanding of the array of age-related changes in the ABR and to determine how age-related changes in the auditory system may influence how the ABR should be interpreted in presbyacusis. Data will be described in terms of thresholds, latencies, and amplitudes, as well as more complex auditory functions such as masking and temporal processing. Included in the review of data will be an attempt to differentiate between age-related effects that may strictly be due to threshold elevation from those that may be due to the aging process.

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 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 Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xi Gu ◽  
Daqi Wang ◽  
Zhijiao Xu ◽  
Jinghan Wang ◽  
Luo Guo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Protective Effect ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Auditory Brainstem Response ◽  
Gene Editing ◽  
Auditory Brainstem ◽  
Sensorineural Hearing ◽  
Brainstem Response

Abstract Background Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection. Results The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz. Conclusions These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

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