scholarly journals Evaluation of the Effects of Chronic Injection of D-Galactose on Auditory Brainstem Responses as a Model for Studying Age-Related Hearing Loss

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.

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.


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.


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.


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

Author(s):  
Donald M. Caspary ◽  
Daniel A. Llano

As arguably the third most common malady of industrialized populations, age-related hearing loss is associated with social isolation and depression in a subset of the population that will approach 25% by 2050. Development of behavioral or pharmacotherapeutic approaches to prevent or delay the onset of age-related hearing loss and mitigate the impact of hearing loss of speech understanding requires a better understanding of age-related changes that occur in the central auditory processor. This chapter critically reviews and discusses changes that occur in the auditory brainstem and thalamus with increased age. It briefly discusses age-related cellular changes that occur de novo within the central auditory system versus deafferentation plasticity and animal models of aging. Subsections discuss the cochlear nucleus, superior olivary complex, inferior colliculus, and the medial geniculate body with an emphasis on age-related changes in neurotransmission and how these changes could underpin the observed loss of precise temporal processing with increased age.


2017 ◽  
Vol 21 (04) ◽  
pp. 318-322 ◽  
Author(s):  
Pricila Sleifer ◽  
Dayane Didoné ◽  
Ísis Keppeler ◽  
Claudine Bueno ◽  
Rudimar Riesgo

Introduction The tone-evoked auditory brainstem responses (tone-ABR) enable the differential diagnosis in the evaluation of children until 12 months of age, including those with external and/or middle ear malformations. The use of auditory stimuli with frequency specificity by air and bone conduction allows characterization of hearing profile. Objective The objective of our study was to compare the results obtained in tone-ABR by air and bone conduction in children until 12 months, with agenesis of the external auditory canal. Method The study was cross-sectional, observational, individual, and contemporary. We conducted the research with tone-ABR by air and bone conduction in the frequencies of 500 Hz and 2000 Hz in 32 children, 23 boys, from one to 12 months old, with agenesis of the external auditory canal. Results The tone-ABR thresholds were significantly elevated for air conduction in the frequencies of 500 Hz and 2000 Hz, while the thresholds of bone conduction had normal values in both ears. We found no statistically significant difference between genders and ears for most of the comparisons. Conclusion The thresholds obtained by bone conduction did not alter the thresholds in children with conductive hearing loss. However, the conductive hearing loss alter all thresholds by air conduction. The tone-ABR by bone conduction is an important tool for assessing cochlear integrity in children with agenesis of the external auditory canal under 12 months.


Author(s):  
Juan C. Alvarado ◽  
Verónica Fuentes-Santamaría ◽  
María C. Gabaldón-Ull ◽  
José L. Blanco ◽  
José M. Juiz

2017 ◽  
Vol 22 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Qiuhong Huang ◽  
Yongkang Ou ◽  
Hao Xiong ◽  
Haidi Yang ◽  
Zhigang Zhang ◽  
...  

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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