scholarly journals Inner ear pathology and loss of hearing in estrogen receptor-β deficient mice

2009 ◽  
Vol 201 (3) ◽  
pp. 397-406 ◽  
Author(s):  
Rusana Simonoska ◽  
Annika E Stenberg ◽  
Maoli Duan ◽  
Konstantin Yakimchuk ◽  
Anders Fridberger ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inner Ear ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Auditory Brainstem ◽  
Estrogen Receptor Β ◽  
Knock Out ◽  
Age Related ◽  
Brainstem Response ◽  
Knock Out Mice

There are well known differences between males and females in hearing. In the present study, the role of estrogen receptor-β (ER-β; listed as ESR2 in the MGI Database) in hearing was investigated by comparing hearing and morphology of the inner ear in ER-β knock-out mice (ER-β−/−) with that of wild-type (WT) littermates. Hearing was analyzed with auditory brainstem response audiometry at 3 and 12 months. The ER-β−/− mice were deaf at 1 year of age, and the morphological analysis showed absence of hair cells and loss of the whole organ of Corti initiated in the basal turn of the cochlea. Furthermore, in ER-β−/−, but not in WT mice, the spiral ganglion was lacking many of its neurons. Immunostaining showed the presence of both ER-α (listed as ESR1 in the MGI Database) and ER-β in the nuclei of some neurons in the inner ear in WT mice, but no ER-β was found in the ER-β−/− mice as expected. ER-α staining was predominant in the nuclei of large neurons and ER-β in nuclei of small neurons and fibroblasts. These results reveal that both ERs are present in the inner ear at specific localizations suggesting subtype-specific functions. It is concluded that ER-β is important for the prevention of age-related hearing loss. These findings strengthen the hypothesis that estrogen has a direct effect on hearing functions.

scholarly journals Cisplatin-Induced Ototoxicity in Rats Is Driven by RIP3-Dependent Necroptosis

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 409 ◽  
Author(s):  
Mi-Jin Choi ◽  
Hyunsook Kang ◽  
Yun Yeong Lee ◽  
Oak-Sung Choo ◽  
Jeong Hun Jang ◽  
...  
Keyword(s):  
Cell Death ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Auditory Brainstem ◽  
Sprague Dawley ◽  
Western Blots ◽  
Brainstem Response ◽  
Ganglion Neurons

Cisplatin-induced early-onset ototoxicity is linked to hearing loss. The mechanism by which cisplatin causes ototoxicity remains unclear. The purpose of this study was to identify the involvement of receptor-interacting protein kinase (RIP)3-dependent necroptosis in cisplatin-induced ototoxicity in vitro and in vivo. Sprague–Dawley rats (SD, 8 week) were treated via intraperitoneal (i.p.) injection with cisplatin (16 mg/kg for 1 day), and their hearing thresholds were measured by the auditory brainstem response (ABR) method. Hematoxylin and eosin (H & E) staining, immunohistochemistry, and western blots were performed to determine the effect of cisplatin-induced ototoxicity on cochlear morphology. Inhibitor experiments with necrostatin 1 (Nec-1) and Z-VAD were also performed in HEI-OC1 cell line. H&E stains revealed that the necroptotic changes were increased in the organ of Corti (OC) and spiral ganglion neurons (SGNs). Moreover, immunohistochemistry and western blot analysis showed that cisplatin treatment increased the protein levels of RIP3 in both OCs and SGNs. The treatment of Nec-1, a selective RIP1 inhibitor, resulted in markedly suppression of cisplatin-induced cell death in HEI-OC1 cells, whereas Z-VAD treatment did not change the cisplatin-induced cell death. Our results suggest that RIP3-dependent necroptosis was substantial in cisplatin-induced ototoxicity; inner cochlear regions, the OCs, and SGNs were especially sensitive to necroptosis.

scholarly journals Anti-PD-1 Therapy Does Not Influence Hearing Ability in the Most Sensitive Frequency Range, but Mitigates Outer Hair Cell Loss in the Basal Cochlear Region

2020 ◽  
Vol 21 (18) ◽  
pp. 6701
Author(s):  
Judit Szepesy ◽  
Gabriella Miklós ◽  
János Farkas ◽  
Dániel Kucsera ◽  
Zoltán Giricz ◽  
...  
Keyword(s):  
Outer Hair Cell ◽  
Checkpoint Inhibitors ◽  
Spiral Ganglion ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Antibody Treatment ◽  
High Frequency Region ◽  
Age Related ◽  
Brainstem Response ◽  
Ganglion Neurons

The administration of immune checkpoint inhibitors (ICIs) often leads to immune-related adverse events. However, their effect on auditory function is largely unexplored. Thorough preclinical studies have not been published yet, only sporadic cases and pharmacovigilance reports suggest their significance. Here we investigated the effect of anti-PD-1 antibody treatment (4 weeks, intraperitoneally, 200 μg/mouse, 3 times/week) on hearing function and cochlear morphology in C57BL/6J mice. ICI treatment did not influence the hearing thresholds in click or tone burst stimuli at 4–32 kHz frequencies measured by auditory brainstem response. The number and morphology of spiral ganglion neurons were unaltered in all cochlear turns. The apical-middle turns (<32 kHz) showed preservation of the inner and outer hair cells (OHCs), whilst ICI treatment mitigated the age-related loss of OHCs in the basal turn (>32 kHz). The number of Iba1-positive macrophages has also increased moderately in this high frequency region. We conclude that a 4-week long ICI treatment does not affect functional and morphological integrity of the inner ear in the most relevant hearing range (4–32 kHz; apical-middle turns), but a noticeable preservation of OHCs and an increase in macrophage activity appeared in the >32 kHz basal part of the cochlea.

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.

Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity

2012 ◽  
Vol 126 (11) ◽  
pp. 1091-1096 ◽  
Author(s):  
M Topdag ◽  
M Iseri ◽  
E Gelenli ◽  
M Yardimoglu ◽  
Y Yazir ◽  
...  
Keyword(s):  
Auditory Brainstem Response ◽  
Stria Vascularis ◽  
Spiral Ganglion ◽  
Organ Of Corti ◽  
Auditory Brainstem ◽  
Prevention And Treatment ◽  
Brainstem Response ◽  
Cellular Apoptosis ◽  
Intratympanic Dexamethasone ◽  
Response Testing

AbstractObjective:This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals.Material and methods:This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats.Results:Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p < 0.05). Although piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05).Conclusion:Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

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.

Role of Electrically Evoked Auditory Brainstem Response in Cochlear Implantation of Children With Inner Ear Malformations

2008 ◽  
Vol 29 (5) ◽  
pp. 626-634 ◽  
Author(s):  
Ana H. Kim ◽  
Paul R. Kileny ◽  
H. Alexander Arts ◽  
Hussam K. El-Kashlan ◽  
Steven A. Telian ◽  
...  
Keyword(s):  
Inner Ear ◽  
Cochlear Implantation ◽  
Auditory Brainstem Response ◽  
Auditory Brainstem ◽  
Inner Ear Malformations ◽  
Ear Malformations ◽  
Brainstem Response

scholarly journals Age-Related Changes in the Auditory Brainstem Response and Suprathreshold Processing of Temporal and Spectral Modulation

2019 ◽  
Vol 23 ◽  
pp. 233121651983961 ◽  
Author(s):  
John H. Grose ◽  
Emily Buss ◽  
Hollis Elmore
Keyword(s):  
Auditory Brainstem Response ◽  
Background Noise ◽  
Auditory Brainstem ◽  
Temporal Modulation ◽  
Amplitude Ratios ◽  
Spectral Modulation ◽  
Age Related ◽  
Brainstem Response ◽  
Modulation Detection ◽  
Hearing Difficulties

The purpose of this study was to determine whether cochlear synaptopathy can be shown to be a viable basis for age-related hearing difficulties in humans and whether it manifests as deficient suprathreshold processing of temporal and spectral modulation. Three experiments were undertaken evaluating the effects of age on (a) the auditory brainstem response as a function of level, (b) temporal modulation detection as a function of level and background noise, and (c) spectral modulation as a function of level. Across the three experiments, a total of 21 older listeners with near-normal audiograms and 29 young listeners with audiometrically normal hearing participated. The auditory brainstem response experiment demonstrated reduced Wave I amplitudes and concomitant reductions in the amplitude ratios of Wave I to Wave V in the older listener group. These findings were interpreted as consistent with an electrophysiological profile of cochlear synaptopathy. The temporal and spectral modulation detection experiments, however, provided no support for the hypothesis of compromised suprathreshold processing in these domains. This pattern of results suggests that even if cochlear synaptopathy can be shown to be a viable basis for age-related hearing difficulties, then temporal and spectral modulation detection paradigms are not sensitive to its presence.

Age-related differences in MK-801 induced behaviors in dopamine D3 receptor knock out mice

2010 ◽  
Vol 627 (1-3) ◽  
pp. 177-184
Author(s):  
Alex V. Iarkov ◽  
Terry C. Der ◽  
Jeffrey N. Joyce
Keyword(s):  
Dopamine D3 Receptor ◽  
D3 Receptor ◽  
Knock Out ◽  
Mk 801 ◽  
Age Related ◽  
Dopamine D3 ◽  
Knock Out Mice
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