scholarly journals Daple deficiency causes hearing loss in adult mice by inducing defects in cochlear stereocilia and apical microtubules

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshiyuki Ozono ◽  
Atsushi Tamura ◽  
Shogo Nakayama ◽  
Elisa Herawati ◽  
Yukiko Hanada ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Critical Role ◽  
Auditory Brainstem ◽  
Hair Bundle ◽  
Basal Region ◽  
Cochlear Hair Cells ◽  
Adult Mice ◽  
Brainstem Response ◽  
Hair Bundles ◽  
Almost All

AbstractThe V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. However, regulation of hair bundle arrangements has not been fully understood. Recently, defects in hair bundle arrangement were reported in postnatal Dishevelled-associating protein (ccdc88c, alias Daple)-deficient mice. In the present study, we found that adult Daple−/− mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In adult Daple−/− mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical role of Daple in hair bundle arrangement through the orchestration of apical microtubule distribution, and thereby in hearing, especially at high frequencies.

scholarly journals Daple deficiency causes hearing loss in adult mice by inducing defects in cochlear stereocilia and apical microtubules

2021 ◽  
Author(s):  
Yoshiyuki Ozono ◽  
Atsushi Tamura ◽  
Shogo Nakayama ◽  
Elisa Herawati ◽  
Yukiko Hanada ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Auditory Brainstem ◽  
Hair Bundle ◽  
Basal Region ◽  
Cochlear Hair Cells ◽  
Adult Mice ◽  
Brainstem Response ◽  
Hair Bundles ◽  
Almost All ◽  
Response Testing

Abstract The V-shaped arrangement of hair bundles on cochlear hair cells is critical for the auditory sensing. However, regulation of hair bundle arrangements is not fully understood. Recently, defects in hair bundle arrangement were reported in postnatal Dishevelled-associating protein (Daple)-deficient mice. Here, we found that adult Daple-/- mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In adult Daple-/- mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical roles of Daple in hair bundle arrangement, through the orchestration of apical microtubule distribution, and thereby in hearing, especially at high frequencies.

Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs

2016 ◽  
Vol 156 (3) ◽  
pp. 543-548 ◽  
Author(s):  
Alan D. Tate ◽  
Patrick J. Antonelli ◽  
Kyle R. Hannabass ◽  
Carolyn O. Dirain
Keyword(s):  
Hearing Loss ◽  
Auditory Brainstem Response ◽  
Guinea Pigs ◽  
Outer Hair Cell ◽  
Auditory Brainstem ◽  
Response Threshold ◽  
Saline Control ◽  
Control Group ◽  
Cochlear Hair Cells ◽  
Brainstem Response

Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

scholarly journals High-purity isolation of bullfrog hair bundles and subcellular and topological localization of constituent proteins.

1991 ◽  
Vol 112 (4) ◽  
pp. 625-640 ◽  
Author(s):  
P G Gillespie ◽  
A J Hudspeth
Keyword(s):  
Plasma Membranes ◽  
Biochemical Characterization ◽  
Membrane Topology ◽  
Hair Bundle ◽  
Nylon Membrane ◽  
Glass Coverslip ◽  
Weak Bases ◽  
Sds Page ◽  
Topological Localization ◽  
Hair Bundles

The small number of hair cells in auditory and vestibular organs severely impedes the biochemical characterization of the proteins involved in mechano-electrical transduction. By developing an efficient and clean "twist-off" method of hair bundle isolation, and by devising a sensitive, nonradioactive method to detect minute quantities of protein, we have partially overcome this limitation and have extensively classified the proteins of the bundles. To isolate hair bundles, we glue the saccular macula of the bullfrog to a glass coverslip, expose the tissue to a molten agarose solution, and allow the agarose to solidify to a firm gel. By rotating the gel disk with respect to the fixed macula, we isolate the hair bundles by shearing them at their mechanically weak bases. The plasma membranes of at least 80% of the stereocilia reseal. To visualize the proteins of the hair bundle, we covalently label them with biotin, separate them by SDS-PAGE, and transfer them to a charged nylon membrane. We can detect less than 500 fg of protein by probing the membrane with streptavidin-alkaline phosphatase and detecting the chemiluminescent product from the hydrolysis of the substrate 3-(4-methoxyspiro-(1,2-dioxetane-3,2'-tricyclo-[3.3.1. 1(3.7)]decan)-4-yl) phenyl phosphate (AMPPD). These techniques reveal a distinct constellation of proteins in and associated with hair bundles. Several proteins, such as calmodulin, calbindin, actin, tubulin, and fimbrin, have previously been described. A second class of proteins in the preparation appears to be derived from extracellular sources. Finally, several heretofore undescribed bundle proteins are identified and characterized by their membrane topology, subcellular localization, and glycosidase and protease sensitivities.

scholarly journals Dual-Specificity Phosphatase 1 (DUSP1) Has a Central Role in Redox Homeostasis and Inflammation in the Mouse Cochlea

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1351
Author(s):  
Jose M. Bermúdez-Muñoz ◽  
Adelaida M. Celaya ◽  
Ángela García-Mato ◽  
Daniel Muñoz-Espín ◽  
Lourdes Rodríguez-de la Rosa ◽  
...  
Keyword(s):  
Gene Knockout ◽  
Critical Role ◽  
Auditory Brainstem ◽  
Sequencing Analysis ◽  
Dual Specificity Phosphatase ◽  
Redox Imbalance ◽  
Cellular Expression ◽  
Dual Specificity ◽  
Brainstem Response ◽  
Ganglion Neurons

Stress-activated protein kinases (SAPK) are associated with sensorineural hearing loss (SNHL) of multiple etiologies. Their activity is tightly regulated by dual-specificity phosphatase 1 (DUSP1), whose loss of function leads to sustained SAPK activation. Dusp1 gene knockout in mice accelerates SNHL progression and triggers inflammation, redox imbalance and hair cell (HC) death. To better understand the link between inflammation and redox imbalance, we analyzed the cochlear transcriptome in Dusp1−/− mice. RNA sequencing analysis (GSE176114) indicated that Dusp1−/− cochleae can be defined by a distinct profile of key cellular expression programs, including genes of the inflammatory response and glutathione (GSH) metabolism. To dissociate the two components, we treated Dusp1−/− mice with N-acetylcysteine, and hearing was followed-up longitudinally by auditory brainstem response recordings. A combination of immunofluorescence, Western blotting, enzymatic activity, GSH levels measurements and RT-qPCR techniques were used. N-acetylcysteine treatment delayed the onset of SNHL and mitigated cochlear damage, with fewer TUNEL+ HC and lower numbers of spiral ganglion neurons with p-H2AX foci. N-acetylcysteine not only improved the redox balance in Dusp1−/− mice but also inhibited cytokine production and reduced macrophage recruitment. Our data point to a critical role for DUSP1 in controlling the cross-talk between oxidative stress and inflammation.

scholarly journals Minimal-invasive enhancement of auditory perception by terahertz wave modulation

2021 ◽  
Author(s):  
Xiaoxuan Tan ◽  
Kaijie Wu ◽  
Shuang Liu ◽  
Chao Chang ◽  
Wei Xiong
Keyword(s):  
Hair Cells ◽  
Sensorineural Deafness ◽  
Auditory Brainstem ◽  
Terahertz Wave ◽  
Minimal Invasive ◽  
Common Disease ◽  
Target Tissue ◽  
Cochlear Hair Cells ◽  
Wave Modulation ◽  
Brainstem Response

Hearing impairment is a common disease affecting a substantial proportion of the global population. Currently, the most effective clinical treatment for patients with sensorineural deafness is to implant an artificial electronic cochlea. However, the improvements to hearing perception are variable and limited among healthy subjects. Moreover, cochlear implants have disadvantages, such as crosstalk derived from the currents that spread into non-target tissue between the electrodes. Here, in this work, we describe terahertz wave modulation (THM), a new, minimally invasive technology that can enhance hearing perception in animals by reversible modulation of currents in cochlear hair cells. Using single-cell electrophysiology, guinea pig audiometry, and molecular dynamics simulations (MD), we show that THM can reversibly increase mechano-electrical transducer (MET)currents (~50% higher) and voltage-gated K+ currents in cochlear hair cells through collective resonance of −C=O groups. In addition, measurement of auditory brainstem response (ABR) in guinea pigs treated with THM indicated a ~10 times increase in hearing sensitivity. This study thus reports a new method of highly spatially selective hearing enhancement without introducing any exogeneous gene, which has potential applications for treatment of hearing disorders as well as several other areas of neuroscience.

Effects of Stimulus Repetition Rates on the Auditory Brainstem Response to Level-Specific CE-Chirp in Normal-Hearing Adults

2020 ◽  
Vol 29 (4) ◽  
pp. 838-850
Author(s):  
Ahmad Aidil Arafat Dzulkarnain ◽  
Fatin Amira Shahrudin ◽  
Fatin Nabilah Jamal ◽  
Muhammad Nasrullah Marzuki ◽  
Mohd Naufal Shah Mazlan
Keyword(s):  
Auditory Brainstem Response ◽  
Auditory Brainstem ◽  
Normal Hearing ◽  
Repeated Measure ◽  
Stimulus Repetition ◽  
Residual Noise ◽  
Brainstem Response ◽  
High Stimulus ◽  
Almost All ◽  
Study Participants

Purpose The purpose of this study is to investigate the influence of stimulus repetition rates on the auditory brainstem response (ABR) to Level-Specific (LS) CE-Chirp and click stimuli at multiple intensity levels in normal-hearing adults. Method A repeated-measure study design was used on 13 normal-hearing adults. ABRs were acquired from the study participants using LS CE-Chirp and click stimuli at four stimulus repetition rates (19.1, 33.3, 61.1, and 81.1 Hz) and four intensity levels (80, 60, 40, and 20 dB nHL). The ABR test was stopped at 40-nV residual noise level. Results High-stimulus repetition rates caused the ABR latencies to be longer and have reduced amplitudes in both ABR to LS CE-Chirp and click stimuli. The ABR to LS CE-Chirp Wave I, III, and V amplitudes were larger than ABR to click in almost all the stimulus repetition rates. However, there were no differences in the number of averages required to reach the stopping criterion between ABR to LS CE-Chirp and click stimulus, and between high-stimulus repetition rates and low-stimulus repetition rates. Conclusion The LS CE-Chirp at standard low-stimulus repetition rates can be used to elicit ABR for both neurodiagnostic and threshold seeking procedure.

scholarly journals Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth

2016 ◽  
Vol 212 (2) ◽  
pp. 231-244 ◽  
Author(s):  
Andrea Lelli ◽  
Vincent Michel ◽  
Jacques Boutet de Monvel ◽  
Matteo Cortese ◽  
Montserrat Bosch-Grau ◽  
...  
Keyword(s):  
Hair Cells ◽  
Late Onset ◽  
Critical Role ◽  
Normal Hearing ◽  
Hair Bundle ◽  
Class Iii ◽  
Auditory Hair Cells ◽  
Mechanoelectrical Transduction ◽  
Hair Bundles ◽  
Myosin Iiia

The precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a−/−Myo3b−/− mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b−/− mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a−/−Myo3b−/− cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a−/−Myo3b−/− stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping.

scholarly journals Activin Signaling Disruption in the Cochlea Does Not Influence Hearing in Adult Mice

2014 ◽  
Vol 20 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Lukas Horvath ◽  
Daniel Bodmer ◽  
Vesna Radojevic ◽  
Arianne Monge Naldi
Keyword(s):  
Auditory Brainstem ◽  
Activin A ◽  
Dominant Negative ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Activin Signaling ◽  
Hearing Ability ◽  
Adult Mice ◽  
Brainstem Response ◽  
Cochlear Morphology

Activin, a member of the TGF-F superfamily, was found to play an important role in the development, repair and apoptosis of different tissues and organs. Accordingly, activin signaling is involved in the development of the cochlea. Activin binds to its receptor ActRII, then dimerizes with ActRI and induces a signaling pathway resulting in gene expression. A study reported a case of fibrodysplasia ossificans progressiva with an unusual mutation in the ActRI gene leading to sensorineural hearing loss. This draws attention to the role of activin and its receptors in the developed cochlea. To date, only the expression of ActRII is known in the adult mammalian cochlea. In this study, we present for the first time the presence of activin A and ActRIB in the adult cochlea. Transgenic mice with postnatal dominant-negative ActRIB expression causing disruption of activin signaling in vivo were used for assessing cochlear morphology and hearing ability through the auditory brainstem response (ABR) threshold. Nonfunctioning ActRIB did not affect the ABR thresholds and did not alter the microscopic anatomy of the cochlea. We conclude, therefore, that activin signaling is not necessary for hearing in adult mice under physiological conditions but may be important during and after damaging events in the inner ear. i 2014 S. Karger AG, Basel

Hit and False-Alarm Rates of Selected ABR Indices in Differentiating Cochlear Disorders From Acoustic Tumors

1996 ◽  
Vol 5 (1) ◽  
pp. 90-96 ◽  
Author(s):  
Frank E. Musiek ◽  
Cynthia A. McCormick ◽  
Raymond M. Hurley
Keyword(s):  
False Alarm ◽  
Amplitude Ratio ◽  
High Specificity ◽  
Auditory Brainstem ◽  
Latency Difference ◽  
Cochlear Pathology ◽  
Brainstem Response ◽  
Absolute Latency ◽  
Two Indices ◽  
Low Sensitivity

We performed a retrospective study of 26 patients with acoustic tumors and 26 patients with otologically diagnosed cochlear pathology to determine the sensitivity (hit rate), specificity (false-alarm rate), and efficiency of six auditory brainstem response indices. In addition, a utility value was determined for each of these six indices. The I–V interwave interval, the interaural latency difference, and the absolute latency of wave V provided the highest hit rates, the best A’ values and good utility. The V/I amplitude ratio index provided high specificity but low sensitivity scores. In regard to sensitivity and specificity, using the combination of two indices provided little overall improvement over the best one-index measures.

The Effect of Kalman-Weighted Averaging and Artifact Rejection on Residual Noise During Auditory Brainstem Response Testing

2019 ◽  
Vol 28 (1) ◽  
pp. 114-124
Author(s):  
Linda W. Norrix ◽  
Julie Thein ◽  
David Velenovsky
Keyword(s):  
Repeated Measures ◽  
Auditory Brainstem ◽  
Weighted Averaging ◽  
Auditory Brainstem Responses ◽  
Residual Noise ◽  
Electrophysiological Recordings ◽  
Artifact Rejection ◽  
Brainstem Response ◽  
Active Motor ◽  
Averaging Time

Purpose Low residual noise (RN) levels are critically important when obtaining electrophysiological recordings of threshold auditory brainstem responses. In this study, we examine the effectiveness and efficiency of Kalman-weighted averaging (KWA) implemented on the Vivosonic Integrity System and artifact rejection (AR) implemented on the Intelligent Hearing Systems SmartEP system for obtaining low RN levels. Method Sixteen adults participated. Electrophysiological measures were obtained using simultaneous recordings by the Vivosonic and Intelligent Hearing Systems for subjects in 2 relaxed conditions and 4 active motor conditions. Three averaging times were used for the relaxed states (1, 1.5, and 3 min) and for the active states (1.5, 3, and 6 min). Repeated-measures analyses of variance were used to examine RN levels as a function of noise reduction strategy (i.e., KWA, AR) and averaging time. Results Lower RN levels were obtained using KWA than AR in both the relaxed and active motor states. Thus, KWA was more effective than was AR under the conditions examined in this study. Using KWA, approximately 3 min of averaging was needed in the relaxed condition to obtain an average RN level of 0.025 μV. In contrast, in the active motor conditions, approximately 6 min of averaging was required using KWA. Mean RN levels of 0.025 μV were not attained using AR. Conclusions When patients are not physiologically quiet, low RN levels are more likely to be obtained and more efficiently obtained using KWA than AR. However, even when using KWA, in active motor states, 6 min of averaging or more may be required to obtain threshold responses. Averaging time needed and whether a low RN level can be attained will depend on the level of motor activity exhibited by the patient.

Sign in / Sign up

Export Citation Format

Share Document