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https://www.readbyqxmd.com/read/28717876/structural-and-ultrastructural-changes-to-type-i-spiral-ganglion-neurons-and-schwann-cells-in-the-deafened-guinea-pig-cochlea
#1
Andrew K Wise, Remy Pujol, Thomas G Landry, James B Fallon, Robert K Shepherd
Sensorineural hearing loss is commonly caused by damage to cochlear sensory hair cells. Coinciding with hair cell degeneration, the peripheral fibres of type I spiral ganglion neurons (SGNs) that normally form synaptic connections with the inner hair cell gradually degenerate. We examined the time course of these degenerative changes in type I SGNs and their satellite Schwann cells at the ultrastructural level in guinea pigs at 2, 6, and 12 weeks following aminoglycoside-induced hearing loss. Degeneration of the peripheral fibres occurred prior to the degeneration of the type I SGN soma and was characterised by shrinkage of the fibre followed by retraction of the axoplasm, often leaving a normal myelin lumen devoid of axoplasmic content...
July 17, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28713423/discovering-the-unexpected-with-the-utilization-of-ngs-in-diagnostics-of-non-syndromic-hearing-loss-disorders-the-family-case-of-ildr1-dependent-hearing-loss-disorder
#2
Jernej Kovač, Gašper Klančar, Katarina Trebušak Podkrajšek, Saba Battelino
Sensorineural hearing loss (SNHL) is a heterogeneous family of hearing disabilities with congenital (including genetic) as well as acquired etiology. Congenital SNHL of genetic etiology is further sub-divided into autosomal dominant, autosomal recessive and X-linked SNHL. More than 60 genes are involved in the etiology of autosomal recessive non-syndromic hearing loss (ARNSHL) commonly manifesting as heterogeneous pre-lingual profound to severe non-progressive clinical phenotype. ILDR1-dependent ARNSHL (DFNB42, OMIM: # 609646) is a very rare sub-type of hearing disability, with unknown prevalence, caused by function-damaging genetic variants in ILDR1 gene reported in families of Middle-Eastern origin...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28712672/noise-induced-cochlear-synaptopathy-in-rhesus-monkeys-macaca-mulatta
#3
M D Valero, J A Burton, S N Hauser, T A Hackett, R Ramachandran, M C Liberman
Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss...
July 8, 2017: Hearing Research
https://www.readbyqxmd.com/read/28705869/auditory-cortex-interneuron-development-requires-cadherins-operating-hair-cell-mechanoelectrical-transduction
#4
Baptiste Libé-Philippot, Vincent Michel, Jacques Boutet de Monvel, Sébastien Le Gal, Typhaine Dupont, Paul Avan, Christine Métin, Nicolas Michalski, Christine Petit
Many genetic forms of congenital deafness affect the sound reception antenna of cochlear sensory cells, the hair bundle. The resulting sensory deprivation jeopardizes auditory cortex (AC) maturation. Early prosthetic intervention should revive this process. Nevertheless, this view assumes that no intrinsic AC deficits coexist with the cochlear ones, a possibility as yet unexplored. We show here that many GABAergic interneurons, from their generation in the medial ganglionic eminence up to their settlement in the AC, express two cadherin-related (cdhr) proteins, cdhr23 and cdhr15, that form the hair bundle tip links gating the mechanoelectrical transduction channels...
July 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28703809/epigallocatechin-3-gallate-a-prototypic-chemopreventative-agent-for-protection-against-cisplatin-based-ototoxicity
#5
Vikrant Borse, Raheem F H Al Aameri, Kelly Sheehan, Sandeep Sheth, Tejbeer Kaur, Debashree Mukherjea, Srinivasan Tupal, Michelle Lowy, Sumana Ghosh, Asmita Dhukhwa, Puspanjali Bhatta, Leonard P Rybak, Vickram Ramkumar
Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28701711/amplification-mode-differs-along-the-length-of-the-mouse-cochlea-as-revealed-by-connexin-26-deletion-from-specific-gap-junctions
#6
Victoria A Lukashkina, Tetsuji Yamashita, Jian Zuo, Andrei N Lukashkin, Ian J Russell
The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forces delivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters' cells (DCs) and pillar cells (PCs), coupled by gap-junctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knock-out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-driving-voltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28690836/noise-induced-and-age-related-hearing-loss-%C3%A2-new-perspectives-and-potential-therapies
#7
REVIEW
M Charles Liberman
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...
2017: F1000Research
https://www.readbyqxmd.com/read/28689068/efficient-induction-of-inner-ear-hair-cell-like-cells-from-mouse-es-cells-using-combination-of-math1-transfection-and-conditioned-medium-from-st2-stromal-cells
#8
Yukiteru Ouji, Masaharu Sakagami, Hiroko Omori, Shinji Higashiyama, Norikazu Kawai, Tadashi Kitahara, Akio Wanaka, Masahide Yoshikawa
We sought to establish a more efficient technique for induction of inner ear hair cell-like cells (HC-like cells) from embryonic stem cells (ES cells) by using a combination of two previously reported methods; ST2 stromal cell-conditioned medium, known to be favorable for HC-like cell induction (HIST2 method), and ES cells with transfer of the Math1 gene (Math1-ES cells). Math1-ES cells carrying Tet-inducible Math1 were cultured for 14days with doxycycline in conditioned medium from cultures of ST2 stromal cells following formation of 4-day embryoid bodies (EBs)...
July 1, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28688549/curcumin-protects-against-acoustic-trauma-in-the-rat-cochlea
#9
Harun Soyalıç, Fikret Gevrek, Serhat Karaman
OBJECTIVES: In this study we evaluated the therapeutic utility of curcumin in a rodent model of acoustic trauma using histopathology, immunohistochemical, and distortion product otoacoustic emission (DPOAEs) measurements. METHODS: 28 Wistar albino rats were included in the study and randomly assigned to 4 treatment groups. The first group (group 1) served as the control and was exposed to acoustic trauma alone. Group 2 was the curcumin group. Group 3 was the curcumin plus acoustic trauma group...
August 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28686716/gsr-is-not-essential-for-the-maintenance-of-antioxidant-defenses-in-mouse-cochlea-possible-role-of-the-thioredoxin-system-as-a-functional-backup-for-gsr
#10
Chul Han, Mi-Jung Kim, Dalian Ding, Hyo-Jin Park, Karessa White, Logan Walker, Tongjun Gu, Masaru Tanokura, Tatsuya Yamasoba, Paul Linser, Richard Salvi, Shinichi Someya
Glutathione reductase (GSR), a key member of the glutathione antioxidant defense system, converts oxidized glutathione (GSSG) to reduced glutathione (GSH) and maintains the intracellular glutathione redox state to protect the cells from oxidative damage. Previous reports have shown that Gsr deficiency results in defects in host defense against bacterial infection, while diquat induces renal injury in Gsr hypomorphic mice. In flies, overexpression of GSR extended lifespan under hyperoxia. In the current study, we investigated the roles of GSR in cochlear antioxidant defense using Gsr homozygous knockout mice that were backcrossed onto the CBA/CaJ mouse strain, a normal-hearing strain that does not carry a specific Cdh23 mutation that causes progressive hair cell degeneration and early onset of hearing loss...
2017: PloS One
https://www.readbyqxmd.com/read/28680501/methods-of-hearing-preservation-during-cochlear-implantation
#11
REVIEW
Ahmed Khater, Mohammad Waheed El-Anwar
Introduction  Recent advances in surgical techniques and electrode design have made residual hearing preservation during cochlear implantation (CI) possible, achievable, and desirable. Objectives  The objective of this study was to review the literature regarding methods used for hearing preservation during CI surgery. Data Synthesis  We performed a search in the LILACS, MEDLINE, SciELO, PubMed databases, and Cochrane Library, using the keywords CI, hearing preservation, CI electrode design, and CI soft surgery...
July 2017: International Archives of Otorhinolaryngology
https://www.readbyqxmd.com/read/28669599/inactivation-of-stat3-signaling-impairs-hair-cell-differentiation-in%C3%A2-the%C3%A2-developing-mouse-cochlea
#12
Qianqian Chen, Yizhou Quan, Naitao Wang, Chengying Xie, Zhongzhong Ji, Hao He, Renjie Chai, Huawei Li, Shankai Yin, Y Eugene Chin, Xunbin Wei, Wei-Qiang Gao
Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3 leads to an inhibition on hair cell differentiation in mice in vivo and in vitro. By cell fate analysis, inactivation of STAT3 signaling shifts the cell division modes from asymmetric to symmetric divisions from supporting cells...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28663725/mice-lacking-the-alpha9-subunit-of-the-nicotinic-acetylcholine-receptor-exhibit-deficits-in-frequency-difference-limens-and-sound-localization
#13
Amanda Clause, Amanda M Lauer, Karl Kandler
Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28656549/kanamycin-damages-early-postnatal-but-not-adult-spiral-ganglion-neurons
#14
Kelei Gao, Dalian Ding, Hong Sun, Jerome Roth, Richard Salvi
Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life-threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants...
June 27, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28655499/continuous-exposure-to-low-frequency-noise-and-carbon-disulfide-combined-effects-on-hearing
#15
Thomas Venet, Maria Carreres-Pons, Monique Chalansonnet, Aurélie Thomas, Lise Merlen, Hervé Nunge, Elodie Bonfanti, Frédéric Cosnier, Jordi Llorens, Pierre Campo
Carbon disulfide (CS2) is used in industry; it has been shown to have neurotoxic effects, causing central and distal axonopathies.However, it is not considered cochleotoxic as it does not affect hair cells in the organ of Corti, and the only auditory effects reported in the literature were confined to the low-frequency region. No reports on the effects of combined exposure to low-frequency noise and CS2 have been published to date. This article focuses on the effects on rat hearing of combined exposure to noise with increasing concentrations of CS2 (0, 63,250, and 500ppm, 6h per day, 5 days per week, for 4 weeks)...
June 24, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28654047/neonatal-murine-cochlear-explant-technique-as-an-in-vitro-screening-tool-in-hearing-research
#16
Lukas D Landegger, Sonam Dilwali, Konstantina M Stankovic
While there have been remarkable advances in hearing research over the past few decades, there is still no cure for Sensorineural Hearing Loss (SNHL), a condition that typically involves damage to or loss of the delicate mechanosensory structures of the inner ear. Sophisticated in vitro and ex vivo assays have emerged in recent years, enabling the screening of an increasing number of potentially therapeutic compounds while minimizing resources and accelerating efforts to develop cures for SNHL. Though homogenous cultures of certain cell types continue to play an important role in current research, many scientists now rely on more complex organotypic cultures of murine inner ears, also known as cochlear explants...
June 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28648121/spontaneous-otoacoustic-emission-recordings-during-contralateral-pure-tone-activation-of-medial-olivocochlear-reflex
#17
E Bulut, L Öztürk
We hypothesized that cochlear frequency discrimination occurs through medial olivocochlear efferent (MOCE)-induced alterations in outer hair cell (OHC) electromotility, which is independent from basilar membrane traveling waves. After obtaining informed consent, volunteers with normal hearing (n = 10; mean age: 20.6 ± 1.2 years) and patients with unilateral deafness (n = 10; mean age: 30.2 ± 17.9 years) or bilateral deafness (n = 8; mean age: 30.7 ± 13.8 years) underwent a complete physical and audiological examination, and audiological tests including transient evoked otoacoustic emission and spontaneous otoacoustic emission (TEOAE and SOAE, respectively)...
June 26, 2017: Physiology International
https://www.readbyqxmd.com/read/28646272/rhesus-cochlear-and-vestibular-functions-are-preserved-after-inner-ear-injection-of-saline-volume-sufficient-for-gene-therapy-delivery
#18
Chenkai Dai, Mohamed Lehar, Daniel Q Sun, Lani Swarthout Rvt, John P Carey, Tim MacLachlan, Doug Brough, Hinrich Staecker, Alexandra M Della Santina, Timothy E Hullar, Charles C Della Santina
Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome...
June 23, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28642685/rab-interacting-molecules-2-and-3-directly-interact-with-the-pore-forming-cav1-3-ca-2-channel-subunit-and-promote-its-membrane-expression
#19
Maria M Picher, Ana-Maria Oprişoreanu, SangYong Jung, Katrin Michel, Susanne Schoch, Tobias Moser
Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca(2+) channels at the presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components of the presynaptic Ca(2+) channel complex, the key signaling element at the AZ. Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28636736/the-protective-effect-of-intratympanic-dexamethasone-on-streptomycin-ototoxicity-in-rats
#20
Aylin Gül, Engin Şengül, Beyhan Yılmaz, Fazıl Emre Özkurt, Mehmet Akdağ, Ayşenur Keleş, İsmail Topçu
The purpose of this experimental study was to investigate the protective role of intratympanically administered dexamethasone on the inner ears of rats that were exposed to streptomycin ototoxicity. Twenty-four adult Wistar albino rats were separated into 4 groups: Group 1 (only streptomycin), Group 2 (only intratympanic dexamethasone), Group 3 (streptomycin and intratympanic dexamethasone), and Group 4 (streptomycin and intratympanic saline). All rats were evaluated with distortion product otoacoustic emissions (DPOAE) tests before the start of treatment and on the day it ended...
June 2017: Ear, Nose, & Throat Journal
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