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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
#1
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/28636944/transduction-of-repetitive-mechanical-stimuli-by-piezo1-and-piezo2-ion-channels
#2
Amanda H Lewis, Alisa F Cui, Malcolm F McDonald, Jörg Grandl
Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636736/the-protective-effect-of-intratympanic-dexamethasone-on-streptomycin-ototoxicity-in-rats
#3
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
https://www.readbyqxmd.com/read/28620284/electrophysiological-measurements-of-peripheral-vestibular-function-a-review-of-electrovestibulography
#4
REVIEW
Daniel J Brown, Christopher J Pastras, Ian S Curthoys
Electrocochleography (EcochG), incorporating the Cochlear Microphonic (CM), the Summating Potential (SP), and the cochlear Compound Action Potential (CAP), has been used to study cochlear function in humans and experimental animals since the 1930s, providing a simple objective tool to assess both hair cell (HC) and nerve sensitivity. The vestibular equivalent of ECochG, termed here Electrovestibulography (EVestG), incorporates responses of the vestibular HCs and nerve. Few research groups have utilized EVestG to study vestibular function...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28614181/cochleovestibular-gene-transfer-in-neonatal-mice-by-canalostomy
#5
Jing-Ying Guo, Yu-Ying Liu, Teng-Fei Qu, Zhe Peng, Jing Xie, Guo-Peng Wang, Shu-Sheng Gong
Impairments of the inner ear result in sensorineural hearing loss and vestibular dysfunction in humans. A large proportion of these disorders are congenital, and involve both auditory and vestibular systems. Therefore, genetic interventions to correct deficits must be administered during early developmental stages. In this study, we evaluated inner ear gene transfer in neonatal mice by canalostomy using an adeno-associated virus serotype 8 (AAV8) vector. AAV8 with the green fluorescence protein (GFP) gene was inoculated into the inner ear of the neonatal mice through the posterior semicircular canal (canalostomy)...
June 13, 2017: Neuroreport
https://www.readbyqxmd.com/read/28603488/hypothesis-of-k-recycling-defect-is-not-a-primary-deafness-mechanism-for-cx26-gjb2-deficiency
#6
REVIEW
Hong-Bo Zhao
K(+)-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, GJB2) mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. The hypothesis states that Cx26 deficiency may disrupt inner ear gap junctions and compromise sinking and recycling of expelled K(+) ions after hair cell excitation, causing accumulation of K(+)-ions in the extracellular space around hair cells producing K(+)-toxicity, which eventually induces hair cell degeneration and hearing loss...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28584970/morphometric-evaluation-of-facial-and-vestibulocochlear-nerves-using-magnetic-resonance-imaging-comparison-of-meni%C3%A3-re-s-disease-ears-with-normal-hearing-ears
#7
Annika Henneberger, Birgit Ertl-Wagner, Maximilian Reiser, Robert Gürkov, Wilhelm Flatz
Loss of neural structures (such as hair cells or neurones within the spiral ganglion) has been proposed to be involved in Menière's disease (MD) (Spoendlin et al. Acta oto-laryngologica Supplementum 499:1-21, 1; Merchant et al. Eur Arch Oto-Rhino-Laryngol Off J Eur Feder Oto-Rhino-Laryngol Soc (EUFOS) Affil German Soc Oto-Rhino-Laryngol Head Neck Surg 252(2):63-75, 2; Tsuji et al. Ann Otol Rhinol Laryngol Suppl 81:26-31, 3; Kariya, Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 28(8):1063-1068, 4; Megerian Laryngoscope 115(9):1525-1535, 5) but this has yet to be confirmed...
June 5, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28580173/sesn2-gene-ablation-enhances-susceptibility-to-gentamicin-induced-hair-cell-death-via-modulation-of-ampk-mtor-signaling
#8
Eliane Ebnoether, Alessia Ramseier, Maurizio Cortada, Daniel Bodmer, Soledad Levano-Huaman
The process of gentamicin-induced hair cell damage includes the activation of oxidative stress processes. Sestrins, as stress-responsive proteins, protect cells against oxidative stress. Sestrins, particularly Sestrin-2, suppress excessive reactive oxygen species (ROS) accumulation and inhibit mammalian target of rapamycin complex 1 (mTORC1). Thus, we addressed the role of Sestrin-2 in the regulation of sensory hair cell survival after gentamicin exposure. Here, we show that Sestrins were expressed in the inner ear tissues, and Sestrin-2 immunolocalized in sensory hair cells and spiral ganglion (SG)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28572758/activation-of-chk1-in-supporting-cells-indirectly-promotes-hair-cell-survival
#9
Azadeh Jadali, Yu-Lan M Ying, Kelvin Y Kwan
The sensory hair cells of the inner ear are exquisitely sensitive to ototoxic insults. Loss of hair cells after exposure to ototoxic agents causes hearing loss. Chemotherapeutic agents such as cisplatin causes hair cell loss. Cisplatin forms DNA mono-adducts as well as intra- and inter-strand DNA crosslinks. DNA cisplatin adducts are repaired through the DNA damage response. The decision between cell survival and cell death following DNA damage rests on factors that are involved in determining damage tolerance, cell survival and apoptosis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28555110/reduced-membrane-insertion-of-clc-k-by-v33l-barttin-results-in-loss-of-hearing-but-leaves-kidney-function-intact
#10
Hua Tan, Stefanie Bungert-Plümke, Christoph Fahlke, Gabriel Stölting
In the mammalian ear, transduction of sound stimuli is initiated by K(+) entry through mechano-sensitive channels into inner hair cells. K(+) entry is driven by a positive endocochlear potential that is maintained by the marginal cell layer of the stria vascularis. This process requires basolateral K(+) import by NKCC1 Na(+)-2Cl(-)-K(+) co-transporters as well as Cl(-) efflux through ClC-Ka/barttin or ClC-Kb/barttin channels. Multiple mutations in the gene encoding the obligatory CLC-K subunit barttin, BSND, have been identified in patients with Bartter syndrome type IV...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28549064/chemomechanical-regulation-of-myosin-ic-cross-bridges-deducing-the-elastic-properties-of-an-ensemble-from-single-molecule-mechanisms
#11
Florian Berger, A J Hudspeth
Myosin Ic is thought to be the principal constituent of the motor that adjusts mechanical responsiveness during adaptation to prolonged stimuli by hair cells, the sensory receptors of the inner ear. In this context myosin molecules operate neither as filaments, as occurs in muscles, nor as single or few molecules, as characterizes intracellular transport. Instead, myosin Ic molecules occur in a complex cluster in which they may exhibit cooperative properties. To better understand the motor's remarkable function, we introduce a theoretical description of myosin Ic's chemomechanical cycle based on experimental data from recent single-molecule studies...
May 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28532627/regenerative-medicine-in-hearing-recovery
#12
REVIEW
Edi Simoni, Giulia Orsini, Milvia Chicca, Simone Bettini, Valeria Franceschini, Alessandro Martini, Laura Astolfi
Hearing loss, or deafness, affects 360 million people worldwide of which about 32 million are children. Deafness is irreversible when it involves sensory hair cell death because the regenerative ability of these cells is lost in mammals after embryo development. The therapeutic strategies for deafness include hearing aids and/or implantable devices. However, not all patients are eligible or truly benefit from these medical devices. Regenerative medicine based on stem cell application could play a role in both improvement of extant medical devices and in vivo recovery of auditory function by regeneration of inner ear cells and neurons...
May 19, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28526685/differences-in-molecular-mechanisms-of-k-clearance-in-the-auditory-sensory-epithelium-of-birds-and-mammals
#13
Viviane Wilms, Chris Söffgen, Hans Gerd Nothwang
Mechanoelectrical transduction in the vertebrate inner ear is a highly conserved mechanism depending on K(+) influx into hair cells. Here, we investigated the molecular underpinnings of subsequent K(+) recycling in the chicken basilar papilla and compared it with those in the mammalian auditory sensory epithelium. Like mammals, the avian auditory hair cell uses KCNQ4, KCNMA1, and KCNMB1 as K(+) efflux systems. Expression of KCNQ1 and KCNE1 suggests an additional efflux apparatus in avian hair cells. Marked differences were observed for K(+) clearance...
May 19, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28526588/adam10-and-%C3%AE-secretase-regulate-sensory-regeneration-in-the-avian-vestibular-organs
#14
Mark E Warchol, Jennifer Stone, Matthew Barton, Jeffrey Ku, Rose Veile, Nicolas Daudet, Michael Lovett
The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability...
May 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28526177/two-cell-populations-participate-in-clearance-of-damaged-hair-cells-from-the-sensory-epithelia-of-the-inner-ear
#15
REVIEW
Keiko Hirose, Mark A Rutherford, Mark E Warchol
The cochlea and the vestibular organs are populated by resident macrophages, but their role in inner ear maintenance and pathology is not entirely clear. Resident macrophages in other organs are responsible for phagocytosis of injured or infected cells, and it is likely that macrophages in the inner ear serve a similar role. Hair cell injury causes macrophages to accumulate within proximity of damaged regions of the inner ear, either by exiting the vasculature and entering the labyrinth or by the resident macrophages reorganizing themselves through local movement to the areas of injury...
April 28, 2017: Hearing Research
https://www.readbyqxmd.com/read/28520533/a-fully-automated-high-throughput-zebrafish-behavioral-ototoxicity-assay
#16
Douglas W Todd, Rohit C Philip, Maki Niihori, Ryan A Ringle, Kelsey R Coyle, Sobia F Zehri, Jordan A Mudery, Ross H Francis, Jeffrey J Rodriguez, Abraham Jacob
Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells...
May 18, 2017: Zebrafish
https://www.readbyqxmd.com/read/28507101/human-myosin-viia-is-a-very-slow-processive-motor-protein-on-various-cellular-actin-structures
#17
Osamu Sato, Satoshi Komatsu, Tsuyoshi Sakai, Yoshikazu Tsukasaki, Ryosuke Tanaka, Takeomi Mizutani, Tomonobu M Watanabe, Reiko Ikebe, Mitsuo Ikebe
Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human Usher syndrome (USH) type 1B, which causes human congenital hearing and visual loss. While it has been thought that the role of human myosin VIIa is critical for USH1 protein tethering with actin and transportation along actin bundles in inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we studied the motor function of the tail-truncated human myosin VIIa dimer (HM7AΔTail/LZ) at the single-molecule level...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28503132/protecting-mammalian-hair-cells-from-aminoglycoside-toxicity-assessing-phenoxybenzamine-s-potential
#18
Paromita Majumder, Paulette A Moore, Guy P Richardson, Jonathan E Gale
Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28499298/-cochlear-implant-state-of-the-art
#19
Thomas Lenarz
Cochlear implants are the treatment of choice for the auditory rehabilitation of patients with sensory deafness. They restore the missing function of inner hair cells by transforming the acoustic signal into electrical stimuli for activation of auditory nerve fibers. Due to the very fast technology development cochlear implants provide open-set speech understanding in the majority of patients including the use of the telephone. Children can achieve a near to normal speech and language development provided their deafness is detected early after onset and implantation is performed quickly thereafter...
April 2017: Laryngo- Rhino- Otologie
https://www.readbyqxmd.com/read/28492243/identification-of-mouse-cochlear-progenitors-that-develop-hair-and-supporting-cells-in-the-organ-of-corti
#20
Jinshu Xu, Hiroo Ueno, Chelsea Y Xu, Binglai Chen, Irving L Weissman, Pin-Xian Xu
The adult mammalian cochlear sensory epithelium houses two major types of cells, mechanosensory hair cells and underlying supporting cells, and lacks regenerative capacity. Recent evidence indicates that a subset of supporting cells can spontaneously regenerate hair cells after ablation only within the first week postparturition. Here in vivo clonal analysis of mouse inner ear cells during development demonstrates clonal relationship between hair and supporting cells in sensory organs. We report the identification in mouse of a previously unknown population of multipotent stem/progenitor cells that are capable of not only contributing to the hair and supporting cells but also to other cell types, including glia, in cochlea undergoing development, maturation and repair in response to damage...
May 11, 2017: Nature Communications
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