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https://www.readbyqxmd.com/read/28526685/differences-in-molecular-mechanisms-of-k-clearance-in-the-auditory-sensory-epithelium-of-birds-and-mammals
#1
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
#2
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 16, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28491023/characterization-of-the-transcriptomes-of-lgr5-hair-cell-progenitors-and-lgr5-supporting-cells-in-the-mouse-cochlea
#9
Cheng Cheng, Luo Guo, Ling Lu, Xiaochen Xu, ShaSha Zhang, Junyan Gao, Muhammad Waqas, Chengwen Zhu, Yan Chen, Xiaoli Zhang, Chuanying Xuan, Xia Gao, Mingliang Tang, Fangyi Chen, Haibo Shi, Huawei Li, Renjie Chai
Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28484373/evolution-and-development-of-the-inner-ear-efferent-system-transforming-a-motor-neuron-population-to-connect-to-the-most-unusual-motor-protein-via-ancient-nicotinic-receptors
#10
REVIEW
Bernd Fritzsch, Karen L Elliott
All craniate chordates have inner ears with hair cells that receive input from the brain by cholinergic centrifugal fibers, the so-called inner ear efferents (IEEs). Comparative data suggest that IEEs derive from facial branchial motor (FBM) neurons that project to the inner ear instead of facial muscles. Developmental data showed that IEEs develop adjacent to FBMs and segregation from IEEs might depend on few transcription factors uniquely associated with IEEs. Like other cholinergic terminals in the peripheral nervous system (PNS), efferent terminals signal on hair cells through nicotinic acetylcholine channels, likely composed out of alpha 9 and alpha 10 units (Chrna9, Chrna10)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28479241/ototoxicity-of-boric-acid-powder-in-a-rat-animal-model
#11
Murat Salihoglu, Salim Dogru, Enver Cesmeci, Halil Caliskan, Onuralp Kurt, Zafer Kuçukodaci, Atila Gungor
INTRODUCTION: Boric acid, which has antiseptic and acidic properties, is used to treat external and middle ear infections. However, we have not found any literature about the effect of boric acid powder on middle ear mucosa and inner ear. OBJECTIVE: The purpose of this study is to investigate possible ototoxic effects of boric acid powder (BAP) on cochlear outer hair cell function and histological changes in middle ear mucosa in a rat animal model. METHODS: Twenty healthy, mature Wistar albino rats were used in this study...
April 22, 2017: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/28459451/generation-of-inner-ear-organoids-containing-functional-hair-cells-from-human-pluripotent-stem-cells
#12
Karl R Koehler, Jing Nie, Emma Longworth-Mills, Xiao-Ping Liu, Jiyoon Lee, Jeffrey R Holt, Eri Hashino
The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28450830/spiral-ganglion-neuron-projection-development-to-the-hindbrain-in-mice-lacking-peripheral-and-or-central-target-differentiation
#13
Karen L Elliott, Jennifer Kersigo, Ning Pan, Israt Jahan, Bernd Fritzsch
We investigate the importance of the degree of peripheral or central target differentiation for mouse auditory afferent navigation to the organ of Corti and auditory nuclei in three different mouse models: first, a mouse in which the differentiation of hair cells, but not central auditory nuclei neurons is compromised (Atoh1-cre; Atoh1(f/f) ); second, a mouse in which hair cell defects are combined with a delayed defect in central auditory nuclei neurons (Pax2-cre; Atoh1(f/f) ), and third, a mouse in which both hair cells and central auditory nuclei are absent (Atoh1(-/-))...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28446866/the-contribution-of-immune-infiltrates-to-ototoxicity-and-cochlear-hair-cell-loss
#14
REVIEW
Megan B Wood, Jian Zuo
Cells of the immune system have been shown to infiltrate the cochlea after acoustic trauma or ototoxic drug treatment; however, the contribution of the immune system to hair cell loss in the inner ear is incompletely understood. Most studies have concentrated on the immediate innate response to hair cell damage using CD45 as a broad marker for all immune cells. More recent studies have used RNA sequencing, GeneChip arrays and quantitative PCR to analyze gene expression in the entire cochlea after auditory trauma, leading to a better understanding of the chemokines and cytokines that attract immune cells to the cochlea...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28440437/autophagy-related-protein-12-associates-with-anti-apoptotic-b-cell-lymphoma-2-to-promote-apoptosis-in-gentamicin-induced-inner-ear-hair-cell-loss
#15
Xiaofeng Ma, Yongze Liu, Waqas Muhammad, Dingding Liu, Junguo Wang, Han Zhou, Xia Gao, Xiaoyun Qian
The aim of the present study was to investigate the underlying mechanisms of autophagy in a gentamicin (GM)-induced ototoxic model, and to establish whether the blocking of autophagy significantly increases the survival of inner ear hair cells. Cochleae were carefully dissected from four day‑old C57BL/6J mice and randomly divided into three groups prior to explant culture: Control (culture medium), GM‑treated (culture medium + GM) and GM + 3-methyladenine (3-MA; culture medium + GM + 3‑MA). Transmission electron microscopy, immunofluorescence and western blotting were performed to observe the expression of the autophagy protein microtubule‑associated protein 1A/B‑light chain 3 in explant cultures treated with GM and the autophagy inhibitor 3‑MA...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28414155/recent-advances-in-cochlear-hair-cell-regeneration-a-promising-opportunity-for-the-treatment-of-age-related-hearing-loss
#16
REVIEW
Miren Revuelta, Francisco Santaolalla, Olatz Arteaga, Antonia Alvarez, Ana Sánchez-Del-Rey, Enrique Hilario
The objective of this paper is to review current information regarding the treatment of age-related hearing loss by using cochlear hair cell regeneration. Recent advances in the regeneration of the inner ear, including the usefulness of stem cells, are also presented. Based on the current literature, cochlear cell regeneration may well be possible in the short term and cochlear gene therapy may also be useful for the treatment of hearing loss associated with ageing. The present review provide further insight into the pathogenesis of Inner Ear senescence and aged-related hearing loss and facilitate the development of therapeutic strategies to repair hair cells damaged by ageing...
April 13, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28405467/anti-apoptotic-effect-of-dexamethasone-in-an-ototoxicity-model
#17
Jin Ho Lee, Se Heang Oh, Tae Ho Kim, Yoon Young Go, Jae-Jun Song
BACKGROUND: Dexamethasone (DEX) is used for the treatment of various inner ear diseases. However, the molecular mechanism of DEX on gentamicin induced hair cell damage is not known. Therefore, this study investigated the protective effect of DEX on gentamicin (GM)-induced ototoxicity and the effect of GM on the expression of apoptosis related genes. METHODS: The protective effects of DEX were measured by phalloidin staining of explant cultures of organ of Corti from postnatal day 2-3 mice with GM-induced hair cell loss...
2017: Biomaterials Research
https://www.readbyqxmd.com/read/28400833/over-expression-of-myosin7a-in-cochlear-hair-cells-of-circling-mice
#18
Yoo Yeon Kim, Hajin Nam, Harry Jung, Boyoung Kim, Jun Gyo Suh
Circling mouse (C57BL/6J-cir/cir) deleted the transmembrane inner ear (Tmie) gene is an animal model for human non-syndromic recessive deafness, DFNB6. In circling mouse, hair cells in the cochlea have degenerated and hair bundles have become irregularity as time goes on. Tmie protein carries out a function of the mechanoelectrical transduction channel in cochlear hair cells. Myosin7a (MYO7A) protein has key roles in development of the cochlear hair bundles as well as in the function of cochlear hair cells...
March 2017: Laboratory Animal Research
https://www.readbyqxmd.com/read/28393066/signaling-and-transcription-factors-during-inner-ear-development-the-generation-of-hair-cells-and-otic-neurons
#19
Héctor Gálvez, Gina Abelló, Fernando Giraldez
Integration between cell signals and bHLH transcription factors plays a prominent role during the development of hair cells of the inner ear. Hair cells are the sensory receptors of the inner ear, responsible for the mechano-transduction of sound waves into electrical signals. They derive from multipotent progenitors that reside in the otic placode. Progenitor commitment is the result of cell signaling from the surrounding tissues that result in the restricted expression of SoxB1 transcription factors, Sox2 and Sox3...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28383465/emerging-therapies-for-sensorineural-hearing-loss
#20
Matthew Gordon Crowson, Ronna Hertzano, Debara L Tucci
OBJECTIVE: To critically review and evaluate the proposed mechanisms and documented results of the therapeutics currently in active clinical drug trials for the treatment of sensorineural hearing loss. DATA SOURCES: US National Institutes of Health (NIH) Clinical Trials registry, MEDLINE/PubMed. STUDY SELECTION & DATA EXTRACTION: A review of the NIH Clinical Trials registry identified candidate hearing loss therapies, and supporting publications were acquired from MEDLINE/PubMed...
April 5, 2017: Otology & Neurotology
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