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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
#1
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...
April 11, 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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28367981/cochlear-gene-therapy-with-ancestral-aav-in-adult-mice-complete-transduction-of-inner-hair-cells-without-cochlear-dysfunction
#7
Jun Suzuki, Ken Hashimoto, Ru Xiao, Luk H Vandenberghe, M Charles Liberman
The use of viral vectors for inner ear gene therapy is receiving increased attention for treatment of genetic hearing disorders. Most animal studies to date have injected viral suspensions into neonatal ears, via the round window membrane. Achieving transduction of hair cells, or sensory neurons, throughout the cochlea has proven difficult, and no studies have been able to efficiently transduce sensory cells in adult ears while maintaining normal cochlear function. Here, we show, for the first time, successful transduction of all inner hair cells and the majority of outer hair cells in an adult cochlea via virus injection into the posterior semicircular canal...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28361311/directed-differentiation-of-mouse-embryonic-stem-cells-into-inner-ear-sensory-epithelia-in-3d-culture
#8
Jing Nie, Karl R Koehler, Eri Hashino
The inner ear sensory epithelium harbors mechanosensory hair cells responsible for detecting sound and maintaining balance. This protocol describes a three-dimensional (3D) culture system that efficiently generates inner ear sensory epithelia from aggregates of mouse embryonic stem (mES) cells. By mimicking the activations and repressions of key signaling pathways during in vivo inner ear development, mES cell aggregates are sequentially treated with recombinant proteins and small molecule inhibitors for activating or inhibiting the Bmp, TGFβ, Fgf, and Wnt signaling pathways...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28350294/mechanotransduction-current-is-essential-for-stability-of-the-transducing-stereocilia-in-mammalian-auditory-hair-cells
#9
A Catalina Vélez-Ortega, Mary J Freeman, Artur A Indzhykulian, Jonathan M Grossheim, Gregory I Frolenkov
Mechanotransducer channels at the tips of sensory stereocilia of inner ear hair cells are gated by the tension of 'tip links' interconnecting stereocilia. To ensure maximal sensitivity, tip links are tensioned at rest, resulting in a continuous influx of Ca(2+) into the cell. Here we show that this constitutive Ca(2+) influx, usually considered as potentially deleterious for hair cells, is in fact essential for stereocilia stability. In the auditory hair cells of young postnatal mice and rats, a reduction in mechanotransducer current, via pharmacological channel blockers or disruption of tip links, leads to stereocilia shape changes and shortening...
March 28, 2017: ELife
https://www.readbyqxmd.com/read/28346477/disruption-of-sorcs2-reveals-differences-in-the-regulation-of-stereociliary-bundle-formation-between-hair-cell-types-in-the-inner-ear
#10
Andrew Forge, Ruth R Taylor, Sally J Dawson, Michael Lovett, Daniel J Jagger
Behavioural anomalies suggesting an inner ear disorder were observed in a colony of transgenic mice. Affected animals were profoundly deaf. Severe hair bundle defects were identified in all outer and inner hair cells (OHC, IHC) in the cochlea and in hair cells of vestibular macular organs, but hair cells in cristae were essentially unaffected. Evidence suggested the disorder was likely due to gene disruption by a randomly inserted transgene construct. Whole-genome sequencing identified interruption of the SorCS2 (Sortilin-related VPS-10 domain containing protein) locus...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28343884/short-term-desensitization-of-fast-escape-behavior-associated-with-suppression-of-mauthner-cell-activity-in-larval-zebrafish
#11
Megumi Takahashi, Maya Inoue, Masashi Tanimoto, Tsunehiko Kohashi, Yoichi Oda
Escape is among the simplest animal behaviors employed to study the neural mechanisms underlying learning. Teleost fishes exhibit behavioral learning of fast escape initiated with a C-shaped body bend (C-start). C-starts are subdivided into short-latency (SLC) and long-latency (LLC) types in larval zebrafish. Whether these two can be separately modified, and the neural correlates of this modification, however, remains undetermined. We thus performed Ca(2+) imaging of Mauthner (M-) cells, a pair of giant hindbrain neurons constituting a core element of SLC circuit, during behavioral learning in larval zebrafish...
March 23, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28332011/delayed-otolith-development-does-not-impair-vestibular-circuit-formation-in-zebrafish
#12
Richard Roberts, Jeffrey Elsner, Martha W Bagnall
What is the role of normally patterned sensory signaling in development of vestibular circuits? For technical reasons, including the difficulty in depriving animals of vestibular inputs, this has been a challenging question to address. Here we take advantage of a vestibular-deficient zebrafish mutant, rock solo (AN66) , in order to examine whether normal sensory input is required for formation of vestibular-driven postural circuitry. We show that the rock solo (AN66) mutant is a splice site mutation in the secreted glycoprotein otogelin (otog), which we confirm through both whole genome sequencing and complementation with an otog early termination mutant...
March 22, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28292428/cell-cell-contact-area-affects-notch-signaling-and-notch-dependent-patterning
#13
Oren Shaya, Udi Binshtok, Micha Hersch, Dmitri Rivkin, Sheila Weinreb, Liat Amir-Zilberstein, Bassma Khamaisi, Olya Oppenheim, Ravi A Desai, Richard J Goodyear, Guy P Richardson, Christopher S Chen, David Sprinzak
During development, cells undergo dramatic changes in their morphology. By affecting contact geometry, these morphological changes could influence cellular communication. However, it has remained unclear whether and how signaling depends on contact geometry. This question is particularly relevant for Notch signaling, which coordinates neighboring cell fates through direct cell-cell signaling. Using micropatterning with a receptor trans-endocytosis assay, we show that signaling between pairs of cells correlates with their contact area...
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28271491/role-of-skeletal-muscle-in-ear-development
#14
REVIEW
Irena Rot, Mark Baguma-Nibasheka, Willard J Costain, Paul Hong, Robert Tafra, Snjezana Mardesic-Brakus, Natasa Mrduljas-Djujic, Mirna Saraga-Babic, Boris Kablar
The current paper is a continuation of our work described in Rot and Kablar, 2010. Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/-:Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration...
March 8, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28266911/transcription-factor-emx2-controls-stereociliary-bundle-orientation-of-sensory-hair-cells
#15
Tao Jiang, Katie Kindt, Doris K Wu
The asymmetric location of stereociliary bundle (hair bundle) on the apical surface of mechanosensory hair cells (HCs) dictates the direction in which a given HC can respond to cues such as sound, head movements, and water pressure. Notably, vestibular sensory organs of the inner ear, the maculae, exhibit a line of polarity reversal (LPR) across which, hair bundles are polarized in a mirror-image pattern. Similarly, HCs in neuromasts of the zebrafish lateral line system are generated as pairs, and two sibling HCs develop opposite hair bundle orientations...
March 7, 2017: ELife
https://www.readbyqxmd.com/read/28264554/hearing-improvement-in-a-j-mice-via-the-mouse-nerve-growth-factor
#16
Lixiang Gao, Ruli Ge, Gang Xie, Dandan Yao, Ping Li, Oumei Wang, Xiufang Ma, Fengchan Han
Objectives: To investigate the otoprotective effects of mouse nerve growth factor (mNGF) in A/J mice. Methods: The mice at postnatal day 7 (P7) were randomly separated into a mNGF treated group (mNGF group) and a distilled water (for injection) treated group (control group). The mNGF dissolved in distilled water or distilled water alone was given to the mice once every other day from P7 by intramuscular injection in the hips. The otoprotective effects of mNGF in A/J mice were observed in a time course manner...
March 8, 2017: Clinical and Experimental Otorhinolaryngology
https://www.readbyqxmd.com/read/28263708/supporting-cells-remove-and-replace-sensory-receptor-hair-cells-in-a-balance-organ-of-adult-mice
#17
Stephanie A Bucks, Brandon C Cox, Brittany A Vlosich, James P Manning, Tot B Nguyen, Jennifer S Stone
Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreER(T2)-expressing supporting cells replace type II hair cells...
March 6, 2017: ELife
https://www.readbyqxmd.com/read/28259711/allicin-protects-against-cisplatin-induced-vestibular-dysfunction-by-inhibiting-the-apoptotic-pathway
#18
Xianmin Wu, Jing Cai, Xiaofei Li, He Li, Jianfeng Li, Xiaohui Bai, Wenwen Liu, Yuechen Han, Lei Xu, Daogong Zhang, Haibo Wang, Zhaomin Fan
Cisplatin is an anticancer drug that causes the impairment of inner ear function as side effects, including hearing loss and balance dysfunction. The purpose of this study was to investigate the effects of allicin against cisplatin-induced vestibular dysfunction in mice and to make clear the mechanism underlying the protective effects of allicin on oto-vestibulotoxicity. Mice intraperitoneally injected with cisplatin exhibited vestibular dysfunction in swimming test, which agreed with impairment in vestibule...
March 1, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28254438/gene-therapy-restores-balance-and-auditory-functions-in-a-mouse-model-of-usher-syndrome
#19
Kevin Isgrig, Jack W Shteamer, Inna A Belyantseva, Meghan C Drummond, Tracy S Fitzgerald, Sarath Vijayakumar, Sherri M Jones, Andrew J Griffith, Thomas B Friedman, Lisa L Cunningham, Wade W Chien
Dizziness and hearing loss are among the most common disabilities. Many forms of hereditary balance and hearing disorders are caused by abnormal development of stereocilia, mechanosensory organelles on the apical surface of hair cells in the inner ear. The deaf whirler mouse, a model of human Usher syndrome (manifested by hearing loss, dizziness, and blindness), has a recessive mutation in the whirlin gene, which renders hair cell stereocilia short and dysfunctional. In this study, wild-type whirlin cDNA was delivered to the inner ears of neonatal whirler mice using adeno-associated virus serotype 2/8 (AAV8-whirlin) by injection into the posterior semicircular canal...
March 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28245737/hearing-disorders-in-cats
#20
George M Strain
Practical relevance: Auditory function is a sense that is central to life for cats - being important in situational awareness of potential predators, pursuit of prey, and for communication with conspecifics, humans and other species. Deafness in cats is most frequently the result of a genetic disorder, strongly associated with white fur and blue eyes, but may also result from acquired causes such as advancing age, ototoxic drugs, infection, environmental noise and physical trauma. Deafness can be sensorineural, where there is loss of cochlear hair cells, or conductive, where sound is muffled on its way to the inner ear...
March 2017: Journal of Feline Medicine and Surgery
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