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https://www.readbyqxmd.com/read/29770645/atoh1-regulation-in-the-cochlea-more-than-just-transcription
#1
REVIEW
Yen-Fu Cheng
More than 80% of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons, and a lack of regeneration of these cells leads to permanent hearing loss. Therefore, the regeneration of lost hair cells is an important goal for the treatment of deafness. Atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is critical in both the development and regeneration of cochlear hair cells. Atoh1 is transcriptionally regulated by several signaling pathways, including Notch and Wnt signalings...
July 13, 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29769265/reciprocal-negative-regulation-between-lmx1a-and-lmo4-is-required-for-inner-ear-formation
#2
Yanhan Huang, Jennifer Hill, Andrew Yatteau, Loksum Wong, Tao Jiang, Jelena Petrovic, Lin Gan, Lijin Dong, Doris K Wu
LIM-domain containing transcription factors (LIM-TFs) are conserved factors important for embryogenesis. The specificity of these factors in transcriptional regulation is conferred by the complexes they form with other proteins such as LIM-domain-binding (Ldb) proteins and LIM-domain only (LMO) proteins. Unlike LIM-TF, these proteins do not bind DNA directly. LMO are negative regulators of LIM-TF and they function by competing with LIM-TFs for binding to Ldbs. Although the LIM-TF Lmx1a is expressed in the developing mouse hindbrain, which provides many of the extrinsic signals for inner ear formation, conditional knockout embryos of both sexes show that the inner ear source of Lmx1a is the major contributor of ear patterning...
May 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29766830/impact-of-sphingolipid-mediators-on-determination-of-cochlear-survival-in-ototoxicity
#3
Keiji Tabuchi, Akira Hara
BACKGROUND AND OBJECTIVE: Sphingolipid metabolites, including ceramide, sphingosine, and their phosphorylates (ceramide-1-phosphonate [C1P] and sphingosine-1-phosphate [S1P]), regulate diverse cellular processes including apoptosis, the cell cycle, and cellular differentiation. Recent studies have shown that these sphingolipid metabolites are generated in response to ototoxic agents and play important roles in determining the fate of cochlear hair cells in ototoxic injury. METHODS: This review summarizes the current knowledge on the roles of sphingolipid mediators in cochlear ototoxicity...
May 15, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29760650/characterization-of-wnt-and-notch-responsive-lgr5-hair-cell-progenitors-in-the-striolar-region-of-the-neonatal-mouse-utricle
#4
Dan You, Luo Guo, Wenyan Li, Shan Sun, Yan Chen, Renjie Chai, Huawei Li
Dysfunctions in hearing and balance are largely connected with hair cell (HC) loss. Although regeneration of HCs in the adult cochlea does not occur, there is still limited capacity for HC regeneration in the mammalian utricle from a distinct population of supporting cells (SCs). In response to HC damage, these Lgr5+ SCs, especially those in the striolar region, can regenerate HCs. In this study, we isolated Lgr5+ SCs and Plp1+ SCs (which originate from the striolar and extrastriolar regions, respectively) from transgenic mice by flow cytometry so as to compare the properties of these two subsets of SCs...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29760098/cochlear-amplification-and-tuning-depend-on-the-cellular-arrangement-within-the-organ-of-corti
#5
Hamid Motallebzadeh, Joris A M Soons, Sunil Puria
The field of cochlear mechanics has been undergoing a revolution due to recent findings made possible by advancements in measurement techniques. While it has long been assumed that basilar-membrane (BM) motion is the most important determinant of sound transduction by the inner hair cells (IHCs), it turns out that other parts of the sensory epithelium closer to the IHCs, such as the reticular lamina (RL), move with significantly greater amplitude for weaker sounds. It has not been established how these findings are related to the complex cytoarchitecture of the organ of Corti between the BM and RL, which is composed of a lattice of asymmetric Y-shaped elements, each consisting of a basally slanted outer hair cell (OHC), an apically slanted phalangeal process (PhP), and a supporting Deiters' cell (DC)...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29717571/cochlear-damage-caused-by-the-striking-noise-of-titanium-head-golf-driver
#6
Yong-Ho Park, Juyong Chung, Min Young Lee, Doh Young Lee, Young Ho Kim
Objectives: To investigate how mouse cochleae are affected by the striking noise of titanium head golf driver. Methods: Thirty-two BALB/c mice (20-22 g) with normal hearing were used. The impact acoustic stimulus generated by the striking of titanium golf driver head was centered around 4.5 kHz with 120.5 dB sound pressure level. The recorded impact noise was provided to mice in two ways with the same exposure time of 288 seconds: 1,440 repetitions and an impact duration of 0...
May 3, 2018: Clinical and Experimental Otorhinolaryngology
https://www.readbyqxmd.com/read/29706463/characterizing-a-novel-vglut3-p2a-icreer-knockin-mouse-strain-in-cochlea
#7
Chao Li, Yilai Shu, Guangqin Wang, He Zhang, Ying Lu, Xiang Li, Gen Li, Lei Song, Zhiyong Liu
Precise mouse genetic studies rely on specific tools that can label specific cell types. In mouse cochlea, previous studies suggest that vesicular glutamate transporter 3 (vGlut3), also known as Slc17a8, is specifically expressed in inner hair cells (IHCs) and loss of vGlut3 causes deafness. To take advantage of its unique expression pattern, here we generate a novel vGlut3-P2A-iCreER knockin mouse strain. The P2A-iCreER cassette is precisely inserted before stop codon of vGlut3, by which the endogenous vGlut3 is intact and paired with iCreER as well...
April 17, 2018: Hearing Research
https://www.readbyqxmd.com/read/29688099/no-evidence-for-enhanced-processing-of-speech-that-is-low-pass-filtered-near-the-edge-frequency-of-cochlear-dead-regions-in-children
#8
Alicja N Malicka, Wayne J Wilson, Thomas Baer, Kevin J Munro, Richard J Baker, Deanna Miluzzi, Brian C J Moore
OBJECTIVES: Cochlear dead regions (DRs) are regions in the cochlea where the inner hair cells and/or neurons are not functioning. Adults with extensive high-frequency DRs have enhanced abilities in processing sounds with frequencies just below the edge frequency, fedge , of the DR. It was assessed whether the same is true for children. DESIGN: Performance was compared for children aged 8 to 13 years with: DRs (group DR), hearing impairment but without DRs (group NODR), and normal hearing (group NH)...
April 24, 2018: International Journal of Audiology
https://www.readbyqxmd.com/read/29687008/secondary-degeneration-of-auditory-neurons-after-topical-aminoglycoside-administration-in-a-gerbil-model
#9
Jae-Hun Lee, Min Young Lee, Phil-Sang Chung, Jae Yun Jung
Hair cells in the cochlea can be damaged by various causes. Damaged hair cells can lead to additional destruction of parts of the auditory afferent pathway sequentially, which is called secondary degeneration. Recently, researches regarding cochlear implants have been actively carried out for clinical purposes; secondary degeneration in animals is a much more practical model for identifying the prognosis of cochlear implants. However, an appropriate model for this research is not established yet. Thus, we developed a secondary degeneration model using an ototoxic drug...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29680697/regeneration-of-cochlear-hair-cells-and-hearing-recovery-through-hes1-modulation-with-sirna-nanoparticles-in-adult-guinea-pigs
#10
Xiaoping Du, Qunfeng Cai, Matthew B West, Ibrahima Youm, Xiangping Huang, Wei Li, Weihua Cheng, Don Nakmali, Donald L Ewert, Richard D Kopke
Deafness is commonly caused by the irreversible loss of mammalian cochlear hair cells (HCs) due to noise trauma, toxins, or infections. We previously demonstrated that small interfering RNAs (siRNAs) directed against the Notch pathway gene, hairy and enhancer of split 1 (Hes1), encapsulated within biocompatible poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) could regenerate HCs within ototoxin-ablated murine organotypic cultures. In the present study, we delivered this sustained-release formulation of Hes1 siRNA (siHes1) into the cochleae of noise-injured adult guinea pigs...
May 2, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29676295/effects-of-parenteral-papaverine-and-piracetam-administration-on-cochlea-following-acoustic-trauma
#11
Nurcan Yurtsever Kum, Yavuz F Yilmaz, Seren G Gurgen, Rauf O Kum, Muge Ozcan, Adnan Unal
Introduction: Noise exposure, the main cause of hearing loss in countries with lot of industries, may result both in temporary or permanent hearing loss. The goal of this study was to investigate the effects of parenteral papaverine and piracetam administration following an acoustic trauma on hearing function with histopathologic correlation. Materials and Methods: Eighteen Wistar albino rats exposed to noise for 8 h in a free environment were included. We divided the study population into three groups, and performed daily intraperitoneal injections of papaverine, piracetam, and saline, respectively, throughout the study...
March 2018: Noise & Health
https://www.readbyqxmd.com/read/29675997/hearing-vulnerability-after-noise-exposure-in-a-mouse-model-of-reactive-oxygen-species-overproduction
#12
Shigefumi Morioka, Hirofumi Sakaguchi, Taro Yamaguchi, Yuzuru Ninoyu, Hiroaki Mohri, Takashi Nakamura, Yasuo Hisa, Kiyokazu Ogita, Naoaki Saito, Takehiko Ueyama
Previous studies have convincingly argued that reactive oxygen species (ROS) contribute to the development of several major types of sensorineural hearing loss, such as noise-induced hearing loss (NIHL), drug-induced hearing loss, and age-related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic (TG) mouse line expressing the human NADPH oxidase 4 (NOX4, NOX4-TG mice), which is a constitutively active ROS-producing enzyme that does not require stimulation or an activator...
April 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29674954/bioinformatic-integration-of-molecular-networks-and-major-pathways-involved-in-mice-cochlear-and-vestibular-supporting-cells
#13
Teresa Requena, Alvaro Gallego-Martinez, Jose A Lopez-Escamez
Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29673779/protective-effect-of-gallic-acid-against-cisplatin-induced-ototoxicity-in-rats
#14
Korhan Kilic, Muhammed Sedat Sakat, Fazile Nur Ekinci Akdemir, Serkan Yildirim, Yavuz Selim Saglam, Seda Askin
INTRODUCTION: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. OBJECTIVE: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. METHODS: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each...
April 7, 2018: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/29662891/transient-abnormalities-in-masking-tuning-curve-in-early-progressive-hearing-loss-mouse-model
#15
Marion Souchal, Ludimila Labanca, Sirley Alves da Silva Carvalho, Luciana Macedo de Resende, Christelle Blavignac, Paul Avan, Fabrice Giraudet
Damage to cochlear outer hair cells (OHCs) usually affects frequency selectivity in proportion to hearing threshold increase. However, the current clinical heuristics that attributes poor hearing performance despite near-normal auditory sensitivity to auditory neuropathy or "hidden" synaptopathy overlooks possible underlying OHC impairment. Here, we document the part played by OHCs in influencing suprathreshold auditory performance in the presence of noise in a mouse model of progressive hair cell degeneration, the CD1 strain, at postnatal day 18-30 stages when high-frequency auditory thresholds remained near-normal...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29661614/a-fluorescence-based-imaging-approach-to-pharmacokinetic-analysis-of-intracochlear-drug-delivery
#16
Andrew M Ayoob, Marcello Peppi, Vishal Tandon, Robert Langer, Jeffrey T Borenstein
Advances in microelectromechanical systems (MEMS) technologies are enhancing the development of intracochlear delivery devices for the treatment of hearing loss with emerging pharmacological therapies. Direct intracochlear delivery addresses the limitations of systemic and intratympanic delivery. However, optimization of delivery parameters for these devices requires pharmacokinetic assessment of the spatiotemporal drug distribution inside the cochlea. Robust methods of measuring drug concentration in the perilymph have been developed, but lack spatial resolution along the tonotopic axis or require complex physiological measurements...
April 5, 2018: Hearing Research
https://www.readbyqxmd.com/read/29649050/temporal-bone-histopathology-in-cockayne-syndrome
#17
Ophir Handzel, Joseph B Nadol
: Cockayne syndrome (CS) is a rare autosomal recessive syndrome resulting in defective DNA repair. Its features include cachectic dwarfism, hearing loss, skin hypersensitivity to sunlight, premature aging, and dementia. Presented is a right temporal bone of a patient who died at the age of 29 years. The clinical course was compatible with type 1 CS, the classical form. Homozygous missense variant in the ERCC6 gene (Excision Repair Cross-Complementation group 6) was found, compatible with CS complementation group B...
April 11, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29620237/a-novel-missense-mutation-in-the-actg1-gene-in-a-family-with-congenital-autosomal-dominant-deafness-a-case-report
#18
Cha Gon Lee, Jahyeon Jang, Hyun-Seok Jin
The ACTG1 gene encodes the cytoskeletal protein γ-actin, which functions in non‑muscle cells and is abundant in the auditory hair cells of the cochlea. Autosomal dominant missense mutations in ACTG1 are associated with DFNA20/26, a disorder that is typically characterized by post‑lingual progressive hearing loss. To date, 17 missense mutations in ACTG1 have been reported in 20 families with DFNA20/26. The present study described a small family with autosomal dominant nonsyndromic hearing loss. A novel heterozygous missense mutation, c...
March 29, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619376/susceptibility-of-diabetic-mice-to-noise-trauma
#19
Wook Kyoung Han, Eung Hyub Kim, Sun-Ae Shin, Dong-Sik Shin, Bong Jik Kim, Ah-Ra Lyu, Yong-Ho Park
Diabetes can lead to many end-organ complications. However, the association between diabetes and hearing loss is not well understood. Here, we investigated the effect of noise exposure on diabetic mice compared with wild-type mice. Hearing threshold shifts, histopathologic changes in the cochlea, and inflammatory responses were evaluated over time. After noise exposure, more severe hearing threshold shifts, auditory hair cell loss, and synaptopathies were notable in diabetic mice compared with wild-type mice...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29605168/no-effect-of-prolonged-pulsed-high-frequency-ultrasound-imaging-of-the-basilar-membrane-on-cochlear-function-or-hair-cell-survival-found-in-an-initial-study
#20
Thomas G Landry, Manohar L Bance, Robert B Adamson, Jeremy A Brown
Miniature high frequency ultrasound devices show promise as tools for clinical middle ear and basal cochlea imaging and vibrometry. However, before clinical use it is important to verify that the ultrasound exposure does not damage the cochlea. In this initial study, electrophysiological responses of the cochlea were measured for a range of stimulus frequencies in both ears of anesthetized chinchillas, before and after exposing the organ of Corti region of one ear to pulsed focused ultrasound for 30 min. Measurements were again taken after an 11 day survival period...
December 16, 2017: Hearing Research
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