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https://www.readbyqxmd.com/read/28220769/a-connexin30-mutation-rescues-hearing-and-reveals-roles-for-gap-junctions-in-cochlear-amplification-and-micromechanics
#1
Victoria A Lukashkina, Snezana Levic, Andrei N Lukashkin, Nicola Strenzke, Ian J Russell
Accelerated age-related hearing loss disrupts high-frequency hearing in inbred CD-1 mice. The p.Ala88Val (A88V) mutation in the gene coding for the gap-junction protein connexin30 (Cx30) protects the cochlear basal turn of adult CD-1Cx30(A88V/A88V) mice from degeneration and rescues hearing. Here we report that the passive compliance of the cochlear partition and active frequency tuning of the basilar membrane are enhanced in the cochleae of CD-1Cx30(A88V/A88V) compared to CBA/J mice with sensitive high-frequency hearing, suggesting that gap junctions contribute to passive cochlear mechanics and energy distribution in the active cochlea...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28216123/ablation-of-the-auditory-cortex-results-in-changes-in-the-expression-of-neurotransmission-related-mrnas-in-the-cochlea
#2
Verónica Lamas, José M Juiz, Miguel A Merchán
The auditory cortex (AC) dynamically regulates responses of the Organ of Corti to sound through descending connections to both the medial (MOC) and lateral (LOC) olivocochlear efferent systems. We have recently provided evidence that AC has a reinforcement role in the responses to sound of the auditory brainstem nuclei. In a molecular level, we have shown that descending inputs from AC are needed to regulate the expression of molecules involved in outer hair cell (OHC) electromotility control, such as prestin and the α10 nicotinic acetylcholine receptor (nAchR)...
February 16, 2017: Hearing Research
https://www.readbyqxmd.com/read/28211069/mglur1-enhances-efferent-inhibition-of-inner-hair-cells-in-the-developing-rat-cochlea
#3
Zhanlei Ye, Juan D Goutman, Sonja J Pyott, Elisabeth Glowatzki
Just before the onset of hearing, the inner hair cells (IHCs) receive inhibitory efferent input from cholinergic medial olivocochlear (MOC) neurons originating in the brainstem. This input may serve a role in the maturation of the ascending (afferent) auditory system by inhibiting spontaneous activity of the IHCs. To investigate the molecular mechanisms regulating these IHC efferent synapses, we combined electrical stimulation of the efferent fibres with patch clamp recordings from the IHCs to measure efferent synaptic strength...
February 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28196606/imaging-and-cell-count-in-cleared-intact-cochlea-in-the-mongolian-gerbil-using-laser-scanning-confocal-microscopy
#4
M Risoud, J Sircoglou, G Dedieu, M Tardivel, C Vincent, N-X Bonne
OBJECTIVES: To draw up a clearing protocol for Mongolian gerbil cochlea, and to assess the feasibility of quantifying and analyzing 3D cell architecture in the transparent cochleae. MATERIALS AND METHODS: Freshly dissected inner ears were prepared on a 13-day protocol: fixation, microdissection, post-fixation, decalcification, pretreatment (signal enhancement, permeabilization and blocking), fluorescent labeling (indirect immunolabeling and direct labeling), dehydration, clearing in Spalteholz solution (MSBB: methyl salicylate and benzyl benzoate) and mounting...
February 9, 2017: European Annals of Otorhinolaryngology, Head and Neck Diseases
https://www.readbyqxmd.com/read/28184337/atoh1-as-a-coordinator-of-sensory-hair-cell-development-and-regeneration-in-the-cochlea
#5
Sungsu Lee, Han-Seong Jeong, Hyong-Ho Cho
Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs...
January 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28181545/gfi1-cre-mice-have-early-onset-progressive-hearing-loss-and-induce-recombination-in-numerous-inner-ear-non-hair-cells
#6
Maggie Matern, Sarath Vijayakumar, Zachary Margulies, Beatrice Milon, Yang Song, Ran Elkon, Xiaoyu Zhang, Sherri M Jones, Ronna Hertzano
Studies of developmental and functional biology largely rely on conditional expression of genes in a cell type-specific manner. Therefore, the importance of specificity and lack of inherent phenotypes for Cre-driver animals cannot be overemphasized. The Gfi1(Cre) mouse is commonly used for conditional hair cell-specific gene deletion/reporter gene activation in the inner ear. Here, using immunofluorescence and flow cytometry, we show that the Gfi1(Cre) mice produce a pattern of recombination that is not strictly limited to hair cells within the inner ear...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165504/implementation-of-a-method-to-visualize-noise-induced-hearing-loss-in-mass-stranded-cetaceans
#7
Maria Morell, Andrew Brownlow, Barry McGovern, Stephen A Raverty, Robert E Shadwick, Michel André
Assessment of the impact of noise over-exposure in stranded cetaceans is challenging, as the lesions that lead to hearing loss occur at the cellular level and inner ear cells are very sensitive to autolysis. Distinguishing ante-mortem pathology from post-mortem change has been a major constraint in diagnosing potential impact. Here, we outline a methodology applicable to the detection of noise-induced hearing loss in stranded cetaceans. Inner ears from two mass strandings of long-finned pilot whales in Scotland were processed for scanning electron microscopy observation...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165475/a-synthetic-aav-vector-enables-safe-and-efficient-gene-transfer-to-the-mammalian-inner-ear
#8
Lukas D Landegger, Bifeng Pan, Charles Askew, Sarah J Wassmer, Sarah D Gluck, Alice Galvin, Ruth Taylor, Andrew Forge, Konstantina M Stankovic, Jeffrey R Holt, Luk H Vandenberghe
Efforts to develop gene therapies for hearing loss have been hampered by the lack of safe, efficient, and clinically relevant delivery modalities. Here we demonstrate the safety and efficiency of Anc80L65, a rationally designed synthetic vector, for transgene delivery to the mouse cochlea. Ex vivo transduction of mouse organotypic explants identified Anc80L65 from a set of other adeno-associated virus (AAV) vectors as a potent vector for the cochlear cell targets. Round window membrane injection resulted in highly efficient transduction of inner and outer hair cells in mice, a substantial improvement over conventional AAV vectors...
February 6, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28163078/manganese-superoxide-dismutase-influences-the-extent-of-noise-induced-hearing-loss-in-mice
#9
Ayinuer Tuerdi, Makoto Kinoshita, Teru Kamogashira, Chisato Fujimoto, Shinnichi Iwasaki, Takahiko Shimizu, Tatsuya Yamasoba
Reactive oxygen species (ROS) generation is one of the mechanisms underlying noise-induced hearing loss (NIHL). Manganese superoxide dismutase (Mn-SOD), an antioxidant enzyme acting within the mitochondria, converts toxic superoxide to hydrogen peroxide. We investigated the role of Mn-SOD in NIHL by examining the extent of hearing loss and hair cell damage after noise exposure in C57BL/6 wild-type (WT) mice and Mn-SOD heterozygous knockout (HET) mice (n=6 each). Both HET and WT mice were exposed to 120dB sound pressure level at 4kHz octave band noise for 4h...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28154149/the-coupling-between-ca2-channels-and-the-exocytotic-ca2-sensor-at-hair-cell-ribbon-synapses-varies-tonotopically-along-the-mature-cochlea
#10
Stuart L Johnson, Jennifer Olt, Soyoun Cho, Henrique von Gersdorff, Walter Marcotti
: The cochlea processes auditory signals over a wide range of frequencies and intensities. However, the transfer characteristics at hair cell ribbon synapses are still poorly understood at different frequency locations along the cochlea. Using recordings from mature gerbils, we report here a surprisingly strong block of exocytosis by the slow Ca(2+) buffer EGTA (10 mM) in basal hair cells tuned to high frequencies (∼30 kHz). In addition, using recordings from gerbil, mouse and bullfrog auditory organs, we find that the spatial coupling between Ca(2+) influx and exocytosis changes from nanodomain in low-frequency tuned hair cells (<∼2 kHz) to progressively more microdomain in high-frequency cells (>∼2 kHz)...
February 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28145795/supernumerary-human-hair-cells-signs-of-regeneration-or-impaired-development-a-field-emission-scanning-electron-microscopy-study
#11
Helge Rask-Andersen, Hao Li, Hubert Löwenheim, Marcus Müller, Kristian Pfaller, Annelies Schrott-Fischer, Rudolf Glueckert
BACKGROUND: Current attempts to regenerate cochlear sensorineural structures motivate further inspection of the human organ of hearing. Here, we analyzed the supernumerary inner hair cell (sIHC), a possible sign of regeneration and cell replacement. METHODS: Human cochleae were studied using field emission scanning electron microscopy (FESEM; maximum resolution 2 nm) obtained from individuals aged 44, 48, and 58 years with normal sensorineural pure-tone average (PTA) thresholds (PTA <20 dB)...
February 1, 2017: Upsala Journal of Medical Sciences
https://www.readbyqxmd.com/read/28133939/reduced-acoustic-startle-response-and-peripheral-hearing-loss-in-the-5xfad-mouse-model-of-alzheimer-s-disease
#12
Timothy P O'Leary, Sooyoun Shin, Emre Fertan, Rachel N Dingle, Awad Almuklass, Rhian K Gunn, Zhiping Yu, Jian Wang, Richard E Brown
Hearing dysfunction has been associated with Alzheimer's disease in humans, but there is little data on the auditory function of mouse models of Alzheimer's disease. Furthermore, characterization of hearing ability in mouse models is needed to ensure that tests of cognition that use auditory stimuli are not confounded by hearing dysfunction. Therefore we assessed acoustic startle response and pre-pulse inhibition in the double transgenic 5xFAD mouse model of Alzheimer's disease from 3-4 to 16 months of age...
January 29, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28125514/age-related-change-in-vestibular-ganglion-cell-populations-in-individuals-with-presbycusis-and-normal-hearing
#13
Michael B Gluth, Erik G Nelson
HYPOTHESIS: We sought to establish that the decline of vestibular ganglion cell counts uniquely correlates with spiral ganglion cell counts, cochlear hair cell counts, and hearing phenotype in individuals with presbycusis. BACKGROUND: The relationship between aging in the vestibular system and aging in the cochlea is a topic of ongoing investigation. Histopathologic age-related changes the vestibular system may mirror what is seen in the cochlea, but correlations with hearing phenotype and the impact of presbycusis are not well understood...
January 25, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28118374/dynamic-expression-of-sox2-gata3-and-prox1-during-primary-auditory-neuron-development-in-the-mammalian-cochlea
#14
Koji Nishimura, Teppei Noda, Alain Dabdoub
Primary auditory neurons (PANs) connect cochlear sensory hair cells in the mammalian inner ear to cochlear nucleus neurons in the brainstem. PANs develop from neuroblasts delaminated from the proneurosensory domain of the otocyst and keep maturing until the onset of hearing after birth. There are two types of PANs: type I, which innervate the inner hair cells (IHCs), and type II, which innervate the outer hair cells (OHCs). Glial cells surrounding these neurons originate from neural crest cells and migrate to the spiral ganglion...
2017: PloS One
https://www.readbyqxmd.com/read/28115485/ick-ciliary-kinase-is-essential-for-planar-cell-polarity-formation-in-inner-ear-hair-cells-and-hearing-function
#15
Shio Okamoto, Taro Chaya, Yoshihiro Omori, Ryusuke Kuwahara, Shun Kubo, Hirofumi Sakaguchi, Takahisa Furukawa
: Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells, which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each hair cell, exhibit a typical form of PCP. While connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28112219/c-myb-knockdown-increases-the-neomycin-induced-damage-to-hair-cell-like-hei-oc1-cells-in-vitro
#16
Xiaoyu Yu, Wenwen Liu, Zhaomin Fan, Fuping Qian, Daogong Zhang, Yuechen Han, Lei Xu, Gaoying Sun, Jieyu Qi, Shasha Zhang, Mingliang Tang, Jianfeng Li, Renjie Chai, Haibo Wang
c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28102558/concise-reviews-regeneration-in-mammalian-cochlea-hair-cells-help-from-supporting-cells-transdifferentiation
#17
Bénédicte Franco, Brigitte Malgrange
It is commonly assumed that mammalian cochlear cells do not regenerate. Therefore, if hair cells are lost following an injury, no recovery could occur. However, during the first postnatal week, mice harbor some progenitor cells that retain the ability to give rise to new hair cells. These progenitor cells are in fact supporting cells. Upon hair cells loss, those cells are able to generate new hair cells both by direct transdifferentiation or following cell cycle re-entry and differentiation. However, this property of supporting cells is progressively lost after birth...
January 19, 2017: Stem Cells
https://www.readbyqxmd.com/read/28093932/involvement-of-p53-and-bcl-2-in-sensory-cell-degeneration-in-aging-rat-cochleae
#18
Yang Xu, Wei Ping Yang, Bo Hua Hu, Shiming Yang, Donald Henderson
CONCLUSION: p53 and Bcl-2 (B-cell lymphoma 2) are involved in the process of sensory cell degeneration in aging cochleae. OBJECTIVE: To determine molecular players in age-related hair cell degeneration, this study examined the changes in p53 and Bcl-2 expression at different stages of apoptotic and necrotic death of hair cells in aging rat cochleae. METHODS: Young (3-4 months) and aging (23-24 months) Fisher 344/NHsd rats were used. The thresholds of the auditory brainstem response (ABR) were measured to determine the auditory function...
January 17, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28077706/connexin-mediated-signaling-in-nonsensory-cells-is-crucial-for-the-development-of-sensory-inner-hair-cells-in-the-mouse-cochlea
#19
Stuart L Johnson, Federico Ceriani, Oliver Houston, Roman Polishchuk, Elena Polishchuk, Giulia Crispino, Veronica Zorzi, Fabio Mammano, Walter Marcotti
: Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and connexin 30 (Cx30) have been linked to syndromic and nonsyndromic hearing loss in mice and humans. The release of ATP from connexin hemichannels in cochlear nonsensory cells has been proposed to be the main trigger for action potential activity in immature sensory inner hair cells (IHCs), which is crucial for the refinement of the developing auditory circuitry. Using connexin knock-out mice, we show that IHCs fire spontaneous action potentials even in the absence of ATP-dependent intercellular Ca(2+) signaling in the nonsensory cells...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28068659/hearing-loss-after-round-window-surgery-in-mice-is-due-to-middle-ear-effusion
#20
Bovey Z Zhu, Jasmine Saleh, Kevin T Isgrig, Lisa L Cunningham, Wade W Chien
BACKGROUND: Delivery of therapeutic agents directly through the round window (RW) offers promise for treating sensorineural hearing loss. However, hearing loss can result from the surgical approach itself, and the reasons for this are poorly understood. We examined the hearing loss following the 3 major steps involved with the RW approach to access the mouse cochlea: bullostomy, RW puncture, and RW injection. METHODS: Twenty-one adult CBA/J mice underwent bullostomy alone, 10 underwent RW puncture, and 8 underwent RW injection with PBS with 5% glycerol...
January 10, 2017: Audiology & Neuro-otology
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