Author: Melissa M. McGovern Publisher: ISBN: Category : Cell differentiation Languages : en Pages : 328
Book Description
One of the most common disabilities in the US, hearing loss, is reported by The National Institutes of Health to affect approximately 36 million Americans. One of the major contributing factors to this loss in hearing is the loss of the sensory hair cells (HCs) within the cochlea. Also in the mammalian cochlea, six major groups of supporting cell (SC) subtypes reside in close proximity to HCs and may have the potential to regenerate HCs after damage. These subtypes include cells of the greater epithelial ridge, inner phalangeal/border cells, inner and outer pillar cells, Deiters' cells, Hensen cells, and Claudius cells. During embryonic development, progenitor cells differentiate into HCs or one of the SC subtypes by Notch-mediated lateral inhibition. In the neonatal mouse cochlea, many studies have shown that inhibition of Notch signaling allows SCs to convert into HCs in both normal undamaged cochleae, as well as in drug-damaged cochlear explants. This mechanism is also implicated during spontaneous HC regeneration that occurs in non-mammalian vertebrates. We and others have recently observed that spontaneous HC regeneration can also occur in the neonatal mouse cochlea. However, little is known about the molecular mechanism or the SC subtypes which act as the source of regenerated HCs. In the neonatal mouse cochlea, HCs were killed in vivo at birth using a genetically-modified mouse model to express a toxin in HCs. Subsequently, SCs formed new HCs by either direct transdifferentiation, where no cell division occurred, or by mitotic regeneration. My dissertation investigated the role of Notch signaling in the ability of SC subtypes to regenerate HCs after damage. My central hypothesis is that after HC ablation is induced at birth, Notch signaling is partially eliminated and therefore lateral inhibition is lost in neonatal SCs in a subtype specific manner, which allows some SCs, but not others, to differentiate into and regenerate HCs. Aim 1 focused on changes in the Notch signaling pathway in response to HC damage during the window of spontaneous HC regeneration. Changes in the expression of genes in the Notch pathway were measured using real time qPCR, immunostaining, and in situ hybridization. The Notch effector HeyL was increased in the apical one-third of the cochlea while other Notch players are decreased. The most notable example is the Notch effector Hes5, which is directly responsible for inhibiting HC fate, and was reduced in outer pillar cells and Deiters' cells, but not in other SC subtypes. From this we conclude that Notch signaling is reduced differentially among SC subtypes. In Aim 2 we investigated whether inhibition of Notch signaling is required for spontaneous HC regeneration to occur by maintaining active Notch signaling in all SCs in the context of HC damage. We hypothesized that maintaining active Notch signaling after HC damage will prevent SC-to-HC conversion thus preventing HC regeneration. We found significantly fewer regenerated HCs while maintaining Notch expression compared to controls with HC damage and no manipulation of Notch signaling. Therefore we conclude loss of Notch mediated lateral inhibition is required for the majority of spontaneous HC regeneration. In Aim 3 we investigated the ability of different SC subtypes to regenerate HCs by fate-mapping SC subtypes during the HC regeneration process. Since fate-mapping creates a permanent label in targeted cells, we can track their potential change in cell fate or reentry in the cell cycle after HC damage. We hypothesized that pillar cells and Deiters' cells are the source for spontaneously regenerated HC within the neonatal mouse cochlea based on our results from Aim 1. We used three CreER mouse lines to fate-map distinct groups of SC subtypes during the HC damage and regeneration process. More pillar and Deiters' cells regenerated HCs after damage than other SC populations. We found that outer pillar cells and Deiters' cells are capable of downregulating the cell cycle inhibitor, p27Kip1, after HC damage. Therefore we investigated the ability of SC subtypes to mitotically regenerate HCs by including a mitotic tracer along with fate-mapping. A larger proportion of mitotically regenerated HCs came from pillar and Deiters' cells. From these experiments, we conclude that outer pillar and Deiters' cells are the source for the majority of spontaneously regenerated HCs in vivo. This knowledge will allow targeted investigation into outer pillar cells and Deiters' cells that maintain regenerative plasticity at postnatal ages. Understanding how these cells change with age will inform efforts to induce HC regeneration in more mature cochleae. Additionally, understanding how Notch signaling regulates this regenerative plasticity will lead to the development of potential targets for the treatment of hearing loss.
Author: Huawei Li Publisher: Springer ISBN: 9811361231 Category : Medical Languages : en Pages : 180
Book Description
This book systematically discusses the pathogenesis, prevention, and the current and potential clinical treatment of hearing loss, as well as the latest advances in hearing research. Hearing loss is a prevalent sensory disorder, which according to a 2015 World Health Organization (WHO) report affected 9% of the global population in 2015. As populations continue to age, more and more people are suffering from the condition, with 60% of those aged between 65 and 75 affected. Hearing loss seriously affects patients’ ability to work ability and quality of life, and as such deafness has become an increasingly urgent social problem around the globe. Sensorineural hearing loss is mainly caused by damage to the hair cells (HCs), and the subsequent loss of spiral ganglion neurons (SGNs). Damage to the HCs in the inner ear can result from exposure to loud noises and environmental and chemical toxins as well as genetic disorders, aging, and certain medications. This book provides ENT specialists and researchers, as well as individuals affected a comprehensive introduction to the field of hearing loss.
Author: Robert J. Dooling Publisher: Springer Science & Business Media ISBN: 1461211824 Category : Science Languages : en Pages : 391
Book Description
Birds and reptiles have long fascinated investigators studying hearing and the auditory system. The highly evolved auditory inner ear of birds and reptiles shares many characteristics with the ear of mammals. Thus, the two groups are essential in understanding the form and function of the vertebrate and mammalian auditory systems. Comparative Hearing: Birds and Reptiles covers the broad range of our knowledge of hearing and acoustic communication in both groups of vertebrates. This volume addresses the many similarities in their auditory systems, as well as the known significant differences about hearing in the two groups.
Author: Sylvie Pucheu Publisher: Springer ISBN: 9783030404123 Category : Medical Languages : en Pages : 186
Book Description
Hearing loss is the most common form of sensory impairment in humans, affecting 360 million persons worldwide. In parallel, tinnitus disorder, the perception of a phantom sound often described as a ringing or buzzing, affects around 10–15% of the general population and interferes with daily life. Hyperacusis, defined as a hypersensitivity to moderate-intensity sounds often co-occurs with tinnitus suggesting a common mechanism of dysfunction for these two perceptual disorders. Whereas some drug candidates are in the process of being developed, nowadays no effective treatment exists to cure hearing loss and tinnitus. The topic of this book was selected with the goal of emphasizing mechanisms that induce hearing loss and tinnitus which lead the selection of promising targets for hearing disorder treatment. Hair cells (HC) are the sensory cells of the inner ear required for both auditory and vestibular functions in all vertebrates. HC are progressively lost during ageing and they are in addition sensitive to physical and acoustic traumas, infectious diseases and chemicals present in commonly used treatments such as anticancer, antimalarial or antibiotics. As adult mammals--including humans--cannot regenerate dead HC, all the possible injury could result in irreversible and permanent hearing loss. It has been shown, however, that a limited capacity to regenerate HC exists in mouse at an early stage of development. The regenerative capacity of HC then appears simply “repressed” in adult mammals, and one could expect it will be possible to re-activate it with an appropriate therapeutic approach which is still to be defined. Immune-mediated inner ear disease has been introduced and accepted as one SNHL pathophysiology; it responds to immunosuppressive therapy and is one of the few reversible forms of bilateral SNHL. Macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of stimuli, including noise exposure, ischemia, mitochondrial damage, and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms), in the stria vascularis. The book will include a review of inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets. The final chapter provides an overview of current animal model of tinnitus and hyperacusis. Nowadays no effective treatment exists to cure tinnitus and hyperacusis. One major obstacle to arises from the fact that tinnitus is a subjective phenomenon, the only possible diagnosis relies on self-reports of the subjects. The main constraint of the use of animal models is the subjective character of tinnitus. This chapter describe the advancement in animal models which play an important role in revealing the underlying mechanisms and treatment for tinnitus and hyperacusis.
Author: M.E. Lutman Publisher: Academic Press ISBN: 1483295168 Category : Medical Languages : en Pages : 353
Book Description
Hearing Science and Hearing Disorders focuses on the nature of the processes in the inner ear and the nervous system that mediate hearing. Organized into eight chapters, this book first discusses the nature of speech communication, the extent of hearing problems, and the pathophysiology of hearing. Four core chapters follow, in which four areas of central importance to understanding hearing disorders and their effects are covered. These areas are assessment of auditory function, the scope for technological solutions, the nature of audio-visual speech perception, and the effects of deafness upon speech production. This book will be valuable to students; to academic and professional workers concerned with hearing, speech, and their disorders; and to scientifically or medically literate people in general.
Author: Wei Xiong Publisher: Springer ISBN: 9811085579 Category : Medical Languages : en Pages : 65
Book Description
This book summarizes the emerging experimental evidence on hair-cell mechanotransduction, and covers hair’s cellular structure, biophysical properties, molecular components and functions. Auditory hair cells convert sound-induced vibration into electrical signals. This biological process, mechanotransduction, is what allows us to hear and communicate in our daily lives. However, our grasp of hair-cell mechanotransduction is still far from complete. Recent advances in molecular genetics and biophysics have helped us gain deeper insights into this process, especially the molecular constituent and operation of the channel complex. This book provides a cutting-edge snapshot for all readers who are interested in or studying how auditory hair cells detect sound.
Author: Runjan Chetty Publisher: Cambridge University Press ISBN: 1316592065 Category : Medical Languages : en Pages : 525
Book Description
Providing a unique A-Z guide to antibodies for immunohistology, this is an indispensable source for pathologists to ensure the correct application of immunohistochemistry in daily practice. Each entry includes commercial sources, clones, descriptions of stained proteins/epitopes, the full staining spectrum of normal and tumor tissues, staining pattern and cellular localization, the range of conditions of immunoreactivity, and pitfalls of the antibody's immunoprofile, giving pathologists a truly thorough quick-reference guide to sources, preparation and applications of specific antibodies. Appendices provide useful quick-reference tables of antibody panels for differential diagnoses, as well as summaries of diagnostic applications. Expanded from previous editions with over forty new entries, this handbook for diagnostic, therapeutic, prognostic and research applications of antibodies is an essential desktop book for practicing pathologists as well as researchers, residents and trainees.
Author: Yasuo Harada Publisher: Springer Science & Business Media ISBN: 9400965982 Category : Medical Languages : en Pages : 238
Book Description
The physiology of the semicircular canals was my main research interest before I began to study their morphology. In 1966, by utilizing the isolated semicircular canal of the frog, I was able to show that cell activity in the horizontal semicircular canal has the opposite polarity to that in the vertical canals, which was the first physiological proof of Ewald's law. Several transmitting electron microscope (TEM) studies had already reported on the morphology of the semicircular canal cristae; however, my morphological work was motivated by a strong desire to see whether the morphological polarity accorded to the physio logical polarity. In 1968 I happened to see the paper written by Dr David Lim, one of my close friends. His findings concerning the vestibular morphology, when examined by scanning electron microscopy (SEM), fascinated me a great deal because of the three-dimensional quality of the micro graphs. This stimulated me to become involved in vestibular morphol ogy. In the beginning, however, I faced many problems with specimen preparation for SEM, and the first few years were spent simply solving technical problems, especially those of artifacts. Many of the figures in this book have been photographed with a JEOL JSM U-3 scanning electron microscope over a decade. The sharpness of these pictures still, I think, bears comparison to the defi nition of those taken by the more sophisticated SEM scopes currently available.
Author: Andrew K. Groves Publisher: Humana ISBN: 9781071620212 Category : Medical Languages : en Pages : 398
Book Description
This volume explores the latest techniques in inner ear development, analysis of its sensory cells, and characterization and manipulation of the central auditory and vestibular pathways. The chapters in this book cover topics such as dissection and imaging of the cochlea; behavioral evaluation of animal models of diseases like tinnitus; hair cell function and regeneration; and recent advances in sequencing technology. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and comprehensive, Developmental, Physiological, and Function Neurobiology of the Inner Ear is a valuable resource for scientists and researchers interested in learning more about this developing field.
Author: Melissa M. McGovern
Author: Huawei Li
Author: Robert J. Dooling
Author: Sylvie Pucheu
Author: M.E. Lutman
Author: Wei Xiong
Author: Runjan Chetty
Author: Yasuo Harada
Author: Mary Ellen McCann
Author: Andrew K. Groves