Saccule and Utricle: Two membranous sacs within the vestibular labyrinth of the INNER EAR. The saccule communicates with COCHLEAR DUCT through the ductus reuniens, and communicates with utricle through the utriculosaccular duct from which the ENDOLYMPHATIC DUCT arises. The utricle and saccule have sensory areas (acoustic maculae) which are innervated by the VESTIBULAR NERVE.Acoustic Maculae: The sensory areas on the vertical wall of the saccule and in the floor of the utricle. The hair cells in the maculae are innervated by fibers of the VESTIBULAR NERVE.Hair Cells, Vestibular: Sensory cells in the acoustic maculae with their apical STEREOCILIA embedded in a gelatinous OTOLITHIC MEMBRANE. These hair cells are stimulated by the movement of otolithic membrane, and impulses are transmitted via the VESTIBULAR NERVE to the BRAIN STEM. Hair cells in the saccule and those in the utricle sense linear acceleration in vertical and horizontal directions, respectively.Ear, Inner: The essential part of the hearing organ consists of two labyrinthine compartments: the bony labyrinthine and the membranous labyrinth. The bony labyrinth is a complex of three interconnecting cavities or spaces (COCHLEA; VESTIBULAR LABYRINTH; and SEMICIRCULAR CANALS) in the TEMPORAL BONE. Within the bony labyrinth lies the membranous labyrinth which is a complex of sacs and tubules (COCHLEAR DUCT; SACCULE AND UTRICLE; and SEMICIRCULAR DUCTS) forming a continuous space enclosed by EPITHELIUM and connective tissue. These spaces are filled with LABYRINTHINE FLUIDS of various compositions.Otolithic Membrane: A gelatinous membrane overlying the acoustic maculae of SACCULE AND UTRICLE. It contains minute crystalline particles (otoliths) of CALCIUM CARBONATE and protein on its outer surface. In response to head movement, the otoliths shift causing distortion of the vestibular hair cells which transduce nerve signals to the BRAIN for interpretation of equilibrium.Vestibule, Labyrinth: An oval, bony chamber of the inner ear, part of the bony labyrinth. It is continuous with bony COCHLEA anteriorly, and SEMICIRCULAR CANALS posteriorly. The vestibule contains two communicating sacs (utricle and saccule) of the balancing apparatus. The oval window on its lateral wall is occupied by the base of the STAPES of the MIDDLE EAR.Vestibular Evoked Myogenic Potentials: Recorded electrical responses from muscles, especially the neck muscles or muscles around the eyes, following stimulation of the EAR VESTIBULE.Hair Cells, Auditory: Sensory cells in the organ of Corti, characterized by their apical stereocilia (hair-like projections). The inner and outer hair cells, as defined by their proximity to the core of spongy bone (the modiolus), change morphologically along the COCHLEA. Towards the cochlear apex, the length of hair cell bodies and their apical STEREOCILIA increase, allowing differential responses to various frequencies of sound.Vestibular Nerve: The vestibular part of the 8th cranial nerve (VESTIBULOCOCHLEAR NERVE). The vestibular nerve fibers arise from neurons of Scarpa's ganglion and project peripherally to vestibular hair cells and centrally to the VESTIBULAR NUCLEI of the BRAIN STEM. These fibers mediate the sense of balance and head position.PeptidoglycanRana catesbeiana: A species of the family Ranidae (true frogs). The only anuran properly referred to by the common name "bullfrog", it is the largest native anuran in North America.Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis.Stereocilia: Mechanosensing organelles of hair cells which respond to fluid motion or fluid pressure changes. They have various functions in many different animals, but are primarily used in hearing.Labyrinth Diseases: Pathological processes of the inner ear (LABYRINTH) which contains the essential apparatus of hearing (COCHLEA) and balance (SEMICIRCULAR CANALS).Cochlea: The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH.Labyrinth Supporting Cells: Cells forming a framework supporting the sensory AUDITORY HAIR CELLS in the organ of Corti. Lateral to the medial inner hair cells, there are inner pillar cells, outer pillar cells, Deiters cells, Hensens cells, Claudius cells, Boettchers cells, and others.Semicircular Canals: Three long canals (anterior, posterior, and lateral) of the bony labyrinth. They are set at right angles to each other and are situated posterosuperior to the vestibule of the bony labyrinth (VESTIBULAR LABYRINTH). The semicircular canals have five openings into the vestibule with one shared by the anterior and the posterior canals. Within the canals are the SEMICIRCULAR DUCTS.Endolymph: The lymph fluid found in the membranous labyrinth of the ear. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Hemospermia: Blood in the SEMEN, usually due to INFLAMMATION of the PROSTATE, the SEMINAL VESICLES, or both.Thiamine Pyrophosphatase: An enzyme that hydrolyzes thiamine pyrophosphate to thiamine monophosphate plus inorganic phosphate. EC 3.6.1.-.Transcription Factor Brn-3C: A POU domain factor that activates neuronal cell GENETIC TRANSCRIPTION of GENES encoding NEUROFILAMENT PROTEINS, alpha internexin, and SYNAPTOSOMAL-ASSOCIATED PROTEIN 25. Mutations in the Brn-3c gene have been associated with DEAFNESS.Batrachoidiformes: An order of bottom fishes with short, small, spinous dorsal fins. It is comprised of one family (Batrachoididae) and about 70 species.Hair Cells, Auditory, Inner: Auditory sensory cells of organ of Corti, usually placed in one row medially to the core of spongy bone (the modiolus). Inner hair cells are in fewer numbers than the OUTER AUDITORY HAIR CELLS, and their STEREOCILIA are approximately twice as thick as those of the outer hair cells.Goldfish: Common name for Carassius auratus, a type of carp (CARPS).Temporal Bone: Either of a pair of compound bones forming the lateral (left and right) surfaces and base of the skull which contains the organs of hearing. It is a large bone formed by the fusion of parts: the squamous (the flattened anterior-superior part), the tympanic (the curved anterior-inferior part), the mastoid (the irregular posterior portion), and the petrous (the part at the base of the skull).Microscopy, Electron, Scanning: Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY.Diaminopimelic AcidOrgan Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Hearing: The ability or act of sensing and transducing ACOUSTIC STIMULATION to the CENTRAL NERVOUS SYSTEM. It is also called audition.TurtlesRegeneration: The physiological renewal, repair, or replacement of tissue.Pimelic Acids: A group of compounds that are derivatives of heptanedioic acid with the general formula R-C7H11O4.Mice, Inbred CBAMicroscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Cell Wall: The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Nootropic Agents: Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms. While no potent nootropic drugs have yet been accepted for general use, several are being actively investigated.Meniere Disease: A disease of the inner ear (LABYRINTH) that is characterized by fluctuating SENSORINEURAL HEARING LOSS; TINNITUS; episodic VERTIGO; and aural fullness. It is the most common form of endolymphatic hydrops.Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (COCHLEAR NERVE) which is concerned with hearing and a vestibular part (VESTIBULAR NERVE) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the SPIRAL GANGLION and project to the cochlear nuclei (COCHLEAR NUCLEUS). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the VESTIBULAR NUCLEI.Epithelium: One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.APUD Cells: Cells with the capacity to take up and decarboxylate the amine precursors DIHYDROXYPHENYLALANINE or 5-HYDROXYTRYPTOPHAN. This is a property of endocrine cells of neural and non-neural origin. APUDOMA is a general term collectively applied to tumors associated with APUD cells.Dissection: The separation and isolation of tissues for surgical purposes, or for the analysis or study of their structures.Cyprinidae: A family of freshwater fish comprising the minnows or CARPS.Neurons, Efferent: Neurons which send impulses peripherally to activate muscles or secretory cells.Hearing Loss, Noise-Induced: Hearing loss due to exposure to explosive loud noise or chronic exposure to sound level greater than 85 dB. The hearing loss is often in the frequency range 4000-6000 hertz.Anura: An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae.Histocytochemistry: Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.Evoked Potentials, Auditory: The electric response evoked in the CEREBRAL CORTEX by ACOUSTIC STIMULATION or stimulation of the AUDITORY PATHWAYS.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Gentamicins: A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Acoustic Stimulation: Use of sound to elicit a response in the nervous system.Vestibular Diseases: Pathological processes of the VESTIBULAR LABYRINTH which contains part of the balancing apparatus. Patients with vestibular diseases show instability and are at risk of frequent falls.Chemical Precipitation: The formation of a solid in a solution as a result of a chemical reaction or the aggregation of soluble substances into complexes large enough to fall out of solution.Lanthanum: Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Auditory Threshold: The audibility limit of discriminating sound intensity and pitch.Animals, Newborn: Refers to animals in the period of time just after birth.Retinal Pigments: Photosensitive protein complexes of varied light absorption properties which are expressed in the PHOTORECEPTOR CELLS. They are OPSINS conjugated with VITAMIN A-based chromophores. Chromophores capture photons of light, leading to the activation of opsins and a biochemical cascade that ultimately excites the photoreceptor cells.Noise: Any sound which is unwanted or interferes with HEARING other sounds.Sulfates: Inorganic salts of sulfuric acid.Photoreceptor Cells: Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.Auditory Pathways: NEURAL PATHWAYS and connections within the CENTRAL NERVOUS SYSTEM, beginning at the hair cells of the ORGAN OF CORTI, continuing along the eighth cranial nerve, and terminating at the AUDITORY CORTEX.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 126.96.36.199.Osmotic Pressure: The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.TritiumStaining and Labeling: The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts.
SacculeUtricle (ear)Otolith: An otolith (οτο-, oto-, ear + λιθος, lithos, a stone), also called statoconium or otoconium, is a structure in the saccule or utricle of the inner ear, specifically in the vestibular labyrinth of vertebrates. They have been identified in both extinct and extant vertebrates.Stereocilia (inner ear): In the inner ear, stereocilia are the mechanosensing organelles of hair cells, which respond to fluid motion in numerous types of animals for various functions, including hearing and balance. They are about 10–50 micrometers in length and share some similar features of microvilli.Peptidoglycan binding domainTacrineNeomycinAutoimmune inner ear disease: Autoimmune inner ear disease is a suspected autoimmune disease characterized by rapidly progressive bilateral sensorineural hearing loss.Inner Ear, Autoimmune (eMedicine, 2006) It occurs when the body's immune system attacks cells in the inner ear that are mistaken for a virus or bacteria.Otto DeitersVestibular system: The vestibular system, in most mammals, is the sensory system that provides the leading contribution about the sense of balance and spatial orientation for the purpose of coordinating movement with balance. Together with the cochlea, a part of the auditory system, it constitutes the labyrinth of the inner ear in most mammals, situated in the vestibulum in the inner ear (Figure 1).Endolymph: Endolymph is the fluid contained in the membranous labyrinth of the inner ear. It is also called Scarpa's fluid, after Antonio Scarpa.Prostatic utricle: The prostatic utricle (Latin for "pouch of the prostate") is a small indentation in the prostatic urethra, at the apex of the urethral crest, on the seminal colliculus (verumontanum), laterally flanked by openings of the ejaculatory ducts. It is also known as the vagina masculina or (in older literature) vesicula prostatica.Thiamine pyrophosphatase: Thiamine pyrophosphatase is an enzyme which cleaves thiamine pyrophosphate.Midshipman fishEdna's Goldfish: Edna's Goldfish was an American ska punk band from Long Island, New York.Eagle syndrome: Eagle syndrome (also termed stylohyoid syndrome styloid syndrome, styloid-stylohyoid syndrome, or styloid–carotid artery syndrome) is a rare condition caused by an elongated or deviated styloid process and/or calcification of the stylohyoid ligament, which interferes with adjacent anatomical structures giving rise to pain.Field emission probesDiaminopimelic acidEquivalent rectangular bandwidth: The equivalent rectangular bandwidth or ERB is a measure used in psychoacoustics, which gives an approximation to the bandwidths of the filters in human hearing, using the unrealistic but convenient simplification of modeling the filters as rectangular band-pass filters.Turtle farming: Turtle farming is the practice of raising turtles and tortoises of various species commercially. Raised animals are sold for use as gourmet food, traditional medicine ingredients, or as pets.Regeneration (biology): In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organisms, and ecosystems resilient to natural fluctuations or events that cause disturbance or damage. Every species is capable of regeneration, from bacteria to humans.Pimelic acidLow-voltage electron microscope: Low-voltage electron microscope (LVEM) is an electron microscope which operates at accelerating voltages of a few kiloelectronvolts or less. While the low voltage electron microscopy technique will never replace conventional high voltage electron microscopes, it is quickly becoming appreciated for many different disciplines.Cell envelope: The cell envelope comprises the inner cell membrane and the cell wall of a bacterium, if present, plus a bacterial outer membrane, if one is present (i.e.CisternaColuracetam: Coluracetam (INN) (code name BCI-540; formerly MKC-231) is a nootropic agent of the racetam family. It was initially developed and tested by the Mitsubishi Tanabe Pharma Corporation for Alzheimer's disease.Vestibulocochlear dysfunction progressive familial: Vestibulocochlear dysfunction progressive familial, known also as familial progressive vestibulocochlear dysfunction is an autosomal dominant disease that results in sensorineural hearing loss and vestibular areflexia. Patients report feelings of vague dissiness, blurred vision, dysequilibrium in the dark, and progressive hearing impairment.Stratified squamous epithelium: A stratified squamous epithelium consists of squamous (flattened) epithelial cells arranged in layers upon a basal membrane. Only one layer is in contact with the basement membrane; the other layers adhere to one another to maintain structural integrity.APUD cell: [hormones.jpg|right|thumb|350px|Actions of the major digestive hormones] secreted by APUD cellsDissection puzzle: A dissection puzzle, also called a transformation puzzle or Richter Puzzle, is a tiling puzzle where a set of pieces can be assembled in different ways to produce two or more distinct geometric shapes. The creation of new dissection puzzles is also considered to be a type of dissection puzzle.Notropis: Notropis is a genus of fish in the family Cyprinidae, the carps and minnows. They are known commonly as eastern shiners.Noise-induced hearing loss: Noise-induced hearing loss (NIHL) is hearing impairment resulting from exposure to high decibel (loud) sound that may exhibit as loss of a narrow range of frequencies, impaired cognitive perception of sound or other impairment, including hyperacusis or tinnitus. Hearing may deteriorate gradually from chronic and repeated noise exposure, such as loud music or background noise, or suddenly, from an acute, high intensity noise incident including gunshots and airhorns.Hemiphractidae: The Hemiphractidae are a family of frogs from South and Central America. Previously, this group had been classified as a subfamily (Hemiphractinae) under family Hylidae.Auditory event: Auditory events describe the subjective perception, when listening to a certain sound situation. This term was introduced by Jens Blauert (Ruhr-University Bochum) in 1966, in order to distinguish clearly between the physical sound field and the auditory perception of the sound.List of strains of Escherichia coli: Escherichia coli is a well studied bacterium that was first identified by Theodor Escherich, after whom it was later named.GentamicinNeuromorphology: Neuromorphology (from Greek νεῦρον, neuron, "nerve"; μορφή, morphé, “form”; -λογία, -logia, “study of”[is the study of nervous system] form, shape, and structure. The study involves looking at a particular part of the nervous system from a [[Molecular biology|molecular and cellular level and connecting it to a physiological and anatomical point of view.Dog healthLanthanum(III) bromideNecrobiology: Necrobiology comprises the life processes associated with morphological, biochemical, and molecular changes which predispose, precede, and accompany cell death, as well as the consequences and tissue response to cell death. The word is derived from the Greek νεκρό meaning "death", βìο meaning "life", and λόγος meaning "the study of".Temporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingPhotopigment: Photopigments are unstable pigments that undergo a chemical change when they absorb light. The term is generally applied to the non-protein chromophore moiety of photosensitive chromoproteins, such as the pigments involved in photosynthesis and photoreception.List of noise topics: This is a list of noise topics.Rod cellTartrate-resistant acid phosphatase: Tartrate-resistant acid phosphatase (TRAP or TRAPase), also called acid phosphatase 5, tartrate resistant (ACP5), is a glycosylated monomeric metalloprotein enzyme expressed in mammals. It has a molecular weight of approximately 35kDa, a basic isoelectric point (7.Oncotic pressure: Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure exerted by proteins, notably albumin, in a blood vessel's plasma (blood/liquid) that usually tends to pull water into the circulatory system. It is the opposing force to capillary filtration pressure and interstitial colloidal osmotic pressure.Tritium illumination: Tritium illumination is the use of gaseous tritium, a radioactive isotope of hydrogen, to create visible light. Tritium emits electrons through beta decay, and, when they interact with a phosphor material, fluorescent light is created, a process called radioluminescence.Vital stain: A vital stain in a casual usage may mean a stain that can be applied on living cells without killing them. Vital stains have been useful for diagnostic and surgical techniques in a variety of medical specialties.
(1/238) Immunocytochemical and morphological evidence for intracellular self-repair as an important contributor to mammalian hair cell recovery.
Although recent studies have provided evidence for hair cell regeneration in mammalian inner ears, the mechanism underlying this regenerative process is still under debate. Here we report immunocytochemical, histological, electron microscopic, and autoradiographic evidence that, in cultured postnatal rat utricles, a substantial number of hair cells can survive gentamicin insult even their stereocilia are lost. These partially damaged hair cells can survive for a prolonged time and regrow the stereocilia. Although the number of stereocilia-bearing hair cells increases over time after gentamicin insult, hair cell and supporting cell numbers remain essentially unchanged. Tritiated thymidine autoradiography and bromodeoxyuridine immunocytochemistry of the cultures demonstrate that cell proliferation in the sensory epithelium is very limited and is far below the number of recovered hair cells. Furthermore, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling analysis indicates that gentamicin-induced apoptosis in the sensory epithelium occurs mainly during a 2 d treatment period, and additional cell death is minimal 2-11 d after treatment. Considered together, intracellular repair of partially damaged hair cells can be an important contributor to spontaneous hair cell recovery in mammalian inner ears. (+info)
(2/238) Functional expression of exogenous proteins in mammalian sensory hair cells infected with adenoviral vectors.
To understand the function of specific proteins in sensory hair cells, it is necessary to add or inactivate those proteins in a system where their physiological effects can be studied. Unfortunately, the usefulness of heterologous expression systems for the study of many hair cell proteins is limited by the inherent difficulty of reconstituting the hair cell's exquisite cytoarchitecture. Expression of exogenous proteins within hair cells themselves may provide an alternative approach. Because recombinant viruses were efficient vectors for gene delivery in other systems, we screened three viral vectors for their ability to express exogenous genes in hair cells of organotypic cultures from mouse auditory and vestibular organs. We observed no expression of the genes for beta-galactosidase or green fluorescent protein (GFP) with either herpes simplex virus or adeno-associated virus. On the other hand, we found robust expression of GFP in hair cells exposed to a recombinant, replication-deficient adenovirus that carried the gene for GFP driven by a cytomegalovirus promoter. Titers of 4 x 10(7) pfu/ml were sufficient for expression in 50% of the approximately 1,000 hair cells in the utricular epithelium; < 1% of the nonhair cells in the epithelium were GFP positive. Expression of GFP was evident as early as 12 h postinfection, was maximal at 4 days, and continued for at least 10 days. Over the first 36 h there was no evidence of toxicity. We recorded normal voltage-dependent and transduction currents from infected cells identified by GFP fluorescence. At longer times hair bundle integrity was compromised despite a cell body that appeared healthy. To assess the ability of adenovirus-mediated gene transfer to alter hair cell function we introduced the gene for the ion channel Kir2.1. We used an adenovirus vector encoding Kir2.1 fused to GFP under the control of an ecdysone promoter. Unlike the diffuse distribution within the cell body we observed with GFP, the ion channel-GFP fusion showed a pattern of fluorescence that was restricted to the cell membrane and a few extranuclear punctate regions. Patch-clamp recordings confirmed the expression of an inward rectifier with a conductance of 43 nS, over an order of magnitude larger than the endogenous inward rectifier. The zero-current potential in infected cells was shifted by -17 mV. These results demonstrate an efficient method for gene transfer into both vestibular and auditory hair cells in culture, which can be used to study the effects of gene products on hair cell function. (+info)
(3/238) Otx1 and Otx2 activities are required for the normal development of the mouse inner ear.
The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs. (+info)
(4/238) Morphological, morphometric, and functional differences in the vestibular organ of different breeds of the rat (Rattus norvegicus).
In the laboratory rat, differences in shape, dimension and function of the cochlea have been reported for various breeds. In contrast, no comparable investigations to date have been undertaken for the vestibular organ in different breeds of the rat. Vestibular organs of two breeds of rat (Wistar, Sprague-Dawley) were analyzed morphologically and morphometrically by means of microdissection techniques in order to determine the mechanical sensitivity of the cupula according to Oman et al; (Acta Otolaryngol., 1987;103:1-13, 1987). Differences in shape of the lateral semicircular duct exist between the two breeds and the cupular mechanical sensitivity is significantly higher in Wistar than in Sprague-Dawley rats. With respect to the other semicircular ducts, no differences in shape were found between the two strains. The cupular mechanical sensitivity of the anterior semicircular duct, however, is higher in Wistar than in Sprague-Dawley rats. The breeds also differ in the shape of their utriculus; obviously a correlation exists between the latter and the cupular mechanical sensitivity of the semicircular ducts. There are differences in the vestibular organs between the two breeds of the laboratory rat investigated. The cupular mechanical sensitivity of the semicircular duct does not seem to be correlated to body mass. The size and morphology of the utriculus influence the mechanical sensitivity of a single duct, but differences only become significant if other parameters also differ. (+info)
(5/238) Math1: an essential gene for the generation of inner ear hair cells.
The mammalian inner ear contains the cochlea and vestibular organs, which are responsible for hearing and balance, respectively. The epithelia of these sensory organs contain hair cells that function as mechanoreceptors to transduce sound and head motion. The molecular mechanisms underlying hair cell development and differentiation are poorly understood. Math1, a mouse homolog of the Drosophila proneural gene atonal, is expressed in inner ear sensory epithelia. Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells. This gene is thus required for the genesis of hair cells. (+info)
(6/238) Chemical composition of saccular endolymph and otolith in fish inner ear: lack of spatial uniformity.
Fish otoliths provide a record of age, growth, and environmental influences. In both trout and turbot, spatial chemical investigation of the endolymph surrounding the otolith (sagitta) showed a lack of uniformity. Proteins, PO(3-)(4), and Mg(2+) were significantly more concentrated in the proximal (facing the macula) than distal zone, whereas the opposite was observed for K(+) and total CO(2) (totCO(2)). Na(+) concentration ([Na(+)]) was 20% higher in the proximal zone in trout but not in turbot. Total Ca and Cl(-) contents were uniformly distributed in both species. We propose that the endolymphatic gradients of protein and totCO(2) concentration within the endolymph are involved in the otolithic biocalcification process. Microchemical analyses of otolith sections by wavelength dispersive spectrometry showed a lack of spatial uniformity in the K/Ca and Na/Ca ratios, whereas the Sr/Ca ratio was uniform. There is a clear relationship between endolymph and otolith [K(+)], but the interpretation of the results for [Na(+)] needs further investigation. Thus the lack of uniformity in the otolith composition must be taken into account when investigating otolith microchemistry. (+info)
(7/238) Peripherin immunoreactivity labels small diameter vestibular 'bouton' afferents in rodents.
Recent morphophysiological studies have described three different subpopulations of vestibular afferents. The purpose of this study was to determine whether peripherin, a 56-kDa type III intermediate filament protein present in small sensory neurons in dorsal root ganglion and spiral ganglion cells, would also label thin vestibular afferents. Peripherin immunohistochemistry was done on vestibular sensory organs (cristae ampullares, utriculi and sacculi) of chinchillas, rats, and mice. In these sensory organs, immunoreactivity was confined to the extrastriolar region of the utriculus and the peripheral region of the crista. The labelled terminals were all boutons, except for an occasional calyx. In vestibular ganglia, immunoreactivity was restricted to small vestibular ganglion cells with thin axons. The immunoreactive central axons of vestibular ganglion cells form narrow bundles as they pass through the caudal spinal trigeminal tract. As they exit this tract, several bundles coalesce to form a single, narrow bundle passing caudally through the ventral part of the lateral vestibular nucleus. Finally, we conclude that all labelled axons and terminals were vestibular afferents rather than efferents, as no immunoreactivity in the vestibular efferent nucleus of the brainstem was observed. (+info)
(8/238) Differentiation of mammalian vestibular hair cells from conditionally immortal, postnatal supporting cells.
We provide evidence from a newly established, conditionally immortal cell line (UB/UE-1) that vestibular supporting cells from the mammalian inner ear can differentiate postnatally into more than one variant of hair cell. A clonal supporting cell line was established from pure utricular sensory epithelia of H2k(b)tsA58 transgenic mice 2 d after birth. Cell proliferation was dependent on conditional expression of the immortalizing gene, the "T" antigen from the SV40 virus. Proliferating cells expressed cytokeratins, and patch-clamp recordings revealed that they all expressed small membrane currents with little time-dependence. They stopped dividing within 2 d of being transferred to differentiating conditions, and within a week they formed three defined populations expressing membrane currents characteristic of supporting cells and two kinds of neonatal hair cell. The cells expressed several characteristic features of normal hair cells, including the transcription factor Brn3.1, a functional acetylcholine receptor composed of alpha9 subunits, and the cytoskeletal proteins myosin VI, myosin VIIa, and fimbrin. Immunofluorescence labeling and electron microscopy showed that the cells formed complex cytoskeletal arrays on their upper surfaces with structural features resembling those at the apices of normal hair cells. The cell line UB/UE-1 provides a valuable in vitro preparation in which the expression of numerous structural and physiological components can be initiated or upregulated during early stages of mammalian hair cell commitment and differentiation. (+info)