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Sample records for auditory hair cells

  1. Auditory hair cell precursors immortalized from the mammalian inner ear.

    OpenAIRE

    Rivolta, M.N.; Grix, N; Lawlor, P.; Ashmore, J. F.; Jagger, D J; Holley, M C

    1998-01-01

    Mammalian auditory hair cells are few in number, experimentally inaccessible, and do not proliferate postnatally or in vitro. Immortal cell lines with the potential to differentiate into auditory hair cells would substantially facilitate auditory research, drug development, and the isolation of critical molecules involved in hair cell biology. We have established two conditionally immortal cell lines that express at least five characteristic hair cell markers. These markers are the transcript...

  2. Retinoic Acid Stimulates Regeneration of Mammalian Auditory Hair Cells

    Science.gov (United States)

    Lefebvre, Philippe P.; Malgrange, Brigitte; Staecker, Hinrich; Moonen, Gustave; van de Water, Thomas R.

    1993-04-01

    Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage.

  3. Therapeutic potential of stem cells in auditory hair cell repair

    Directory of Open Access Journals (Sweden)

    Ryuji Hata

    2009-01-01

    Full Text Available The prevalence of acquired hearing loss is very high. About 10% of the total population and more than one third of the population over 65 years suffer from debilitating hearing loss. The most common type of hearing loss in adults is idiopathic sudden sensorineural hearing loss (ISSHL. In the majority of cases, ISSHL is permanent and typically associated with loss of sensory hair cells in the organ of Corti. Following the loss of sensory hair cells, the auditory neurons undergo secondary degeneration. Sensory hair cells and auditory neurons do not regenerate throughout life, and loss of these cells is irreversible and cumulative. However, recent advances in stem cell biology have gained hope that stem cell therapy comes closer to regenerating sensory hair cells in humans. A major advance in the prospects for the use of stem cells to restore normal hearing comes with the recent discovery that hair cells can be generated ex vivo from embryonic stem (ES cells, adult inner ear stem cells and neural stem cells. Furthermore, there is increasing evidence that stem cells can promote damaged cell repair in part by secreting diffusible molecules such as growth factors. These results suggest that stem-cell-based treatment regimens can be applicable to the damaged inner ear as future clinical applications.Previously we have established an animal model of cochlear ischemia in gerbils and showed progressive hair cell loss up to 4 days after ischemia. Auditory brain stem response (ABR recordings have demonstrated that this gerbil model displays severe deafness just after cochlear ischemia and gradually recovers thereafter. These pathological findings and clinical manifestations are reminiscent of ISSHL in humans. In this study, we have shown the effectiveness of stem cell therapy by using this animal model of ISSHL.

  4. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhu Hongliang; Li Shengli; Yao Xiaobao; Wang Xiaoxia

    2006-01-01

    Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.

  5. Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization

    OpenAIRE

    Sipe, Conor W.; Liu, Lixia; Lee, Jianyi; Grimsley-Myers, Cynthia; Lu, Xiaowei

    2013-01-01

    The V-shaped hair bundles atop auditory hair cells and their uniform orientation are manifestations of epithelial planar cell polarity (PCP) required for proper perception of sound. PCP is regulated at the tissue level by a conserved core Wnt/PCP pathway. However, the hair cell-intrinsic polarity machinery is poorly understood. Recent findings implicate hair cell microtubules in planar polarization of hair cells. To elucidate the microtubule-mediated polarity pathway, we analyzed Lis1 functio...

  6. Activated Notch Causes Deafness by Promoting a Supporting Cell Phenotype in Developing Auditory Hair Cells

    OpenAIRE

    Grace Savoy-Burke; Felicia A Gilels; Wei Pan; Diana Pratt; Jianwen Que; Lin Gan; White, Patricia M.; Kiernan, Amy E.

    2014-01-01

    Purpose To determine whether activated Notch can promote a supporting cell fate during sensory cell differentiation in the inner ear. Methods An activated form of the Notch1 receptor (NICD) was expressed in early differentiating hair cells using a Gfi1-Cre mouse allele. To determine the effects of activated Notch on developing hair cells, Gfi1-NICD animals and their littermate controls were assessed at 5 weeks for hearing by measuring auditory brainstem responses (ABRs) and distortion product...

  7. Developmental segregation in the afferent projections to mammalian auditory hair cells.

    OpenAIRE

    Echteler, S M

    1992-01-01

    The mammalian ear contains two types of auditory receptors, inner and outer hair cells, that lie in close proximity to each other within the sensory epithelium of the cochlea. In adult mammals, these two classes of auditory hair cells are innervated by separate populations of afferent neurons that differ strikingly in their cellular morphology and their pattern of arborization within the cochlea. At present, it is unclear when or how these distinctive patterns of cochlear innervation emerge a...

  8. My oh my(osin): Insights into how auditory hair cells count, measure, and shape

    OpenAIRE

    Pollock, Lana M.; Chou, Shih-Wei; McDermott, Brian M., Jr.

    2016-01-01

    The mechanisms underlying mechanosensory hair bundle formation in auditory sensory cells are largely mysterious. In this issue, Lelli et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201509017) reveal that a pair of molecular motors, myosin IIIa and myosin IIIb, is involved in the hair bundle’s morphology and hearing.

  9. Auditory hair cell centrioles undergo confined Brownian motion throughout the developmental migration of the kinocilium.

    OpenAIRE

    Lepelletier, Léa; de Monvel, Jacques Boutet; Buisson, Johanna; Desdouets, Chantal; Petit, Christine

    2013-01-01

    Planar polarization of the forming hair bundle, the mechanosensory antenna of auditory hair cells, depends on the poorly characterized center-to-edge displacement of a primary cilium, the kinocilium, at their apical surface. Taking advantage of the gradient of hair cell differentiation along the cochlea, we reconstituted a map of the kinocilia displacements in the mouse embryonic cochlea. We then developed a cochlear organotypic culture and video-microscopy approach to monitor the movements o...

  10. Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms

    OpenAIRE

    Sipe, Conor W.; Lu, Xiaowei

    2011-01-01

    Auditory hair cells represent one of the most prominent examples of epithelial planar polarity. In the auditory sensory epithelium, planar polarity of individual hair cells is defined by their V-shaped hair bundle, the mechanotransduction organelle located on the apical surface. At the tissue level, all hair cells display uniform planar polarity across the epithelium. Although it is known that tissue planar polarity is controlled by non-canonical Wnt/planar cell polarity (PCP) signaling, the ...

  11. Seasonal plasticity of auditory hair cell frequency sensitivity correlates with plasma steroid levels in vocal fish

    OpenAIRE

    Rohmann, Kevin N.; Bass, Andrew H.

    2011-01-01

    Vertebrates displaying seasonal shifts in reproductive behavior provide the opportunity to investigate bidirectional plasticity in sensory function. The midshipman teleost fish exhibits steroid-dependent plasticity in frequency encoding by eighth nerve auditory afferents. In this study, evoked potentials were recorded in vivo from the saccule, the main auditory division of the inner ear of most teleosts, to test the hypothesis that males and females exhibit seasonal changes in hair cell physi...

  12. Electrically evoked auditory nerve responses in the cochlea with normal outer hair cells

    OpenAIRE

    Ren, Tianying; Guo, Menghe; He, Wenxuan; Miller, Josef M.; Nuttall, Alfred L.

    2009-01-01

    As hybrid cochlear implant devices are increasingly used for restoring hearing in patients with residual hearing it is important to understand electrically evoked responses in cochleae having functional hair cells. To test the hypothesis that extracochlear electrical stimulation (EES) from sinusoidal current can provoke an auditory nerve response with normal frequency selectivity, the EES-evoked compound action potential (ECAP) was investigated in this study. Brief sinusoidal electrical curre...

  13. Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome

    Directory of Open Access Journals (Sweden)

    Mohi Ahmed

    2015-09-01

    Full Text Available WHSC1 is a histone methyltransferase (HMT that catalyses the addition of methyl groups to lysine 36 on histone 3. In humans, WHSC1 haploinsufficiency is associated with all known cases of Wolf-Hirschhorn syndrome (WHS. The cardinal feature of WHS is a craniofacial dysmorphism, which is accompanied by sensorineural hearing loss in 15% of individuals with WHS. Here, we show that WHSC1-deficient mice display craniofacial defects that overlap with WHS, including cochlea anomalies. Although auditory hair cells are specified normally, their stereocilia hair bundles required for sound perception fail to develop the appropriate morphology. Furthermore, the orientation and cellular organisation of cochlear hair cells and their innervation are defective. These findings identify, for the first time, the likely cause of sensorineural hearing loss in individuals with WHS.

  14. Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear.

    Directory of Open Access Journals (Sweden)

    Yves Brand

    Full Text Available Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.

  15. AUDITORY HAIR CELL EXPLANT CO-CULTURES PROMOTE THE DIFFERENTIATION OF STEM CELLS INTO BIPOLAR NEURONS

    OpenAIRE

    Coleman, B.; Fallon, J. B.; Gillespie, L.N.; Silva, M.G.; Shepherd, R.K.

    2006-01-01

    Auditory neurons, the target neurons of the cochlear implant, degenerate following a sensorineural hearing loss. The goal of this research is to direct the differentiation of embryonic stem cells (SCs) into bipolar auditory neurons that can be used to replace degenerating neurons in the deafened mammalian cochlea. Successful replacement of auditory neurons is likely to result in improved clinical outcomes for cochlear implant recipients. We examined two post-natal auditory co-culture models w...

  16. ROR1 is essential for proper innervation of auditory hair cells and hearing in humans and mice.

    Science.gov (United States)

    Diaz-Horta, Oscar; Abad, Clemer; Sennaroglu, Levent; Foster, Joseph; DeSmidt, Alexandra; Bademci, Guney; Tokgoz-Yilmaz, Suna; Duman, Duygu; Cengiz, F Basak; Grati, M'hamed; Fitoz, Suat; Liu, Xue Z; Farooq, Amjad; Imtiaz, Faiqa; Currall, Benjamin B; Morton, Cynthia Casson; Nishita, Michiru; Minami, Yasuhiro; Lu, Zhongmin; Walz, Katherina; Tekin, Mustafa

    2016-05-24

    Hair cells of the inner ear, the mechanosensory receptors, convert sound waves into neural signals that are passed to the brain via the auditory nerve. Little is known about the molecular mechanisms that govern the development of hair cell-neuronal connections. We ascertained a family with autosomal recessive deafness associated with a common cavity inner ear malformation and auditory neuropathy. Via whole-exome sequencing, we identified a variant (c.2207G>C, p.R736T) in ROR1 (receptor tyrosine kinase-like orphan receptor 1), cosegregating with deafness in the family and absent in ethnicity-matched controls. ROR1 is a tyrosine kinase-like receptor localized at the plasma membrane. At the cellular level, the mutation prevents the protein from reaching the cellular membrane. In the presence of WNT5A, a known ROR1 ligand, the mutated ROR1 fails to activate NF-κB. Ror1 is expressed in the inner ear during development at embryonic and postnatal stages. We demonstrate that Ror1 mutant mice are severely deaf, with preserved otoacoustic emissions. Anatomically, mutant mice display malformed cochleae. Axons of spiral ganglion neurons show fasciculation defects. Type I neurons show impaired synapses with inner hair cells, and type II neurons display aberrant projections through the cochlear sensory epithelium. We conclude that Ror1 is crucial for spiral ganglion neurons to innervate auditory hair cells. Impairment of ROR1 function largely affects development of the inner ear and hearing in humans and mice. PMID:27162350

  17. Two adaptation processes in auditory hair cells together can provide an active amplifier

    CERN Document Server

    Vilfan, A; Vilfan, Andrej; Duke, Thomas

    2003-01-01

    The hair cells of the vertebrate inner ear convert mechanical stimuli to electrical signals. Two adaptation mechanisms are known to modify the ionic current flowing through the transduction channels of the hair bundles: a rapid process involves calcium ions binding to the channels; and a slower adaptation is associated with the movement of myosin motors. We present a mathematical model of the hair cell which demonstrates that the combination of these two mechanisms can produce `self-tuned critical oscillations', i.e. maintain the hair bundle at the threshold of an oscillatory instability. The characteristic frequency depends on the geometry of the bundle and on the calcium dynamics, but is independent of channel kinetics. Poised on the verge of vibrating, the hair bundle acts as an active amplifier. However, if the hair cell is sufficiently perturbed, other dynamical regimes can occur. These include slow relaxation oscillations which resemble the hair bundle motion observed in some experimental preparations.

  18. Hair cell ribbon synapses

    OpenAIRE

    Moser, Tobias; Brandt, Andreas; Lysakowski, Anna

    2006-01-01

    Hearing and balance rely on the faithful synaptic coding of mechanical input by the auditory and vestibular hair cells of the inner ear. Mechanical deflection of their stereocilia causes the opening of mechanosensitive channels, resulting in hair cell depolarization, which controls the release of glutamate at ribbon-type synapses. Hair cells have a compact shape with strong polarity. Mechanoelectrical transduction and active membrane turnover associated with stereociliar renewal dominate the ...

  19. Loss of auditory sensitivity from inner hair cell synaptopathy can be centrally compensated in the young but not old brain.

    Science.gov (United States)

    Möhrle, Dorit; Ni, Kun; Varakina, Ksenya; Bing, Dan; Lee, Sze Chim; Zimmermann, Ulrike; Knipper, Marlies; Rüttiger, Lukas

    2016-08-01

    A dramatic shift in societal demographics will lead to rapid growth in the number of older people with hearing deficits. Poorer performance in suprathreshold speech understanding and temporal processing with age has been previously linked with progressing inner hair cell (IHC) synaptopathy that precedes age-dependent elevation of auditory thresholds. We compared central sound responsiveness after acoustic trauma in young, middle-aged, and older rats. We demonstrate that IHC synaptopathy progresses from middle age onward and hearing threshold becomes elevated from old age onward. Interestingly, middle-aged animals could centrally compensate for the loss of auditory fiber activity through an increase in late auditory brainstem responses (late auditory brainstem response wave) linked to shortening of central response latencies. In contrast, old animals failed to restore central responsiveness, which correlated with reduced temporal resolution in responding to amplitude changes. These findings may suggest that cochlear IHC synaptopathy with age does not necessarily induce temporal auditory coding deficits, as long as the capacity to generate neuronal gain maintains normal sound-induced central amplitudes. PMID:27318145

  20. Effect of stress on the membrane capacitance of the auditory outer hair cell.

    OpenAIRE

    Iwasa, K H

    1993-01-01

    The membrane capacitance of the outer hair cell, which has unique membrane potential-dependent motility, was monitored during application of membrane tension. It was found that the membrane capacitance of the cell decreased when stress was applied to the membrane. This result is the opposite of stretching the lipid bilayer in the plasma membrane. It thus indicates the importance of some other capacitance component that decreases on stretching. It has been known that charge movement across the...

  1. The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells.

    Science.gov (United States)

    Pepermans, Elise; Michel, Vincent; Goodyear, Richard; Bonnet, Crystel; Abdi, Samia; Dupont, Typhaine; Gherbi, Souad; Holder, Muriel; Makrelouf, Mohamed; Hardelin, Jean-Pierre; Marlin, Sandrine; Zenati, Akila; Richardson, Guy; Avan, Paul; Bahloul, Amel; Petit, Christine

    2014-07-01

    Protocadherin-15 (Pcdh15) is a component of the tip-links, the extracellular filaments that gate hair cell mechano-electrical transduction channels in the inner ear. There are three Pcdh15 splice isoforms (CD1, CD2 and CD3), which only differ by their cytoplasmic domains; they are thought to function redundantly in mechano-electrical transduction during hair-bundle development, but whether any of these isoforms composes the tip-link in mature hair cells remains unknown. By immunolabelling and both morphological and electrophysiological analyses of post-natal hair cell-specific conditional knockout mice (Pcdh15ex38-fl/ex38-fl Myo15-cre+/-) that lose only this isoform after normal hair-bundle development, we show that Pcdh15-CD2 is an essential component of tip-links in mature auditory hair cells. The finding, in the homozygous or compound heterozygous state, of a PCDH15 frameshift mutation (p.P1515Tfs*4) that affects only Pcdh15-CD2, in profoundly deaf children from two unrelated families, extends this conclusion to humans. These results provide key information for identification of new components of the mature auditory mechano-electrical transduction machinery. This will also serve as a basis for the development of gene therapy for deafness caused by PCDH15 defects. PMID:24940003

  2. Developmental regulation of planar cell polarity and hair-bundle morphogenesis in auditory hair cells: lessons from human and mouse genetics.

    Science.gov (United States)

    Lu, Xiaowei; Sipe, Conor W

    2016-01-01

    Hearing loss is the most common and costly sensory defect in humans and genetic causes underlie a significant proportion of affected individuals. In mammals, sound is detected by hair cells (HCs) housed in the cochlea of the inner ear, whose function depends on a highly specialized mechanotransduction organelle, the hair bundle. Understanding the factors that regulate the development and functional maturation of the hair bundle is crucial for understanding the pathophysiology of human deafness. Genetic analysis of deafness genes in animal models, together with complementary forward genetic screens and conditional knock-out mutations in essential genes, have provided great insights into the molecular machinery underpinning hair-bundle development and function. In this review, we highlight recent advances in our understanding of hair-bundle morphogenesis, with an emphasis on the molecular pathways governing hair-bundle polarity and orientation. We next discuss the proteins and structural elements important for hair-cell mechanotransduction as well as hair-bundle cohesion and maintenance. In addition, developmental signals thought to regulate tonotopic features of HCs are introduced. Finally, novel approaches that complement classic genetics for studying the molecular etiology of human deafness are presented. WIREs Dev Biol 2016, 5:85-101. doi: 10.1002/wdev.202 For further resources related to this article, please visit the WIREs website. PMID:26265594

  3. Too much of a good thing: Long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity

    OpenAIRE

    Chen, Guang-Di; Kermany, Mohammad Habiby; D’Elia, Alessandra; Ralli, Massimo; Tanaka, Chiemi; Bielefeld, Eric C.; Ding, Dalian; Henderson, Donald; Salvi, Richard

    2010-01-01

    Aspirin has been extensively used in clinical settings. Its side effects on auditory function, including hearing loss and tinnitus, are considered as temporary. A recent promising finding is that chronic treatment with high-dose salicylate (the active ingredient of aspirin) for several weeks enhances expression of the outer hair cell (OHC) motor protein (prestin), resulting in strengthened OHC electromotility and enhanced distortion product otoacoustic emissions (DPOAE). To follow up on these...

  4. A phenomenological model of the synapse between the inner hair cell and auditory nerve: Long-term adaptation with power-law dynamics

    OpenAIRE

    Zilany, Muhammad S.A.; Bruce, Ian C.; Nelson, Paul C.; Carney, Laurel H.

    2009-01-01

    There is growing evidence that the dynamics of biological systems that appear to be exponential over short time courses are in some cases better described over the long-term by power-law dynamics. A model of rate adaptation at the synapse between inner hair cells and auditory-nerve (AN) fibers that includes both exponential and power-law dynamics is presented here. Exponentially adapting components with rapid and short-term time constants, which are mainly responsible for shaping onset respon...

  5. Expression of amyloid-β in mouse cochlear hair cells causes an early-onset auditory defect in high-frequency sound perception.

    Science.gov (United States)

    Omata, Yasuhiro; Tharasegaran, Suganya; Lim, Young-Mi; Yamasaki, Yasutoyo; Ishigaki, Yasuhito; Tatsuno, Takanori; Maruyama, Mitsuo; Tsuda, Leo

    2016-03-01

    Increasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods. To establish a new mouse AD model that takes advantage of this benefit, we produced transgenic mice expressing amyloid-β (Aβ), a causative element for AD, in their auditory hair cells. Electrophysiological assessment indicated that these mice had hearing impairment, specifically in high-frequency sound perception (>32 kHz), at 4 months after birth. Furthermore, loss of hair cells in the basal region of the cochlea, which is known to be associated with age-related hearing loss, appeared to be involved in this hearing defect. Interestingly, overexpression of human microtubule-associated protein tau, another factor in AD development, synergistically enhanced the Aβ-induced hearing defects. These results suggest that our new system reflects some, if not all, aspects of AD progression and, therefore, could complement the traditional AD mouse model to monitor Aβ-induced neuronal dysfunction quantitatively over time. PMID:26959388

  6. Noise exposure modulates cochlear inner hair cell ribbon volumes, correlating with changes in auditory measures in the FVB/nJ mouse

    Science.gov (United States)

    Paquette, Stephen T.; Gilels, Felicia; White, Patricia M.

    2016-01-01

    Cochlear neuropathy resulting from unsafe noise exposure is a life altering condition that affects many people. This hearing dysfunction follows a conserved mechanism where inner hair cell synapses are lost, termed cochlear synaptopathy. Here we investigate cochlear synaptopathy in the FVB/nJ mouse strain as a prelude for the investigation of candidate genetic mutations for noise damage susceptibility. We used measurements of auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to assess hearing recovery in FVB/nJ mice exposed to two different noise levels. We also utilized confocal fluorescence microscopy in mapped whole mount cochlear tissue, in conjunction with deconvolution and three-dimensional modeling, to analyze numbers, volumes and positions of paired synaptic components. We find evidence for significant synapse reorganization in response to both synaptopathic and sub-synaptopathic noise exposures in FVB/nJ. Specifically, we find that the modulation in volume of very small synaptic ribbons correlates with the presence of reduced ABR peak one amplitudes in both levels of noise exposures. These experiments define the use of FVB/nJ mice for further genetic investigations into the mechanisms of noise damage. They further suggest that in the cochlea, neuronal-inner hair cell connections may dynamically reshape as part of the noise response. PMID:27162161

  7. Prospects for Replacement of Auditory Neurons by Stem Cells

    OpenAIRE

    Shi, Fuxin; Edge, Albert S. B.

    2013-01-01

    Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regene...

  8. Comparative transduction mechanisms of hair cells in the bullfrog uticulus. 2: Sensitivity and response dynamics to hair bundle displacement

    Science.gov (United States)

    Baird, Richard A.

    1994-01-01

    The present study was motivated by an interest in seeing whether hair cell types in the bullfrog utriculus might differ in their voltage responses to hair bundle displacement. Particular interest was in assessing the contributions of two factors to the responses of utricular hair cells. First, interest in examining the effect of hair bundle morphology on the sensitivity of hair cells to natural stimulation was motivated by the observation that vestibular hair cells, unlike many auditory hair cells, are not free-standing but rather linked to an accessory cupular or otolithic membrane via the tip of their kinocilium. Interest also laid in examining the contribution, if any, of adaptation to the response properties of utricular hair cells. Hair cells in auditory and vibratory inner ear endorgans adapt to maintained displacements of their hair bundles, sharply limiting their low frequency sensitivity. This adaptation is mediated by a shift in the displacement-response curve (DRC) of the hair cell along the displacement axis. Observations suggest that the adaptation process occurs within the hair bundle and precedes mechanoelectric transduction. Recent observations of time-dependent changes in hair bundle stiffness are consistent with this conclusion. Adaptation would be expected to be most useful in inner ear endorgans in which hair cells are subject to large static displacements that could potentially saturate their instantaneous response and compromise their sensitivity to high frequency stimulation. The adaptation process also permits hair cells to maintain their sensory hair bundle in the most sensitive portion of their DRC. In vestibular otolith organs in which static sensitivity is desirable, any adaptation process in the hair cells may be undesirable. The rate and extent of the decline of the voltage responses was measured of utricular hair cells to step and sinusoidal hair bundle displacements. Then for similar resting potentials and response amplitudes, the

  9. Relationship Between Hair Cell Loss and Hearing Loss in Fishes.

    Science.gov (United States)

    Smith, Michael E

    2016-01-01

    Exposure to intense sound or ototoxic chemicals can damage the auditory hair cells of vertebrates, resulting in hearing loss. Although the relationship between such hair cell damage and auditory function is fairly established for terrestrial vertebrates, there are limited data available to understand this relationship in fishes. Although investigators have measured either the morphological damage of the inner ear or the functional deficits in the hearing of fishes, very few have directly measured both in an attempt to find a relationship between the two. Those studies that have examined both auditory hair cell damage in the inner ear and the resulting hearing loss in fishes are reviewed here. In general, there is a significant linear relationship between the number of hair cells lost and the severity of hearing threshold shifts, although this varies between species and different hair cell-damaging stimuli. After trauma to the fish ear, auditory hair cells are able to regenerate to control level densities. With this regeneration also comes a restoration of hearing. Thus there is also a significant relationship between hair cell recovery and hearing recovery in fishes. PMID:26611069

  10. Characterization of adaptation motors in saccular hair cells by fluctuation analysis.

    OpenAIRE

    Frank, Jonathan E.; Markin, Vladislav; Jaramillo, Fernán

    2002-01-01

    The mechanical sensitivity of hair cells, the sensory receptors of the vestibular and auditory systems, is maintained by adaptation, which resets the transducer to cancel the effects of static stimuli. Adaptation motors in hair cells can be experimentally activated by externally applying a transduction channel blocker to the hair bundle, causing the hair bundle to move in the negative direction. We studied the variance in the position of the hair bundle during these displacements and found th...

  11. Prospects for replacement of auditory neurons by stem cells.

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    Shi, Fuxin; Edge, Albert S B

    2013-03-01

    Sensorineural hearing loss is caused by degeneration of hair cells or auditory neurons. Spiral ganglion cells, the primary afferent neurons of the auditory system, are patterned during development and send out projections to hair cells and to the brainstem under the control of largely unknown guidance molecules. The neurons do not regenerate after loss and even damage to their projections tends to be permanent. The genesis of spiral ganglion neurons and their synapses forms a basis for regenerative approaches. In this review we critically present the current experimental findings on auditory neuron replacement. We discuss the latest advances with a focus on (a) exogenous stem cell transplantation into the cochlea for neural replacement, (b) expression of local guidance signals in the cochlea after loss of auditory neurons, (c) the possibility of neural replacement from an endogenous cell source, and (d) functional changes from cell engraftment. PMID:23370457

  12. Ultrastructural analysis of aminoglycoside-induced hair cell death in the zebrafish lateral line reveals an early mitochondrial response.

    OpenAIRE

    Owens, Kelly,; Cunningham, Dale,; Macdonald, Glen; Rubel, Edwin,; Raible, David,; Pujol, Remy

    2007-01-01

    Loss of the mechanosensory hair cells in the auditory and vestibular organs leads to hearing and balance deficits. To investigate initial, in vivo events in aminoglycoside-induced hair cell damage, we examined hair cells from the lateral line of the zebrafish, Danio rerio. The mechanosensory lateral line is located externally on the animal and therefore allows direct manipulation and observation of hair cells. Labeling with vital dyes revealed a rapid response of hair cells to the aminoglycos...

  13. The Transcriptomics to Proteomics of Hair Cell Regeneration: Looking for a Hair Cell in a Haystack

    Directory of Open Access Journals (Sweden)

    Michael E. Smith

    2013-07-01

    Full Text Available Mature mammals exhibit very limited capacity for regeneration of auditory hair cells, while all non-mammalian vertebrates examined can regenerate them. In an effort to find therapeutic targets for deafness and balance disorders, scientists have examined gene expression patterns in auditory tissues under different developmental and experimental conditions. Microarray technology has allowed the large-scale study of gene expression profiles (transcriptomics at whole-genome levels, but since mRNA expression does not necessarily correlate with protein expression, other methods, such as microRNA analysis and proteomics, are needed to better understand the process of hair cell regeneration. These technologies and some of the results of them are discussed in this review. Although there is a considerable amount of variability found between studies owing to different species, tissues and treatments, there is some concordance between cellular pathways important for hair cell regeneration. Since gene expression and proteomics data is now commonly submitted to centralized online databases, meta-analyses of these data may provide a better picture of pathways that are common to the process of hair cell regeneration and lead to potential therapeutics. Indeed, some of the proteins found to be regulated in the inner ear of animal models (e.g., IGF-1 have now gone through human clinical trials.

  14. Review of hair follicle dermal cells

    OpenAIRE

    Yang, Chao-Chun; Cotsarelis, George

    2010-01-01

    Hair follicle stem cells in the epithelial bulge are responsible for the continual regeneration of the hair follicle during cycling. The bulge cells reside in a niche composed of dermal cells. The dermal compartment of the hair follicle consists of the dermal papilla and dermal sheath. Interactions between hair follicle epithelial and dermal cells are necessary for hair follicle morphogenesis during development and in hair reconstitution assays. Dermal papilla and dermal sheath cells express ...

  15. Hair cell regeneration: Look to the future

    Science.gov (United States)

    Rubel, Edwin W.

    2005-04-01

    Less than 2 decades ago it was discovered that birds can regenerate hair cells in the auditory and vestibular parts of the inner ear after the native hair cells are destroyed by exposure to excessive noise or by mechanical trauma of aminoglycoside antibiotics. This discovery issued in a new era of hearing research-it suggested that some day it may be possible to actually restore hearing in people with congenital or acquired hearing loss due to the degeneration of sensory cells or supporting cells in the inner ear. Fifteen years is a very short time in the history of science. Consider the fact that we have actively sought chemical treatments to prevent or cure cancers for well over a half century and the ``war on Cancer,'' resulted in enormous public and private support. Progress has been great, and some forms of cancer can be treated with great success, but the overall 5-year survival rates have only risen from about 50% to 63%. Progress will continue and many more forms of cancer will be cured and prevented during the next half century. Similarly, during the first 15 years of hair cell regeneration research enormous progress has been made, and we now know that postnatal mammalian ears have the capacity to produce new hair cells. We are indeed a long way from restoring hearing through hair cell regeneration, but the future is pretty clear. I will review the progress of this field with an eye toward the future and what it means for treatments of today. In particular, I will address the potential cost versus benefits of bilateral implantation when applied to babies and young children.

  16. Hair follicle stem cells and intrafollicular homeostasis

    OpenAIRE

    Alp Can

    2014-01-01

    A hair follicle is the primary unit that produces a single outgrowing visible hair shaft. All hair follicles have a regeneration cycle consisting growth, destruction and resting phase, all of which are controlled by several intrinsic and extrinsic mechanisms. All hair forming cell populations arise from hair follicle stem cells that are located in bulge and hair germ. Epithelial progenitors themselves surround a core cluster of mesenchymal cells, the dermal papilla, which is thought to provid...

  17. Supporting cells eliminate dying sensory hair cells to maintain epithelial integrity in the avian inner ear

    OpenAIRE

    Bird, Jonathan E.; Daudet, Nicolas; Mark E Warchol; Gale, Jonathan E.

    2010-01-01

    Epithelial homeostasis is essential for sensory transduction in the auditory and vestibular organs of the inner ear, but how it is maintained during trauma is poorly understood. To examine potential repair mechanisms, we expressed β-actin-EGFP in the chick inner ear and used live-cell imaging to study how sensory epithelia responded during aminoglycoside-induced hair cell trauma. We found that glial-like supporting cells used two independent mechanisms to rapidly eliminate dying hair cells. S...

  18. Dimethyl Sulfoxide (DMSO) Exacerbates Cisplatin-induced Sensory Hair Cell Death in Zebrafish (Danio rerio)

    OpenAIRE

    Uribe, Phillip M.; Mueller, Melissa A.; Gleichman, Julia S.; Kramer, Matthew D.; Qi Wang; Martha Sibrian-Vazquez; Strongin, Robert M.; Peter S Steyger; Douglas A Cotanche; Matsui, Jonathan I.

    2013-01-01

    Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under ...

  19. Effect of histone deacetylase inhibitors trichostatin A and valproic acid on hair cell regeneration in zebrafish lateral line neuromasts

    OpenAIRE

    Chengfu Cai; Huawei Li

    2014-01-01

    In humans, auditory hair cells are not replaced when injured. Thus, cochlear hair cell loss causes progressive and permanent hearing loss. Conversely, nonmammalian vertebrates are capable of regenerating lost sensory hair cells. The zebrafish lateral line has numerous qualities that make it well suited for studying hair cell development and regeneration. Histone deacetylase (HDAC) activity has been shown to have an important role in regenerative processes in vertebrates, but its function in h...

  20. Effect of histone deacetylase inhibitors trichostatin A and valproic acid on hair cell regeneration in zebrafish lateral line neuromasts

    OpenAIRE

    He, Yingzi; Cai, Chengfu; Tang, Dongmei; Sun, Shan; Li, Huawei

    2014-01-01

    In humans, auditory hair cells are not replaced when injured. Thus, cochlear hair cell loss causes progressive and permanent hearing loss. Conversely, non-mammalian vertebrates are capable of regenerating lost sensory hair cells. The zebrafish lateral line has numerous qualities that make it well-suited for studying hair cell development and regeneration. Histone deacetylase (HDAC) activity has been shown to have an important role in regenerative processes in vertebrates, but its function in ...

  1. Restoration of auditory evoked responses by human ES cell-derived otic progenitors

    OpenAIRE

    Chen, Wei; Jongkamonwiwat, Nopporn; Abbas, Leila; Eshtan, Sarah Jacob; Johnson, Stuart L.; Kuhn, Stephanie; Milo, Marta; Thurlow, Johanna K.; Peter W Andrews; Marcotti, Walter; Moore, Harry D.; Rivolta, Marcelo N

    2012-01-01

    Deafness is a condition with a high prevalence worldwide, produced primarily by the loss of the sensory hair cells and their associated spiral ganglion neurons (SGNs). Of all the forms of deafness, auditory neuropathy is of a particular concern. This condition, defined primarily by damage to the SGNs with relative preservation of the hair cells 1 , is responsible for a substantial proportion of patients with hearing impairment 2 . While the loss of hair cells can be circumvented partially by ...

  2. Solitary Hair Cells Are Distributed Throughout the Extramacular Epithelium in the Bullfrog's Saccule

    OpenAIRE

    Gale, Jonathan E.; Meyers, Jason R.; Corwin, Jeffrey T.

    2000-01-01

    The frog inner ear contains eight sensory organs that provide sensitivities to auditory, vestibular, and ground-borne vibrational stimuli. The saccule in bullfrogs is responsible for detecting ground- and air-borne vibrations and is used for studies of hair cell physiology, development, and regeneration. Based on hair bundle morphology, a number of hair cell types have been defined in this organ. Using immunocytochemistry, vital labeling, and electron microscopy, we have characterized a new h...

  3. Hair Cell Overexpression of Islet1 Reduces Age-Related and Noise-Induced Hearing Loss

    OpenAIRE

    Huang, Mingqian; Kantardzhieva, Albena; Scheffer, Deborah; Liberman, M. Charles; Chen, Zheng-Yi

    2013-01-01

    Isl1 is a LIM-homeodomain transcription factor that is critical in the development and differentiation of multiple tissues. In the mouse inner ear, Isl1 is expressed in the prosensory region of otocyst, in young hair cells and supporting cells, and is no longer expressed in postnatal auditory hair cells. To evaluate how continuous Isl1 expression in postnatal hair cells affects hair cell development and cochlear function, we created a transgenic mouse model in which the Pou4f3 promoter drives...

  4. Efferent control of the electrical and mechanical properties of hair cells in the bullfrog's sacculus.

    Directory of Open Access Journals (Sweden)

    Manuel Castellano-Muñoz

    Full Text Available BACKGROUND: Hair cells in the auditory, vestibular, and lateral-line systems respond to mechanical stimulation and transmit information to afferent nerve fibers. The sensitivity of mechanoelectrical transduction is modulated by the efferent pathway, whose activity usually reduces the responsiveness of hair cells. The basis of this effect remains unknown. METHODOLOGY AND PRINCIPAL FINDINGS: We employed immunocytological, electrophysiological, and micromechanical approaches to characterize the anatomy of efferent innervation and the effect of efferent activity on the electrical and mechanical properties of hair cells in the bullfrog's sacculus. We found that efferent fibers form extensive synaptic terminals on all macular and extramacular hair cells. Macular hair cells expressing the Ca(2+-buffering protein calretinin contain half as many synaptic ribbons and are innervated by twice as many efferent terminals as calretinin-negative hair cells. Efferent activity elicits inhibitory postsynaptic potentials in hair cells and thus inhibits their electrical resonance. In hair cells that exhibit spiking activity, efferent stimulation suppresses the generation of action potentials. Finally, efferent activity triggers a displacement of the hair bundle's resting position. CONCLUSIONS AND SIGNIFICANCE: The hair cells of the bullfrog's sacculus receive a rich efferent innervation with the heaviest projection to calretinin-containing cells. Stimulation of efferent axons desensitizes the hair cells and suppresses their spiking activity. Although efferent activation influences mechanoelectrical transduction, the mechanical effects on hair bundles are inconsistent.

  5. Effect of voltage dynamics on response properties in a model of sensory hair cell

    CERN Document Server

    Amro, Rami

    2012-01-01

    Sensory hair cells in auditory and vestibular organs rely on active mechanisms to achieve high sensitivity and frequency selectivity. Recent experimental studies have documented self-sustained oscillations in hair cells of lower vertebrates on two distinct levels. First, the hair bundle can undergo spontaneous mechanical oscillations. Second, somatic electric voltage oscillations across the baso-lateral membrane of the hair cell have been observed. We develop a biophysical model of the bullfrog's saccular hair cell consisting of two compartments, mechanical and electrical, to study how the mechanical and the voltage oscillations interact to produce coherent self-sustained oscillations and how this interaction contributes to the overall sensitivity and selectivity of the hair cell. The model incorporates nonlinear mechanical stochastic hair bundle system coupled bi-directionally to a Hodgkin-Huxley type system describing somatic ionic currents. We isolate regions of coherent spontaneous oscillations in the par...

  6. Mammalin cochlear supporting cells transdifferentiation into outer hair cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To study the recovery of the outer hair cells in the bat cochlea after gentamicin exposure. Methods Bats were injected with a daily dose of gentamicin for 15 consecutive days and bromodeoxyuridine (BrdU) was given from day 16 to day 40 of this recovery phase. Hearing was assessed by overt acoustic behavior and auditory brainstem responses analysis, which was performed one day prior to the first injection and a day after the last injection (day 16). On day 40 animals were sacrificed for detection o...

  7. Mammalin cochlear supporting cells transdifferentiation into outer hair cells

    Institute of Scientific and Technical Information of China (English)

    Liu Siwei; Zhang Shaoqiang; Zhu Hongliang; Li Baiya; Zheng Qingyin; Li Shengli

    2008-01-01

    Objective To study the recovery of the outer hair cells in the bat cochlea after gentamicin exposure.Methods Bats were injected with a daily dose of gentamicin for 15 consecutive days and bromodeoxyuridine (BrdU)was given from day 16 to day 40 of this recovery phase. Hearing was assessed by overt acoustic behavior and auditory brainstem responses analysis, which was performed one day prior to the first injection and a day after the last injection (day 16). On day 40 animals were sacrificed for detection of cells that could take up BrdU. Results After 15 days of gentamicin treatment, all of the animals were proved to be deafened with significant increases of ABR thresholds,compared with control group. The findings in immunocytochemical stained samples and scanning electron microscopy revealed that BrdU labeled nuclei were observed in the cochlea in all of the deafened animals most commonly in the regions of the first-row and second-row Deiter's cells (DCs) and occasionally in the regions of the third-ruw DCs.Conclusion We suggest that, under sufficient drug and enough time, the bat cochlear supporting cells can directly transdifferentiate into the outer hair cells after aminoglycoside exposure. This transdifferentation process is essential for repair of outer hair cells and recovery of normal function after gentamicin exposure.

  8. Hearing aid and Hair cell

    Directory of Open Access Journals (Sweden)

    Zahra Jafari

    2001-05-01

    Full Text Available We expect some people benefit more from their hearing aids, but after a while they complain of inappropriate loudness growth.  Currently fitting hearing aids based on their loudness growth curves one of the best and most acceptable ways of fitting hearing aids; we should study this curve based on the disturbed function of inner and outer hair cells. We should also know that based on which curves can make the growth curve of the damaged cells to normal ones.

  9. An Open Loop Feed-Forward Control Scheme for Bioinspired Artificial Hair Cell Sensors

    OpenAIRE

    Crowley, Kevin Michael

    2015-01-01

    This research documents the creation and use of an open-loop feed forward control scheme designed to manipulate the DC potential across lipid bilayer membranes in artificial hair cell sensors. Inspired by the human cochlea's non-linear gain phenomenon, whereby the cochlea can increase or decrease the effective gain of the auditory system, this controller is the first step in developing more sophisticated signal processing schemes for use with future bio-inspired artificial hair cell developme...

  10. Hair cell damage recruited Lgr5-expressing cells are hair cell progenitors in neonatal mouse utricle

    Directory of Open Access Journals (Sweden)

    Jinchao Lin

    2015-04-01

    Full Text Available Damage-activated stem/progenitor cells play important roles in regenerating lost cells and in tissue repair. Previous studies reported that the mouse utricle has limited hair cell regeneration ability after hair cell ablation. However, the potential progenitor cell population regenerating new hair cells remains undiscovered. In this study, we first found that Lgr5, a Wnt target gene that is not usually expressed in the neonatal mouse utricle, can be activated by 24 hour neomycin treatment in a sub-population of supporting cells in the striolar region of the neonatal mouse utricle. Lineage tracing demonstrated that these Lgr5-positive supporting cells could regenerate new hair cells in explant culture. We isolated the damage-activated Lgr5-positive cells with flow cytometry and found that these Lgr5-positive supporting cells could regenerate hair cells in vitro, and self-renew to form spheres, which maintained the capacity to differentiate into hair cells over seven generations of passages. Our results suggest that damage-activated Lgr5-positive supporting cells act as hair cell progenitors in the neonatal mouse utricle, which may help to uncover a potential route to regenerate hair cell in mammals.

  11. Human hair genealogies and stem cell latency

    Directory of Open Access Journals (Sweden)

    Tavaré Simon

    2006-02-01

    Full Text Available Abstract Background Stem cells divide to reproduce themselves and produce differentiated progeny. A fundamental problem in human biology has been the inability to measure how often stem cells divide. Although it is impossible to observe every division directly, one method for counting divisions is to count replication errors; the greater the number of divisions, the greater the numbers of errors. Stem cells with more divisions should produce progeny with more replication errors. Methods To test this approach, epigenetic errors (methylation in CpG-rich molecular clocks were measured from human hairs. Hairs exhibit growth and replacement cycles and "new" hairs physically reappear even on "old" heads. Errors may accumulate in long-lived stem cells, or in their differentiated progeny that are eventually shed. Results Average hair errors increased until two years of age, and then were constant despite decades of replacement, consistent with new hairs arising from infrequently dividing bulge stem cells. Errors were significantly more frequent in longer hairs, consistent with long-lived but eventually shed mitotic follicle cells. Conclusion Constant average hair methylation regardless of age contrasts with the age-related methylation observed in human intestine, suggesting that error accumulation and therefore stem cell latency differs among tissues. Epigenetic molecular clocks imply similar mitotic ages for hairs on young and old human heads, consistent with a restart with each new hair, and with genealogies surreptitiously written within somatic cell genomes.

  12. Improved biolistic transfection of hair cells.

    Directory of Open Access Journals (Sweden)

    Hongyu Zhao

    Full Text Available Transient transfection of hair cells has proven challenging. Here we describe modifications to the Bio-Rad Helios Gene Gun that, along with an optimized protocol, improve transfection of bullfrog, chick, and mouse hair cells. The increased penetrating power afforded by our method allowed us to transfect mouse hair cells from the basal side, through the basilar membrane; this configuration protects hair bundles from damage during the procedure. We characterized the efficiency of transfection of mouse hair cells with fluorescently-tagged actin fusion protein using both the optimized procedure and a published procedure; while the efficiency of the two methods was similar, the morphology of transfected hair cells was improved with the new procedure. In addition, using the improved method, we were able to transfect hair cells in the bullfrog sacculus and chick cochlea for the first time. We used fluorescent-protein fusions of harmonin b (USH1C and PMCA2 (ATP2B2; plasma-membrane Ca(2+-ATPase isoform 2 to examine protein distribution in hair cells. While PMCA2-EGFP localization was similar to endogenous PMCA2 detected with antibodies, high levels of harmonin-EGFP were found at stereocilia tapers in bullfrog and chick, but not mouse; by contrast, harmonin-EGFP was concentrated in stereocilia tips in mouse hair cells.

  13. Myosin Light-Chain Kinase Is Necessary for Membrane Homeostasis in Cochlear Inner Hair Cells

    OpenAIRE

    Zhu, Guang-Jie; Wang, Fang; Chen, Chen; Xu, Lin; Zhang, Wen-Cheng; Fan, Chi; PENG, YA-JING; Chen, Jie; He, Wei-Qi; Guo, Shi-Ying; Zuo, Jian; Gao, Xia; Zhu, Min-Sheng

    2012-01-01

    The structural homeostasis of the cochlear hair cell membrane is critical for all aspects of sensory transduction, but the regulation of its maintenance is not well understood. In this report, we analyzed the cochlear hair cells of mice with specific deletion of myosin light chain kinase (MLCK) in inner hair cells. MLCK-deficient mice showed impaired hearing, with a 5- to 14-dB rise in the auditory brainstem response (ABR) thresholds to clicks and tones of different frequencies and a signific...

  14. Cell proliferation and hair cell addition in the ear of the goldfish, Carassius auratus

    Science.gov (United States)

    Lanford, P. J.; Presson, J. C.; Popper, A. N.

    1996-01-01

    Cell proliferation and hair cell addition have not been studied in the ears of otophysan fish, a group of species who have specialized hearing capabilities. In this study we used the mitotic S-phase marker bromodeoxyuridine (BrdU) to identify proliferating cells in the ear of one otophysan species, Carassius auratus (the goldfish). Animals were sacrificed at 3 h or 5 days postinjection with BrdU and processed for immunocytochemistry. The results of the study show that cell proliferation occurs in all of the otic endorgans and results in the addition of new hair cells. BrdU-labeled cells were distributed throughout all epithelia, including the primary auditory endorgan (saccule), where hair cell phenotypes vary considerably along the rostrocaudal axis. This study lays the groundwork for our transmission electron microscopy study of proliferative cells in the goldfish ear (Presson et al., Hearing Research 100 (1996) 10-20) as well as future studies of hair cell development in this species. The ability to predict, based on epithelial location, the future phenotype of developing hair cells in the saccule of the goldfish make that endorgan a particularly powerful model system for the investigation of early hair cell differentiation.

  15. Innervation of Cochlear Hair Cells by Human Induced Pluripotent Stem Cell-Derived Neurons In Vitro

    Science.gov (United States)

    Gunewardene, Niliksha; Crombie, Duncan; Dottori, Mirella; Nayagam, Bryony A.

    2016-01-01

    Induced pluripotent stem cells (iPSCs) may serve as an autologous source of replacement neurons in the injured cochlea, if they can be successfully differentiated and reconnected with residual elements in the damaged auditory system. Here, we explored the potential of hiPSC-derived neurons to innervate early postnatal hair cells, using established in vitro assays. We compared two hiPSC lines against a well-characterized hESC line. After ten days' coculture in vitro, hiPSC-derived neural processes contacted inner and outer hair cells in whole cochlear explant cultures. Neural processes from hiPSC-derived neurons also made contact with hair cells in denervated sensory epithelia explants and expressed synapsin at these points of contact. Interestingly, hiPSC-derived neurons cocultured with hair cells at an early stage of differentiation formed synapses with a higher number of hair cells, compared to hiPSC-derived neurons cocultured at a later stage of differentiation. Notable differences in the innervation potentials of the hiPSC-derived neurons were also observed and variations existed between the hiPSC lines in their innervation efficiencies. Collectively, these data illustrate the promise of hiPSCs for auditory neuron replacement and highlight the need to develop methods to mitigate variabilities observed amongst hiPSC lines, in order to achieve reliable clinical improvements for patients. PMID:26966437

  16. Hair cell heterogeneity and ultrasonic hearing: recent advances in understanding fish hearing.

    OpenAIRE

    Popper, A N

    2000-01-01

    The past decade has seen a wealth of new data on the auditory capabilities and mechanisms of fishes. We now have a significantly better appreciation of the structure and function of the auditory system in fishes with regard to their peripheral and central anatomy, physiology, behaviour, sound source localization and hearing capabilities. This paper deals with two of the newest of these findings, hair cell heterogeneity and the detection of ultrasound. As a result of this recent work, we now k...

  17. Restoration of auditory evoked responses by human ES-cell-derived otic progenitors.

    Science.gov (United States)

    Chen, Wei; Jongkamonwiwat, Nopporn; Abbas, Leila; Eshtan, Sarah Jacob; Johnson, Stuart L; Kuhn, Stephanie; Milo, Marta; Thurlow, Johanna K; Andrews, Peter W; Marcotti, Walter; Moore, Harry D; Rivolta, Marcelo N

    2012-10-11

    Deafness is a condition with a high prevalence worldwide, produced primarily by the loss of the sensory hair cells and their associated spiral ganglion neurons (SGNs). Of all the forms of deafness, auditory neuropathy is of particular concern. This condition, defined primarily by damage to the SGNs with relative preservation of the hair cells, is responsible for a substantial proportion of patients with hearing impairment. Although the loss of hair cells can be circumvented partially by a cochlear implant, no routine treatment is available for sensory neuron loss, as poor innervation limits the prospective performance of an implant. Using stem cells to recover the damaged sensory circuitry is a potential therapeutic strategy. Here we present a protocol to induce differentiation from human embryonic stem cells (hESCs) using signals involved in the initial specification of the otic placode. We obtained two types of otic progenitors able to differentiate in vitro into hair-cell-like cells and auditory neurons that display expected electrophysiological properties. Moreover, when transplanted into an auditory neuropathy model, otic neuroprogenitors engraft, differentiate and significantly improve auditory-evoked response thresholds. These results should stimulate further research into the development of a cell-based therapy for deafness. PMID:22972191

  18. Magnetic Force Nanoprobe for Direct Observation of Audio Frequency Tonotopy of Hair Cells.

    Science.gov (United States)

    Kim, Ji-Wook; Lee, Jae-Hyun; Ma, Ji-Hyun; Chung, Eunna; Choi, Hongsuh; Bok, Jinwoong; Cheon, Jinwoo

    2016-06-01

    Sound perception via mechano-sensation is a remarkably sensitive and fast transmission process, converting sound as a mechanical input to neural signals in a living organism. Although knowledge of auditory hair cell functions has advanced over the past decades, challenges remain in understanding their biomechanics, partly because of their biophysical complexity and the lack of appropriate probing tools. Most current studies of hair cells have been conducted in a relatively low-frequency range (perception of 20 kHz or higher. Here, we demonstrate that the magnetic force nanoprobe (MFN) has superb spatiotemporal capabilities to mechanically stimulate spatially-targeted individual hair cells with a temporal resolution of up to 9 μs, which is equivalent to approximately 50 kHz; therefore, it is possible to investigate avian hair cell biomechanics at different tonotopic regions of the cochlea covering a full hearing frequency range of 50 to 5000 Hz. We found that the variation of the stimulation frequency and amplitude of hair bundles creates distinct mechanical responsive features along the tonotopic axis, where the kinetics of the hair bundle recovery motion exhibits unique frequency-dependent characteristics: basal, middle, and apical hair bundles can effectively respond at their respective ranges of frequency. We revealed that such recovery kinetics possesses two different time constants that are closely related to the passive and active motilities of hair cells. The use of MFN is critical for the kinetics study of free-standing hair cells in a spatiotemporally distinct tonotopic organization. PMID:27215487

  19. Identification of the hair cell soma-1 antigen, HCS-1, as otoferlin.

    Science.gov (United States)

    Goodyear, Richard J; Legan, P Kevin; Christiansen, Jeffrey R; Xia, Bei; Korchagina, Julia; Gale, Jonathan E; Warchol, Mark E; Corwin, Jeffrey T; Richardson, Guy P

    2010-12-01

    Hair cells, the mechanosensitive receptor cells of the inner ear, are critical for our senses of hearing and balance. The small number of these receptor cells in the inner ear has impeded the identification and characterization of proteins important for hair cell function. The binding specificity of monoclonal antibodies provides a means for identifying hair cell-specific proteins and isolating them for further study. We have generated a monoclonal antibody, termed hair cell soma-1 (HCS-1), which specifically immunolabels hair cells in at least five vertebrate classes, including sharks and rays, bony fish, amphibians, birds, and mammals. We used HCS-1 to immunoprecipitate the cognate antigen and identified it as otoferlin, a member of the ferlin protein family. Mutations in otoferlin underlie DFNB9, a recessive, nonsyndromic form of prelingual deafness characterized as an auditory neuropathy. Using immunocytochemistry, we find that otoferlin is associated with the entire basolateral membrane of the hair cells and with vesicular structures distributed throughout most of the hair cell cytoplasm. Biochemical assays indicate that otoferlin is tightly associated with membranes, as it is not solubilized by alterations in calcium or salt concentrations. HCS-1 immunolabeling does not co-localize with ribeye, a constituent of synaptic ribbons, suggesting that otoferlin may, in addition to its proposed function in synaptic vesicle release, play additional roles in hair cells. PMID:20809368

  20. Conditioning the Cochlea to Facilitate Survival and Integration of Exogenous Cells into the Auditory Epithelium

    OpenAIRE

    Park, Yong-Ho; Wilson, Kevin F.; Ueda, Yoshihisa; Tung Wong, Hiu; Lisa A. Beyer; Donald L. Swiderski; Dolan, David F.; Raphael, Yehoash

    2014-01-01

    The mammalian auditory epithelium (AE) cannot replace supporting cells and hair cells once they are lost. Therefore, sensorineural hearing loss associated with missing cells is permanent. This inability to regenerate critical cell types makes the AE a potential target for cell replacement therapies such as stem cell transplantation. Inserting stem cells into the AE of deaf ears is a complicated task due to the hostile, high potassium environment of the scala media in the cochlea, and the robu...

  1. Comparative Transduction Mechanisms of Vestibular Otolith Hair Cells

    Science.gov (United States)

    Baird, Richard A.

    1994-01-01

    Hair cells in the bullfrog vestibular otolith organs regenerate following aminoglycoside ototoxicity. Hair cells in these organs are differentially sensitive to gentamicin, with saccular hair cells and hair cells in the utricular striola being damaged at lower gentamicin concentrations than hair cells in the utricular extrastriola. Regenerating hair cells in these organs have short hair bundles and can be classified into a number of phenotypes using the same morphological criteria used to identify their mature counterparts. Our studies suggest that some supporting cells can convert, or transdifferentiate,into hair cells without an intervening cell division. By stimulating these processes in humans, clinicians may be able to alleviate human deafness and peripheral vestibular disorders by regenerating and replacing lost hair cells. In vivo and in vitro studies were done on cell proliferation and hair cell regeneration.

  2. Organization of microtubules in cochlear hair cells.

    Science.gov (United States)

    Furness, D N; Hackney, C M; Steyger, P S

    1990-07-01

    The organization of microtubules in hair cells of the guinea-pig cochlea has been investigated using transmission electron microscopy and correlated with the location of tubulin-associated immunofluorescence in surface preparations of the organ of Corti. Results from both techniques reveal consistent distributions of microtubules in inner and outer hair cells. In the inner hair cells, microtubules are most concentrated in the apex. Reconstruction from serial sections shows three main groups: firstly, in channels through the cuticular plate and in a discontinuous belt around its upper perimeter; secondly, forming a ring inside a rim extending down from the lower perimeter of the plate; and thirdly, in a meshwork underlying the main body of the plate. In the cell body, microtubules line the inner face of the subsurface cistern and extend longitudinally through a tubulo-vesicular track between the apex and base. In outer hair cells, the pattern of microtubules associated with the cuticular plate is similar, although there are fewer present than in inner hair cells. In outer hair cells from the apex of the cochlea, microtubules occur around an infracuticular protrusion of cuticular plate material. In the cell body, many more microtubules occur in the region below the nucleus compared with inner hair cells. The possible functions of microtubules in hair cells are discussed by comparison with those found in other systems. These include morphogenesis and maintenance of cell shape; intracellular transport, e.g., of neurotransmitter vesicles; providing a possible substrate for motility; mechanical support of structures associated with sensory transduction. PMID:2197374

  3. Depletion of CD200+ Hair Follicle Stem Cells in Human Prematurely Gray Hair Follicles

    OpenAIRE

    Sujata Mohanty; Anil Kumar; Jyoti Dhawan; Vinod K Sharma; Somesh Gupta

    2013-01-01

    Introduction: Melanocyte stem cells (MelSCs) are known to be depleted in gray hair follicles. Hair follicle stem cells (HFSCs) are important for maintenance of stemness of MelSCs. Methods: We compared the proportion of CD200+ (Cluster of Differentiation 200 positive) stem cells in the outer root sheath cell suspension of gray and pigmented hair follicles of three patients with the premature graying of hair. In addition, explants culture for HFSCs was also carried out from gray and pigmented h...

  4. Optogenetic Control of Mouse Outer Hair Cells.

    Science.gov (United States)

    Wu, Tao; Ramamoorthy, Sripriya; Wilson, Teresa; Chen, Fangyi; Porsov, Edward; Subhash, Hrebesh; Foster, Sarah; Zhang, Yuan; Omelchenko, Irina; Bateschell, Michael; Wang, Lingyan; Brigande, John V; Jiang, Zhi-Gen; Mao, Tianyi; Nuttall, Alfred L

    2016-01-19

    Normal hearing in mammals depends on sound amplification by outer hair cells (OHCs) presumably by their somatic motility and force production. However, the role of OHC force production in cochlear amplification and frequency tuning are not yet fully understood. Currently, available OHC manipulation techniques for physiological or clinical studies are limited by their invasive nature, lack of precision, and poor temporal-spatial resolution. To overcome these limitations, we explored an optogenetic approach based on channelrhodopsin 2 (ChR-2), a direct light-activated nonselective cation channel originally discovered in Chlamydomonas reinhardtii. Three approaches were compared: 1) adeno-associated virus-mediated in utero transfer of the ChR-2 gene into the developing murine otocyst, 2) expression of ChR-2(H134R) in an auditory cell line (HEI-OC1), and 3) expression of ChR-2 in the OHCs of a mouse line carrying a ChR-2 conditional allele. Whole cell recording showed that blue light (470 nm) elicited the typical nonselective cation current of ChR-2 with reversal potential around zero in both mouse OHCs and HEI-OC1 cells and generated depolarization in both cell types. In addition, pulsed light stimulation (10 Hz) elicited a 1:1 repetitive depolarization and ChR-2 currents in mouse OHCs and HEI-OC1 cells, respectively. The time constant of depolarization in OHCs, 1.45 ms, is 10 times faster than HEI-OC1 cells, which allowed light stimulation up to rates of 10/s to elicit corresponding membrane potential changes. Our study demonstrates that ChR-2 can successfully be expressed in mouse OHCs and HEI-OC1 cells and that these present a typical light-sensitive current and depolarization. However, the amount of ChR-2 current induced in our in vivo experiments was insufficient to result in measurable cochlear effects. PMID:26789771

  5. Phoenix is required for mechanosensory hair cell regeneration in the zebrafish lateral line.

    Directory of Open Access Journals (Sweden)

    Martine Behra

    2009-04-01

    Full Text Available In humans, the absence or irreversible loss of hair cells, the sensory mechanoreceptors in the cochlea, accounts for a large majority of acquired and congenital hearing disorders. In the auditory and vestibular neuroepithelia of the inner ear, hair cells are accompanied by another cell type called supporting cells. This second cell population has been described as having stem cell-like properties, allowing efficient hair cell replacement during embryonic and larval/fetal development of all vertebrates. However, mammals lose their regenerative capacity in most inner ear neuroepithelia in postnatal life. Remarkably, reptiles, birds, amphibians, and fish are different in that they can regenerate hair cells throughout their lifespan. The lateral line in amphibians and in fish is an additional sensory organ, which is used to detect water movements and is comprised of neuroepithelial patches, called neuromasts. These are similar in ultra-structure to the inner ear's neuroepithelia and they share the expression of various molecular markers. We examined the regeneration process in hair cells of the lateral line of zebrafish larvae carrying a retroviral integration in a previously uncharacterized gene, phoenix (pho. Phoenix mutant larvae develop normally and display a morphologically intact lateral line. However, after ablation of hair cells with copper or neomycin, their regeneration in pho mutants is severely impaired. We show that proliferation in the supporting cells is strongly decreased after damage to hair cells and correlates with the reduction of newly formed hair cells in the regenerating phoenix mutant neuromasts. The retroviral integration linked to the phenotype is in a novel gene with no known homologs showing high expression in neuromast supporting cells. Whereas its role during early development of the lateral line remains to be addressed, in later larval stages phoenix defines a new class of proteins implicated in hair cell regeneration.

  6. Effect of histone deacetylase inhibitors trichostatin A and valproic acid on hair cell regeneration in zebrafish lateral line neuromasts

    Directory of Open Access Journals (Sweden)

    Yingzi eHe

    2014-11-01

    Full Text Available In humans, auditory hair cells are not replaced when injured. Thus, cochlear hair cell loss causes progressive and permanent hearing loss. Conversely, nonmammalian vertebrates are capable of regenerating lost sensory hair cells. The zebrafish lateral line has numerous qualities that make it well suited for studying hair cell development and regeneration. Histone deacetylase (HDAC activity has been shown to have an important role in regenerative processes in vertebrates, but its function in hair cell regeneration in vivo is not fully understood. Here, we have examined the role of HDAC activity in hair cell regeneration in the zebrafish lateral line. We eliminated lateral line hair cells of 5-day post-fertilization larvae using neomycin and then treated the larvae with HDAC inhibitors. To assess hair cell regeneration, we used 5-bromo-2-deoxyuridine (BrdU incorporation in zebrafish larvae to label mitotic cells after hair cell loss. We found that pharmacological inhibition of HDACs using trichostatin A (TSA or valproic acid (VPA increased histone acetylation in the regenerated neuromasts following neomycin-induced damage. We also showed that treatment with TSA or VPA decreased the number of supporting cells and regenerated hair cells in response to hair cell damage. Additionally, BrdU immunostaining and western blot analysis showed that TSA or VPA treatment caused a significant decrease in the percentage of S-phase cells and induced p21Cip1 and p27Kip1 expression, both of which are likely to explain the decrease in the amount of newly regenerated hair cells in treated embryos. Finally, we showed that HDAC inhibitors induced no observable cell death in neuromasts as measured by cleaved caspase-3 immunohistochemistry and western blot analysis. Taken together, our results demonstrate that HDAC activity has an important role in the regeneration of hair cells in the lateral line.

  7. Inhibition of caspases prevents ototoxic and ongoing hair cell death

    Science.gov (United States)

    Matsui, Jonathan I.; Ogilvie, Judith M.; Warchol, Mark E.

    2002-01-01

    Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment. Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

  8. Slow motility in hair cells of the frog amphibian papilla: Myosin light chain-mediated shape change

    OpenAIRE

    Farahbakhsh, Nasser A.; Narins, Peter M.

    2008-01-01

    Using video, fluorescence and confocal microscopy, quantitative analysis and modeling, we investigated intracellular processes mediating the calcium/calmodulin (Ca2+/CaM)-dependent slow motility in hair cells dissociated from the rostral region of amphibian papilla, one of the two auditory organs in frogs. The time course of shape changes in these hair cells during the period of pretreatment with several specific inhibitors, as well as their response to the calcium ionophore, ionomycin, were ...

  9. Perpetual production of hair cells and maturational changes in hair cell ultrastructure accompany postembryonic growth in an amphibian ear.

    OpenAIRE

    Corwin, J T

    1985-01-01

    Sensory hair cells are produced in the ears of birds and mammals only during early development, so that a programmed termination of hair cell proliferation leaves adult birds and mammals susceptible to irreversible deafness and balance disorders. This study reports that this is not an inherent feature of hair cells and is not shared through all the vertebrate classes. In toads (Bufo marinus) hair cells accumulate throughout life, increasing in the sacculus from approximately 400 cells at meta...

  10. Lhx2 Maintains Stem Cell Character in Hair Follicles

    OpenAIRE

    Rhee, Horace; Polak, Lisa; Fuchs, Elaine

    2006-01-01

    During embryogenesis, stem cells are set aside to fuel the postnatal hair cycle and repair the epidermis after injury. To define how hair follicle stem cells are specified and maintained in an undifferentiated state, we developed a strategy to isolate and transcriptionally profile embryonic hair progenitors in mice. We identified Lhx2 as a transcription factor positioned downstream of signals necessary to specify hair follicle stem cells, but upstream from signals required to drive activated ...

  11. Assessment and Preservation of Auditory Nerve Integrity in the Deafened Guinea Pig

    OpenAIRE

    Ramekers, D.

    2014-01-01

    Profound hearing loss is often caused by cochlear hair cell loss. Cochlear implants (CIs) essentially replace hair cells by encoding sound and conveying the signal by means of pulsatile electrical stimulation to the spiral ganglion cells (SGCs) which form the auditory nerve. SGCs progressively degenerate following hair cell loss, as a result of lost neurotrophic signaling from the hair cells. Degeneration of the auditory nerve may compromise the ability to hear with a CI. Therefore, the first...

  12. Developmental expression of BK channels in chick cochlear hair cells

    Directory of Open Access Journals (Sweden)

    Tong Mingjie

    2009-12-01

    Full Text Available Abstract Background Cochlear hair cells are high-frequency sensory receptors. At the onset of hearing, hair cells acquire fast, calcium-activated potassium (BK currents, turning immature spiking cells into functional receptors. In non-mammalian vertebrates, the number and kinetics of BK channels are varied systematically along the frequency-axis of the cochlea giving rise to an intrinsic electrical tuning mechanism. The processes that control the appearance and heterogeneity of hair cell BK currents remain unclear. Results Quantitative PCR results showed a non-monotonic increase in BK α subunit expression throughout embryonic development of the chick auditory organ (i.e. basilar papilla. Expression peaked near embryonic day (E 19 with six times the transcript level of E11 sensory epithelia. The steady increase in gene expression from E11 to E19 could not explain the sudden acquisition of currents at E18-19, implicating post-transcriptional mechanisms. Protein expression also preceded function but progressed in a sequence from diffuse cytoplasmic staining at early ages to punctate membrane-bound clusters at E18. Electrophysiology data confirmed a continued refinement of BK trafficking from E18 to E20, indicating a translocation of BK clusters from supranuclear to subnuclear domains over this critical developmental age. Conclusions Gene products encoding BK α subunits are detected up to 8 days before the acquisition of anti-BK clusters and functional BK currents. Therefore, post-transcriptional mechanisms seem to play a key role in the delayed emergence of calcium-sensitive currents. We suggest that regulation of translation and trafficking of functional α subunits, near voltage-gated calcium channels, leads to functional BK currents at the onset of hearing.

  13. Frequency locking in hair cells: Distinguishing between distinct resonant mechanisms

    CERN Document Server

    Edri, Yuval; Yochelis, Arik

    2016-01-01

    The auditory system displays remarkable mechanical sensitivity and frequency discrimination. These attributes have been shown to rely on an amplification process, which requires biochemical feedback loops. In some systems, the active process was shown to lead to spontaneous oscillations of hair cell bundles. In the last decade, models that display proximity to an oscillatory onset (a.k.a. Hopf bifurcation) have gained increasing support due to many advantages in explaining the hearing phenomenology. Particularly, they exhibit resonant responses to distinct frequencies of incoming sound waves. Unlike previous studies, two types of driving forces are being examined: additive, in which the external forcing term does not couple directly on the systems observable (passive coupling), and parametric, in which the forcing term directly affects the observable and thus intrinsically modifies the systems properties (active coupling). By applying universal principles near the Hopf bifurcation onset, we find several funda...

  14. Transcription factors in the development of inner ear hair cells.

    Science.gov (United States)

    Li, Shuna; Qian, Wei; Jiang, Guochang; Ma, Yongming

    2016-01-01

    Inner ear hair cells are the sensory receptors that detect and convert sound vibrations and head movements into neural signals. However, in humans, these cells are unable to regenerate if they are damaged or lost. Over thepast decade,there has been an exponential increase in interest and progress in understanding of the development of the inner ear and of hair cells, aiming to gain insights into hair cell repair or even regeneration. In hair cell development, various transcription factors have been found to be involved in the processes of hair cell proliferation, differentiation and survival. Among these transcription factors, Math1, Gata3, Sox2 and Atoh1 have been highlighted for their crucial role in the fate of hair cells. In this article, we will summarize the current understanding of the role of transcription factors in hair cell development, focusing on the role and possible mechanisms of Math1, Gata3, Sox2 and Atoh1. PMID:27100495

  15. FM dye photo-oxidation as a tool for monitoring membrane recycling in inner hair cells.

    OpenAIRE

    Dirk Kamin; Revelo, Natalia H.; Rizzoli, Silvio O.

    2014-01-01

    Styryl (FM) dyes have been used for more than two decades to investigate exo- and endocytosis in conventional synapses. However, they are difficult to use in the inner hair cells of the auditory pathway (IHCs), as FM dyes appear to penetrate through mechanotransducer channels into the cytosol of IHCs, masking endocytotic uptake. To solve this problem we applied to IHCs the FM dye photo-oxidation technique, which renders the dyes into electron microscopy markers. Photo-oxidation allowed the un...

  16. Efferent synapses return to inner hair cells in the aging cochlea

    OpenAIRE

    Lauer, Amanda M.; Fuchs, Paul; Ryugo, David K.; Francis, Howard W.

    2012-01-01

    Efferent innervation of the cochlea undergoes extensive modification early in development, but it is unclear if efferent synapses are modified by age, hearing loss, or both. Structural alterations in the cochlea affecting information transfer from the auditory periphery to the brain may contribute to age-related hearing deficits. We investigated changes to efferent innervation in the vicinity of inner hair cells (IHC) in young and old C57BL/6 mice using transmission electron microscopy to rev...

  17. Hair follicle dermal stem cells regenerate the dermal sheath, repopulate the dermal papilla, and modulate hair type.

    Science.gov (United States)

    Rahmani, Waleed; Abbasi, Sepideh; Hagner, Andrew; Raharjo, Eko; Kumar, Ranjan; Hotta, Akitsu; Magness, Scott; Metzger, Daniel; Biernaskie, Jeff

    2014-12-01

    The dermal papilla (DP) provide instructive signals required to activate epithelial progenitors and initiate hair follicle regeneration. DP cell numbers fluctuate over the hair cycle, and hair loss is associated with gradual depletion/atrophy of DP cells. How DP cell numbers are maintained in healthy follicles remains unclear. We performed in vivo fate mapping of adult hair follicle dermal sheath (DS) cells to determine their lineage relationship with DP and found that a subset of DS cells are retained following each hair cycle, exhibit self-renewal, and repopulate the DS and the DP with new cells. Ablating these hair follicle dermal stem cells and their progeny retarded hair regrowth and altered hair type specification, suggesting that they function to modulate normal DP function. This work identifies a bipotent stem cell within the adult hair follicle mesenchyme and has important implications toward restoration of hair growth after injury, disease, and aging. PMID:25465495

  18. Defining Hair Follicles in the Age of Stem Cell Bioengineering

    OpenAIRE

    Chuong, Cheng-Ming; Cotsarelis, George; Stenn, Kurt

    2007-01-01

    One challenge faced by stem cell biologists is the bioengineering of an organ. Ehama et al. (2007, this issue) used cells derived from human and rodent epidermis and dermal papilla to reconstitute hair-follicle mini-organs. Some result in hair follicles; others are hair follicle–like. The challenge calls for the development of a set of criteria to define a hair follicle so that bioengineered products in the future can be evaluated.

  19. LSD1 is Required for Hair Cell Regeneration in Zebrafish.

    Science.gov (United States)

    He, Yingzi; Tang, Dongmei; Cai, Chengfu; Chai, Renjie; Li, Huawei

    2016-05-01

    Lysine-specific demethylase 1 (LSD1/KDM1A) plays an important role in complex cellular processes such as differentiation, proliferation, apoptosis, and cell cycle progression. It has recently been demonstrated that during development, downregulation of LSD1 inhibits cell proliferation, modulates the expression of cell cycle regulators, and reduces hair cell formation in the zebrafish lateral line, which suggests that LSD1-mediated epigenetic regulation plays a key role in the development of hair cells. However, the role of LSD1 in hair cell regeneration after hair cell loss remains poorly understood. Here, we demonstrate the effect of LSD1 on hair cell regeneration following neomycin-induced hair cell loss. We show that the LSD1 inhibitor trans-2-phenylcyclopropylamine (2-PCPA) significantly decreases the regeneration of hair cells in zebrafish after neomycin damage. In addition, immunofluorescent staining demonstrates that 2-PCPA administration suppresses supporting cell proliferation and alters cell cycle progression. Finally, in situ hybridization shows that 2-PCPA significantly downregulates the expression of genes related to Wnt/β-catenin and Fgf activation. Altogether, our data suggest that downregulation of LSD1 significantly decreases hair cell regeneration after neomycin-induced hair cell loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus, LSD1 plays a critical role in hair cell regeneration and might represent a novel biomarker and potential therapeutic approach for the treatment of hearing loss. PMID:26008620

  20. Regional differences in lectin binding patterns of vestibular hair cells

    Science.gov (United States)

    Baird, Richard A.; Schuff, N. R.; Bancroft, J.

    1994-01-01

    Surface glycoconjugates of hair cells and supporting cells in the vestibular endorgans of the bullfrog were identified using biotinylated lectins with different carbohydrate specificities. Lectin binding in hair cells was consistent with the presence of glucose and mannose (CON A), galactose (RCA-I), N-acetylgalactosamine (VVA), but not fucose (UEA-I) residues. Hair cells in the bullfrog sacculus, unlike those in the utriculus and semicircular canals, did not stain for N-acetylglucosamine (WGA) or N-acetylgalactosamine (VVA). By contrast, WGA and, to a lesser extent, VVA, differentially stained utricular and semicircular canal hair cells, labeling hair cells located in peripheral, but not central, regions. In mammals, WGA uniformly labeled Type 1 hair cells while labeling, as in the bullfrog, Type 2 hair cells only in peripheral regions. These regional variations were retained after enzymatic digestion. We conclude that vestibular hair cells differ in their surface glycoconjugates and that differences in lectin binding patterns can be used to identify hair cell types and to infer the epithelial origin of isolated vestibular hair cells.

  1. Sensory hair cell death and regeneration in fishes

    Directory of Open Access Journals (Sweden)

    Gopinath Rajadinakaran

    2015-04-01

    Full Text Available Sensory hair cells are specialized mechanotransductive receptors required for hearing and vestibular function. Loss of hair cells in humans and other mammals is permanent and causes reduced hearing and balance. In the early 1980’s, it was shown that hair cells continue to be added to the inner ear sensory epithelia in cartilaginous and bony fishes. Soon thereafter, hair cell regeneration was documented in the chick cochlea following acoustic trauma. Since then, research using chick and other avian models has led to great insights into hair cell death and regeneration. However, with the rise of the zebrafish as a model organism for studying disease and developmental processes, there has been an increased interest in studying sensory hair cell death and regeneration in its lateral line and inner ears. Advances derived from studies in zebrafish and other fish species include understanding the effect of ototoxins on hair cells and finding otoprotectants to mitigate ototoxin damage, the role of cellular proliferation versus direct transdifferentiation during hair cell regeneration, and elucidating cellular pathways involved in the regeneration process. This review will summarize research on hair cell death and regeneration using fish models, indicate the potential strengths and weaknesses of these models, and discuss several emerging areas of future studies.

  2. Exploring the Role of Mechanotransduction Activation and Adaptation Kinetics in Hair Cell Filtering Using a Hodgkin-Huxley Approach

    Science.gov (United States)

    Wells, Gregg B.; Ricci, Anthony J.

    2011-11-01

    In the auditory system, mechanotransduction occurs in the hair cell sensory hair bundle and is the first major step in the translation of mechanical energy into electrical. Tonotopic variations in the activation kinetics of this process are posited to provide a low pass filter to the input. An adaptation process, also associated with mechanotransduction, is postulated to provide a high pass filter to the input in a tonotopic manner. Together a bandpass filter is created at the hair cell input. Corresponding mechanical components to both activation and adaptation are also suggested to be involved in generating cochlear amplification. A paradox to this story is that hair cells where the mechanotransduction properties are most robust possess an intrinsic electrical resonance mechanism proposed to account for all required tuning and amplification. A simple Hodgkin-Huxley type model is presented to attempt to determine the role of the activation and adaptation kinetics in further tuning hair cells that exhibit electrical resonance. Results further support that steady state mechanotransduction properties are critical for setting the resting potential of the hair cell while the kinetics of activation and adaptation are important for sharpening tuning around the characteristic frequency of the hair cell.

  3. Structure and function of the hair cell ribbon synapse.

    OpenAIRE

    Nouvian, R.; Beutner, D.; Parsons, T D; Moser, T.

    2006-01-01

    Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cel...

  4. Artificial Hair Cells for Sensing Flows

    Science.gov (United States)

    Chen, Jack

    2007-01-01

    The purpose of this article is to present additional information about the flow-velocity sensors described briefly in the immediately preceding article. As noted therein, these sensors can be characterized as artificial hair cells that implement an approximation of the sensory principle of flow-sensing cilia of fish: A cilium is bent by an amount proportional to the flow to which it is exposed. A nerve cell at the base of the cilium senses the flow by sensing the bending of the cilium. In an artificial hair cell, the artificial cilium is a microscopic cantilever beam, and the bending of an artificial cilium is measured by means of a strain gauge at its base (see Figure 1). Figure 2 presents cross sections of a representative sensor of this type at two different stages of its fabrication process. The process consists of relatively- low-temperature metallization, polymer-deposition, microfabrication, and surface-micromachining subprocesses, including plastic-deformation magnetic assembly (PDMA), which is described below. These subprocesses are suitable for a variety of substrate materials, including silicon, some glasses, and some polymers. Moreover, because it incorporates a polymeric supporting structure, this sensor is more robust, relative to its silicon-based counterparts.

  5. TMC function in hair cell transduction.

    Science.gov (United States)

    Holt, Jeffrey R; Pan, Bifeng; Koussa, Mounir A; Asai, Yukako

    2014-05-01

    Transmembrane channel-like (TMC) proteins 1 and 2 are necessary for hair cell mechanotransduction but their precise function is controversial. A growing body of evidence supports a direct role for TMC1 and TMC2 as components of the transduction complex. However, a number of important questions remain and alternate hypotheses have been proposed. Here we present an historical overview of the identification and cloning of Tmc genes, a discussion of mutations in TMC1 that cause deafness in mice and humans and a brief review of other members of the Tmc gene superfamily. We also examine expression of Tmc mRNAs and localization of the protein products. The review focuses on potential functions of TMC proteins and the evidence from Beethoven mice that suggests a direct role for TMC1 in hair cell mechanotransduction. Data that support alternate interpretations are also considered. The article concludes with a discussion of outstanding questions and future directions for TMC research. This article is part of a Special Issue entitled . PMID:24423408

  6. Acoustic trauma increases cochlear and hair cell uptake of gentamicin.

    Directory of Open Access Journals (Sweden)

    Hongzhe Li

    Full Text Available BACKGROUND: Exposure to intense sound or high doses of aminoglycoside antibiotics can increase hearing thresholds, induce cochlear dysfunction, disrupt hair cell morphology and promote hair cell death, leading to permanent hearing loss. When the two insults are combined, synergistic ototoxicity occurs, exacerbating cochlear vulnerability to sound exposure. The underlying mechanism of this synergism remains unknown. In this study, we tested the hypothesis that sound exposure enhances the intra-cochlear trafficking of aminoglycosides, such as gentamicin, leading to increased hair cell uptake of aminoglycosides and subsequent ototoxicity. METHODS: Juvenile C57Bl/6 mice were exposed to moderate or intense sound levels, while fluorescently-conjugated or native gentamicin was administered concurrently or following sound exposure. Drug uptake was then examined in cochlear tissues by confocal microscopy. RESULTS: Prolonged sound exposure that induced temporary threshold shifts increased gentamicin uptake by cochlear hair cells, and increased gentamicin permeation across the strial blood-labyrinth barrier. Enhanced intra-cochlear trafficking and hair cell uptake of gentamicin also occurred when prolonged sound, and subsequent aminoglycoside exposure were temporally separated, confirming previous observations. Acute, concurrent sound exposure did not increase cochlear uptake of aminoglycosides. CONCLUSIONS: Prolonged, moderate sound exposures enhanced intra-cochlear aminoglycoside trafficking into the stria vascularis and hair cells. Changes in strial and/or hair cell physiology and integrity due to acoustic overstimulation could increase hair cell uptake of gentamicin, and may represent one mechanism of synergistic ototoxicity.

  7. Outer Hair Cell Somatic Electromotility In Vivo and Power Transfer to the Organ of Corti

    OpenAIRE

    Ramamoorthy, Sripriya; Nuttall, Alfred L.

    2012-01-01

    The active amplification of sound-induced vibrations in the cochlea, known to be crucial for auditory sensitivity and frequency selectivity, is not well understood. The outer hair cell (OHC) somatic electromotility is a potential mechanism for such amplification. Its effectiveness in vivo is putatively limited by the electrical low-pass filtering of the cell's transmembrane potential. However, the transmembrane potential is an incomplete metric. We propose and estimate two metrics to evaluate...

  8. Investigating Outer Hair Cell Motility with a Combination of External Alternating Electrical Field Stimulation and High-speed Image Analysis

    OpenAIRE

    Kitani, Rei; Kalinec, Federico

    2011-01-01

    OHCs are cylindrical sensorimotor cells located in the Organ of Corti, the auditory organ inside the mammalian inner ear. The name "hair cells" derives from their characteristic apical bundle of stereocilia, a critical element for detection and transduction of sound energy 1. OHCs are able to change shape —elongate, shorten and bend— in response to electrical, mechanical and chemical stimulation, a motor response considered crucial for cochlear amplification of acoustic signals 2.

  9. Photometric recording of transmembrane potential in outer hair cells

    Science.gov (United States)

    Nakagawa, Takashi; Oghalai, John S.; Saggau, Peter; Rabbitt, Richard D.; Brownell, William E.

    2006-06-01

    Cochlear outer hair cells (OHCs) are polarized epithelial cells that have mechanoelectrical transduction channels within their apical stereocilia and produce electromotile force along their lateral wall. Phase shifts, or time delays, in the transmembrane voltage occurring at different axial locations along the cell may contribute to our understanding of how these cells operate at auditory frequencies. We developed a method to optically measure the phase of the OHC transmembrane potential using the voltage-sensitive dye (VSD) di-8-ANEPPS. The exit aperture of a fibre-optic light source was driven in two dimensions so that a 24 µm spot of excitation light could be positioned along the length of the OHC. We used the whole-cell patch-clamp technique in the current-clamp mode to stimulate the OHC at the base. The photometric response and the voltage response were monitored with a photodetector and patch-clamp amplifier, respectively. The photometric response was used to measure the regional changes in the membrane potential in response to maintained (dc) and sinusoidal (ac) current stimuli applied at the base of the cell. We used a neutral density filter to lower the excitation light intensity and reduce phototoxicity. A sensitive detector and lock-in amplifier were used to measure the small ac VSD signal. This permitted measurements of the ac photometric response below the noise floor of the static fluorescence. The amplitude and phase components of the photometric response were recorded for stimuli up to 800 Hz. VSD data at 400-800 Hz show the presence of a small phase delay between the stimulus voltage at the base of the cell and the local membrane potential measured along the lateral wall. Results are consistent with the hypothesis that OHCs exhibit inhomogeneous membrane potentials that vary with position in analogy with the voltage in nerve axons.

  10. Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

    Science.gov (United States)

    Baird, R. A.; Burton, M. D.; Fashena, D. S.; Naeger, R. A.

    2000-01-01

    Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate of damaged hair cells and the origin of immature hair cells after gentamicin treatment in mitotically blocked cultures of the bullfrog saccule. Extruding and fragmenting hair cells, which undergo apoptotic cell death, are replaced by scar formations. After losing their bundles, sublethally damaged hair cells remain in the sensory epithelium for prolonged periods, acquiring supporting cell-like morphology and immunoreactivity. These modes of damage appear to be mutually exclusive, implying that sublethally damaged hair cells repair their bundles. Transitional cells, coexpressing hair cell and supporting cell markers, are seen near scar formations created by the expansion of neighboring supporting cells. Most of these cells have morphology and immunoreactivity similar to that of sublethally damaged hair cells. Ultrastructural analysis also reveals that most immature hair cells had autophagic vacuoles, implying that they originated from damaged hair cells rather than supporting cells. Some transitional cells are supporting cells participating in scar formations. Supporting cells also decrease in number during hair cell recovery, supporting the conclusion that some supporting cells undergo phenotypic conversion into hair cells without an intervening mitotic event.

  11. Fate of Mammalian Cochlear Hair Cells and Stereocilia after Loss of the Stereocilia

    OpenAIRE

    Jia, Shuping; Yang, Shiming; Guo, Weiwei; David Z Z He

    2009-01-01

    Cochlear hair cells transduce mechanical stimuli into electrical activity. The site of hair cell transduction is the hair bundle, an array of stereocilia with different height arranged in a staircase. Tip links connect the apex of each stereocilium to the side of its taller neighbor. The hair bundle and tip links of hair cells are susceptible to acoustic trauma and ototoxic drugs. It has been shown that hair cells in lower vertebrates and in the mammalian vestibular system may survive bundle ...

  12. The Genetics of Hair Cell Development and Regeneration

    OpenAIRE

    Groves, Andrew K.; Zhang, Kaidi D.; Fekete, Donna M.

    2013-01-01

    Sensory hair cells are exquisitely sensitive vertebrate mechanoreceptors that mediate the senses of hearing and balance. Understanding the factors that regulate the development of these cells is important, not only for our understanding of ear development and its functional physiology, but also to shed light on how these cells may be replaced therapeutically. In this review, we describe the signals and molecular mechanisms that initiate hair cell development in vertebrates, with particular em...

  13. Gab1 and Mapk Signaling Are Essential in the Hair Cycle and Hair Follicle Stem Cell Quiescence

    OpenAIRE

    Özlem Akilli Öztürk; Hubert Pakula; Jolanta Chmielowiec; Jingjing Qi; Simone Stein; Linxiang Lan; Yoshiteru Sasaki; Klaus Rajewsky; Walter Birchmeier

    2015-01-01

    Gab1 is a scaffold protein that acts downstream of receptor tyrosine kinases. Here, we produced conditional Gab1 mutant mice (by K14- and Krox20-cre) and show that Gab1 mediates crucial signals in the control of both the hair cycle and the self-renewal of hair follicle stem cells. Remarkably, mutant hair follicles do not enter catagen, the destructive phase of the hair cycle. Instead, hair follicle stem cells lose quiescence and become exhausted, and thus no stem cell niches are established i...

  14. Pattern of hair cell loss and delayed peripheral neuron degeneration in inner ear by a high-dose intratympanic gentamicin

    Institute of Scientific and Technical Information of China (English)

    Jintao Yu; Dalian Ding; Fengjun Wang; Haiyan Jiang; Hong Sun; Richard Salvi

    2014-01-01

    To gain insights into the ototoxic effects of aminoglycoside antibiotics (AmAn) and delayed peripheral ganglion neuron death in the inner ear, experimental animal models were widely used with several different approaches including AmAn systemic injections, combination treat-ment of AmAn and diuretics, or local application of AmAn. In these approaches, systemic AmAn treatment alone usually causes incomplete damage to hair cells in the inner ear. Co-administration of diuretic and AmAn can completely destroy the cochlear hair cells, but it is impossible to damage the vestibular system. Only the approach of AmAn local application can selectively eliminate most sensory hair cells in the inner ear. Therefore, AmAn local application is more suitable for studies for complete hair cell destructions in cochlear and vestibular system and the following delayed peripheral ganglion neuron death. In current studies, guinea pigs were unilaterally treated with a high concentration of gentamicin (GM, 40 mg/ml) through the tympanic membrane into the middle ear cavity. Auditory functions and vestibular functions were measured before and after GM treatment. The loss of hair cells and delayed degeneration of ganglion neurons in both cochlear and vestibular system were quantified 30 days or 60 days after treatment. The results showed that both auditory and vestibular functions were completely abolished after GM treatment. The sensory hair cells were totally missing in the cochlea, and severely destroyed in vestibular end-organs. The delayed spiral ganglion neuron death 60 days after the deafening procedure was over 50%. However, no obvious pathological changes were observed in vestibular ganglion neurons 60 days post-treatment. These results indicated that a high concentration of gentamycin delivered to the middle ear cavity can destroy most sensory hair cells in the inner ear that subsequently causes the delayed spiral ganglion neuron degeneration. This model might be useful for studies

  15. A search for factors specifying tonotopy implicates DNER in hair-cell development in the chick’s cochlea

    OpenAIRE

    Kowalik, Lukasz; Hudspeth, A. J.

    2011-01-01

    The accurate perception of sound frequency by vertebrates relies upon the tuning of hair cells, which are arranged along auditory organs according to frequency. This arrangement, which is termed a tonotopic gradient, results from the coordination of many cellular and extracellular features. Seeking the mechanisms that orchestrate those features and govern the tonotopic gradient, we used expression microarrays to identify genes differentially expressed between the high- and low-frequency cochl...

  16. Outer hair cell piezoelectricity: Frequency response enhancement and resonance behavior

    Science.gov (United States)

    Weitzel, Erik K.; Tasker, Ron; Brownell, William E.

    2003-09-01

    Stretching or compressing an outer hair cell alters its membrane potential and, conversely, changing the electrical potential alters its length. This bi-directional energy conversion takes place in the cell's lateral wall and resembles the direct and converse piezoelectric effects both qualitatively and quantitatively. A piezoelectric model of the lateral wall has been developed that is based on the electrical and material parameters of the lateral wall. An equivalent circuit for the outer hair cell that includes piezoelectricity shows a greater admittance at high frequencies than one containing only membrane resistance and capacitance. The model also predicts resonance at ultrasonic frequencies that is inversely proportional to cell length. These features suggest all mammals use outer hair cell piezoelectricity to support the high-frequency receptor potentials that drive electromotility. It is also possible that members of some mammalian orders use outer hair cell piezoelectric resonance in detecting species-specific vocalizations.

  17. Hair regeneration using adipose-derived stem cells.

    Science.gov (United States)

    Jin, Su-Eon; Sung, Jong-Hyuk

    2016-03-01

    Adipose-derived stem cells (ASCs) have been used in tissue repair and regeneration. Recently, it was reported that ASC transplantation promotes hair growth in animal experiments, and a conditioned medium of ASCs (ASC-CM) induced the proliferation of hair-compositing cells in vitro. However, ASCs and their conditioned medium have shown limited effectiveness in clinical settings. ASC preconditioning is one strategy that can be used to enhance the efficacy of ASCs and ASC-CM. Therefore, we highlighted the functional role of ASCs in hair cycle progression and also the advantages and disadvantages of their application in hair regeneration. In addition, we introduced novel ASC preconditioning methods to enhance hair regeneration using ASC stimulators, such as vitamin C, platelet-derived growth factor, hypoxia, and ultraviolet B. PMID:26536569

  18. The calcium-activated potassium channels of turtle hair cells

    OpenAIRE

    1995-01-01

    A major factor determining the electrical resonant frequency of turtle cochlear hair cells is the time course of the Ca-activated K current (Art, J. J., and R. Fettiplace. 1987. Journal of Physiology. 385:207- 242). We have examined the notion that this time course is dictated by the K channel kinetics by recording single Ca-activated K channels in inside-out patches from isolated cells. A hair cell's resonant frequency was estimated from its known correlation with the dimensions of the hair ...

  19. Auxin transport through non-hair cells sustains root-hair development

    OpenAIRE

    Jones, Angharad R.; Kramer, Eric M.; Knox, Kirsten; Swarup, Ranjan; Bennett, Malcolm J; Lazarus, Colin M.; Leyser, H. M. Ottoline; Grierson, Claire S.

    2008-01-01

    The plant hormone auxin controls root epidermal cell development in a concentration-dependent manner 1-3. Root hairs are produced on a subset of epidermal cells as they increase in distance from the root tip. Auxin is required for their initiation 4-7 and continued growth 8-11, but little is known about its distribution in this region of the root. Counter to the expectation that hair cells might require active auxin influx to ensure auxin supply, we did not detect the auxin-influx transporter...

  20. Control of hair cell excitability by vestibular primary sensory neurons.

    OpenAIRE

    Brugeaud, Aurore; Travo, Cécile; Demêmes, Danielle; Lenoir, Marc; Llorens, Jordi; Puel, Jean-Luc; Chabbert, Christian

    2007-01-01

    In the rat utricle, synaptic contacts between hair cells and the nerve fibers arising from the vestibular primary neurons form during the first week after birth. During that period, the sodium-based excitability that characterizes neonate utricle sensory cells is switched off. To investigate whether the establishment of synaptic contacts was responsible for the modulation of the hair cell excitability, we used an organotypic culture of rat utricle in which the setting of synapses was prevente...

  1. Induction of Functional Hair-Cell-Like Cells from Mouse Cochlear Multipotent Cells

    OpenAIRE

    Quanwen Liu; Yi Shen; Jiarong Chen; Jie Ding; Zihua Tang; Cui Zhang; Jianling Chen; Liang Li; Ping Chen; Jinfu Wang

    2016-01-01

    In this paper, we developed a two-step-induction method of generating functional hair cells from inner ear multipotent cells. Multipotent cells from the inner ear were established and induced initially into progenitor cells committed to the inner ear cell lineage on the poly-L-lysine substratum. Subsequently, the committed progenitor cells were cultured on the mitotically inactivated chicken utricle stromal cells and induced into hair-cell-like cells containing characteristic stereocilia bund...

  2. Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus.

    Science.gov (United States)

    Kurioka, Takaomi; Lee, Min Young; Heeringa, Amarins N; Beyer, Lisa A; Swiderski, Donald L; Kanicki, Ariane C; Kabara, Lisa L; Dolan, David F; Shore, Susan E; Raphael, Yehoash

    2016-09-22

    In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus (CN). However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT-induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and CN neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination. PMID:27403879

  3. Regeneration of the auditory nerve - a cell transplantation study

    OpenAIRE

    Palmgren, Björn

    2011-01-01

    Since in mammals, the hair cells or the spiral ganglion neurons (SGNs) in the inner ear do not regenerate, damage to these cells is an irreversible process. Presently the only aid for patients with severe to profound hearing impairment due to damaged hair cells is a cochlear implant (CI). A CI converts sound to electrical signals that stimulate the SGNs via an electrode that is implanted into the cochlea. Hence, for a successful outcome the CI is dependant on the activation ...

  4. Effect of low-level laser treatment on cochlea hair-cell recovery after ototoxic hearing loss

    Science.gov (United States)

    Rhee, Chung-Ku; He, Peijie; Jung, Jae Yun; Ahn, Jin-Chul; Chung, Phil-Sang; Lee, Min Young; Suh, Myung-Whan

    2013-12-01

    The primary cause of hearing loss includes damage to cochlear hair cells. Low-level laser therapy (LLLT) has become a popular treatment for damaged nervous systems. Based on the idea that cochlea hair cells and neural cells are from same developmental origin, the effect of LLLT on hearing loss in animal models is evaluated. Hearing loss animal models were established, and the animals were irradiated by 830-nm diode laser once a day for 10 days. Power density of the laser treatment was 900 mW/cm2, and the fluence was 162 to 194 J. The tympanic membrane was evaluated after LLLT. Thresholds of auditory brainstem responses were evaluated before treatment, after gentamicin, and after 10 days of LLLT. Quantitative scanning electron microscopic (SEM) observations were done by counting remaining hair cells. Tympanic membranes were intact at the end of the experiment. No adverse tissue reaction was found. On SEM images, LLLT significantly increased the number of hair cells in middle and basal turns. Hearing was significantly improved by laser irradiation. After LLLT treatment, both the hearing threshold and hair-cell count significantly improved.

  5. Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

    OpenAIRE

    Jiang, Linjia; Romero-Carvajal, Andres; Haug, Jeff S.; Seidel, Christopher W.; Piotrowski, Tatjana

    2014-01-01

    Deafness is caused largely by the death of sensory hair cells in the inner ear. In contrast to nonmammalian vertebrates, human hair cells do not regenerate. Understanding the mechanisms that regulate hair cell regeneration in zebrafish may shed light on the factors that prevent hair cell regeneration in mammals. RNA-Seq analysis of regenerating sensory organs uncovered dynamic changes in the expression of signaling pathways during zebrafish hair cell regeneration. Unexpectedly, the Wnt/β-cate...

  6. Acoustic Trauma Increases Cochlear and Hair Cell Uptake of Gentamicin

    OpenAIRE

    Hongzhe Li; Qi Wang; Steyger, Peter S.

    2011-01-01

    BACKGROUND: Exposure to intense sound or high doses of aminoglycoside antibiotics can increase hearing thresholds, induce cochlear dysfunction, disrupt hair cell morphology and promote hair cell death, leading to permanent hearing loss. When the two insults are combined, synergistic ototoxicity occurs, exacerbating cochlear vulnerability to sound exposure. The underlying mechanism of this synergism remains unknown. In this study, we tested the hypothesis that sound exposure enhances the intra...

  7. Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells

    Science.gov (United States)

    Muller, Mees; Heeck, Kier

    2016-01-01

    Vertebrate semicircular canals (SCC) first appeared in the vertebrates (i.e. ancestral fish) over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm), 10 times more compliant to bending (44 vs. 500 nN/m), and have a 100-fold higher tip displacement threshold (level of the mechanoreceptors of the SCC. PMID:27448330

  8. Alternative Splice Forms Influence Functions of Whirlin in Mechanosensory Hair Cell Stereocilia.

    Science.gov (United States)

    Ebrahim, Seham; Ingham, Neil J; Lewis, Morag A; Rogers, Michael J C; Cui, Runjia; Kachar, Bechara; Pass, Johanna C; Steel, Karen P

    2016-05-01

    WHRN (DFNB31) mutations cause diverse hearing disorders: profound deafness (DFNB31) or variable hearing loss in Usher syndrome type II. The known role of WHRN in stereocilia elongation does not explain these different pathophysiologies. Using spontaneous and targeted Whrn mutants, we show that the major long (WHRN-L) and short (WHRN-S) isoforms of WHRN have distinct localizations within stereocilia and also across hair cell types. Lack of both isoforms causes abnormally short stereocilia and profound deafness and vestibular dysfunction. WHRN-S expression, however, is sufficient to maintain stereocilia bundle morphology and function in a subset of hair cells, resulting in some auditory response and no overt vestibular dysfunction. WHRN-S interacts with EPS8, and both are required at stereocilia tips for normal length regulation. WHRN-L localizes midway along the shorter stereocilia, at the level of inter-stereociliary links. We propose that differential isoform expression underlies the variable auditory and vestibular phenotypes associated with WHRN mutations. PMID:27117407

  9. Alternative Splice Forms Influence Functions of Whirlin in Mechanosensory Hair Cell Stereocilia

    Directory of Open Access Journals (Sweden)

    Seham Ebrahim

    2016-05-01

    Full Text Available WHRN (DFNB31 mutations cause diverse hearing disorders: profound deafness (DFNB31 or variable hearing loss in Usher syndrome type II. The known role of WHRN in stereocilia elongation does not explain these different pathophysiologies. Using spontaneous and targeted Whrn mutants, we show that the major long (WHRN-L and short (WHRN-S isoforms of WHRN have distinct localizations within stereocilia and also across hair cell types. Lack of both isoforms causes abnormally short stereocilia and profound deafness and vestibular dysfunction. WHRN-S expression, however, is sufficient to maintain stereocilia bundle morphology and function in a subset of hair cells, resulting in some auditory response and no overt vestibular dysfunction. WHRN-S interacts with EPS8, and both are required at stereocilia tips for normal length regulation. WHRN-L localizes midway along the shorter stereocilia, at the level of inter-stereociliary links. We propose that differential isoform expression underlies the variable auditory and vestibular phenotypes associated with WHRN mutations.

  10. Hair & skin derived progenitor cells: In search of a candidate cell for regenerative medicine

    OpenAIRE

    Anil Kumar; Sujata Mohanty; Sushmita Bose Nandy; Somesh Gupta; Binod K Khaitan; Shilpa Sharma; Balram Bhargava; Balram Airan

    2016-01-01

    Background & objectives: Skin is an established tissue source for cell based therapy. The hair follicle has been introduced later as a tissue source for cell based therapy. The ease of tissue harvest and multipotent nature of the resident stem cells in skin and hair follicle has promoted basic and clinical research in this area. This study was conducted to evaluate skin stem cells (SSCs) and hair follicle stem cells (HFSCs) as candidate cells appropriate for neuronal and melanocyte lineage di...

  11. Amplitude death of coupled hair bundles with stochastic channel noise

    CERN Document Server

    Kim, Kyung-Joong

    2014-01-01

    Hair cells conduct auditory transduction in vertebrates. In lower vertebrates such as frogs and turtles, due to the active mechanism in hair cells, hair bundles(stereocilia) can be spontaneously oscillating or quiescent. Recently, the amplitude death phenomenon has been proposed [K.-H. Ahn, J. R. Soc. Interface, {\\bf 10}, 20130525 (2013)] as a mechanism for auditory transduction in frog hair-cell bundles, where sudden cessation of the oscillations arises due to the coupling between non-identical hair bundles. The gating of the ion channel is intrinsically stochastic due to the stochastic nature of the configuration change of the channel. The strength of the noise due to the channel gating can be comparable to the thermal Brownian noise of hair bundles. Thus, we perform stochastic simulations of the elastically coupled hair bundles. In spite of stray noisy fluctuations due to its stochastic dynamics, our simulation shows the transition from collective oscillation to amplitude death as inter-bundle coupling str...

  12. Proliferation of Functional Hair Cells in Vivo in the Absence of the Retinoblastoma Protein

    Science.gov (United States)

    Sage, Cyrille; Huang, Mingqian; Karimi, Kambiz; Gutierrez, Gabriel; Vollrath, Melissa A.; Zhang, Duan-Sun; García-Añoveros, Jaime; Hinds, Philip W.; Corwin, Jeffrey T.; Corey, David P.; Chen, Zheng-Yi

    2005-02-01

    In mammals, hair cell loss causes irreversible hearing and balance impairment because hair cells are terminally differentiated and do not regenerate spontaneously. By profiling gene expression in developing mouse vestibular organs, we identified the retinoblastoma protein (pRb) as a candidate regulator of cell cycle exit in hair cells. Differentiated and functional mouse hair cells with a targeted deletion of Rb1 undergo mitosis, divide, and cycle, yet continue to become highly differentiated and functional. Moreover, acute loss of Rb1 in postnatal hair cells caused cell cycle reentry. Manipulation of the pRb pathway may ultimately lead to mammalian hair cell regeneration.

  13. Directional cell migration, but not proliferation, drives hair placode morphogenesis.

    Science.gov (United States)

    Ahtiainen, Laura; Lefebvre, Sylvie; Lindfors, Päivi H; Renvoisé, Elodie; Shirokova, Vera; Vartiainen, Maria K; Thesleff, Irma; Mikkola, Marja L

    2014-03-10

    Epithelial reorganization involves coordinated changes in cell shapes and movements. This restructuring occurs during formation of placodes, ectodermal thickenings that initiate the morphogenesis of epithelial organs including hair, mammary gland, and tooth. Signaling pathways in ectodermal placode formation are well known, but the cellular mechanisms have remained ill defined. We established imaging methodology for live visualization of embryonic skin explants during the first wave of hair placode formation. We found that the vast majority of placodal cells were nonproliferative throughout morphogenesis. We show that cell compaction and centripetal migration are the main cellular mechanisms associated with hair placode morphogenesis and that inhibition of actin remodeling suppresses placode formation. Stimulation of both ectodysplasin/NF-κB and Wnt/β-catenin signaling increased cell motility and the number of cells committed to placodal fate. Thus, cell fate choices and morphogenetic events are controlled by the same molecular pathways, providing the framework for coordination of these two processes. PMID:24636260

  14. Auditory and non-auditory effects of noise on health

    OpenAIRE

    Basner, Mathias; Babisch, Wolfgang; Davis, Adrian; Brink, Mark; Clark, Charlotte; Janssen, Sabine; Stansfeld, Stephen

    2013-01-01

    Noise is pervasive in everyday life and can cause both auditory and non-auditory health effects. Noise-induced hearing loss remains highly prevalent in occupational settings, and is increasingly caused by social noise exposure (eg, through personal music players). Our understanding of molecular mechanisms involved in noise-induced hair-cell and nerve damage has substantially increased, and preventive and therapeutic drugs will probably become available within 10 years. Evidence of the non-aud...

  15. Spontaneous regeneration of cochlear supporting cells after neonatal ablation ensures hearing in the adult mouse

    OpenAIRE

    Mellado Lagarde, Marcia M.; Wan, Guoqiang; Zhang, LingLi; Gigliello, Angelica R; McInnis, John J.; Zhang, Yingxin; Bergles, Dwight; Zuo, Jian; Corfas, Gabriel

    2014-01-01

    The auditory sensory epithelium contains two major cell types: hair cells and supporting cells. Mammalian auditory hair cells do not regenerate after damage or loss, resulting in permanent hearing impairment. How supporting cell loss affects auditory function remains to be determined. Here, we demonstrate that inner border and inner phalangeal cells, the two types of supporting cells surrounding inner hair cells, can be replenished completely after selective ablation in the neonatal cochlea, ...

  16. Hair cell recovery in mitotically blocked cultures of the bullfrog saccule

    OpenAIRE

    Baird, Richard A.; Burton, Miriam D.; Fashena, David S.; Naeger, Rebecca A.

    2000-01-01

    Hair cells in many nonmammalian vertebrates are regenerated by the mitotic division of supporting cell progenitors and the differentiation of the resulting progeny into new hair cells and supporting cells. Recent studies have shown that nonmitotic hair cell recovery after aminoglycoside-induced damage can also occur in the vestibular organs. Using hair cell and supporting cell immunocytochemical markers, we have used confocal and electron microscopy to examine the fate...

  17. Molecular anatomy and physiology of exocytosis in sensory hair cells.

    Science.gov (United States)

    Rutherford, Mark A; Pangršič, Tina

    2012-01-01

    Hair cells mediate our senses of hearing and balance by synaptic release of glutamate from somatic active zones (AZs). They share conserved mechanisms of exocytosis with neurons and other secretory cells of diverse form and function. Concurrently, AZs of these neuro-epithelial hair cells employ several processes that differ remarkably from those of neuronal synaptic terminals of the brain. Their unique molecular anatomy enables them to better respond to small, graded changes in membrane potential and to produce unsurpassed rates of exocytosis. Here, we focus on the AZs of cochlear inner hair cells (IHCs). As in other hair cells, these AZs are occupied by a cytoplasmic extension of the presynaptic density, called the synaptic ribbon: a specialized protein complex required for normal physiological function. Some proteins found at IHC synapses are uniquely expressed or enriched there, where their disruption can beget deafness in humans and in animal models. Other proteins, essential for regulation of conventional neuronal Ca(2+)-triggered fusion, are apparently absent from IHCs. Certain common synaptic proteins appear to have extra significance at ribbon-type AZs because of their interactions with unique molecules, their unusual concentrations, or their atypical localization and regulation. We summarize the molecular-anatomical specializations that underlie the unique synaptic physiology of hair cells. PMID:22682011

  18. Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

    Science.gov (United States)

    Tang, Yan; Luo, Binping; Deng, Zhili; Wang, Ben; Liu, Fangfen; Li, Jinmao; Shi, Wei; Xie, Hongfu; Hu, Xingwang

    2016-01-01

    Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect hair regeneration has not been elaborated upon. Methods. We compared the difference in mitochondrial morphology and activity between telogen bulge cells and anagen matrix cells. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured to evaluate redox balance. In addition, the level of pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were estimated to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking. Results. During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively stable ROS levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration switched from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking repressed hair regeneration in vivo. Conclusions. Upon HFSCs differentiation, mitochondria are elongated with more abundant cristae and show higher activity, accompanying with activated aerobic respiration in differentiated cells for higher energy supply. Also, dysfunction of mitochondrial respiration delays hair

  19. The auditory organ: active amplifier and highly sensitive measuring system

    International Nuclear Information System (INIS)

    The present paper provides a brief review on topical issues of auditory physiology. Recent data on transduction mechanism and adaptation in hair cells as well as on the possible role of outer hair cells in amplifying basilar membrane motion are presented. Strategies of present physiological research in dealing with sensorineural deafness are discussed. (orig.)

  20. Derivation of hair-inducing cell from human pluripotent stem cells.

    Science.gov (United States)

    Gnedeva, Ksenia; Vorotelyak, Ekaterina; Cimadamore, Flavio; Cattarossi, Giulio; Giusto, Elena; Terskikh, Vasiliy V; Terskikh, Alexey V

    2015-01-01

    Dermal Papillae (DP) is a unique population of mesenchymal cells that was shown to regulate hair follicle formation and growth cycle. During development most DP cells are derived from mesoderm, however, functionally equivalent DP cells of cephalic hairs originate from Neural Crest (NC). Here we directed human embryonic stem cells (hESCs) to generate first NC cells and then hair-inducing DP-like cells in culture. We showed that hESC-derived DP-like cells (hESC-DPs) express markers typically found in adult human DP cells (e.g., p-75, nestin, versican, SMA, alkaline phosphatase) and are able to induce hair follicle formation when transplanted under the skin of immunodeficient NUDE mice. Engineered to express GFP, hESC-derived DP-like cells incorporate into DP of newly formed hair follicles and express appropriate markers. We demonstrated that BMP signaling is critical for hESC-DP derivation since BMP inhibitor dorsomorphin completely eliminated hair-inducing activity from hESC-DP cultures. DP cells were proposed as the cell-based treatment for hair loss diseases. Unfortunately human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly loose their ability to induce hair follicle formation when cultured. In this context derivation of functional hESC-DP cells capable of inducing a robust hair growth for the first time shown here can become an important finding for the biomedical science. PMID:25607935

  1. Derivation of hair-inducing cell from human pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Ksenia Gnedeva

    Full Text Available Dermal Papillae (DP is a unique population of mesenchymal cells that was shown to regulate hair follicle formation and growth cycle. During development most DP cells are derived from mesoderm, however, functionally equivalent DP cells of cephalic hairs originate from Neural Crest (NC. Here we directed human embryonic stem cells (hESCs to generate first NC cells and then hair-inducing DP-like cells in culture. We showed that hESC-derived DP-like cells (hESC-DPs express markers typically found in adult human DP cells (e.g., p-75, nestin, versican, SMA, alkaline phosphatase and are able to induce hair follicle formation when transplanted under the skin of immunodeficient NUDE mice. Engineered to express GFP, hESC-derived DP-like cells incorporate into DP of newly formed hair follicles and express appropriate markers. We demonstrated that BMP signaling is critical for hESC-DP derivation since BMP inhibitor dorsomorphin completely eliminated hair-inducing activity from hESC-DP cultures. DP cells were proposed as the cell-based treatment for hair loss diseases. Unfortunately human DP cells are not suitable for this purpose because they cannot be obtained in necessary amounts and rapidly loose their ability to induce hair follicle formation when cultured. In this context derivation of functional hESC-DP cells capable of inducing a robust hair growth for the first time shown here can become an important finding for the biomedical science.

  2. Identification of the Hair Cell Soma-1 Antigen, HCS-1, as Otoferlin

    OpenAIRE

    Goodyear, Richard J.; Legan, P. Kevin; Christiansen, Jeffrey R.; Xia, Bei; Korchagina, Julia; Gale, Jonathan E.; Mark E Warchol; Corwin, Jeffrey T.; Richardson, Guy P.

    2010-01-01

    Hair cells, the mechanosensitive receptor cells of the inner ear, are critical for our senses of hearing and balance. The small number of these receptor cells in the inner ear has impeded the identification and characterization of proteins important for hair cell function. The binding specificity of monoclonal antibodies provides a means for identifying hair cell-specific proteins and isolating them for further study. We have generated a monoclonal antibody, termed hair cell soma-1 (HCS-1), w...

  3. Intra- and extracellular calcium modulates stereocilia stiffness on chick cochlear hair cells.

    OpenAIRE

    Pae, S S; Saunders, J. C.

    1994-01-01

    Segments of the chick basilar papilla were isolated and maintained in culture medium. The sensory hair bundle of individual hair cells was observed with light microscopy and stimulated with a water microjet at 600 Hz. Hair bundle motion was slowed by illuminating the microscope with stroboscopic light, and water jet intensity was systematically varied in decibel (dB) steps until a visual detection level (VDL) threshold of hair bundle motion was achieved. The VDL threshold of many hair cells w...

  4. Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

    OpenAIRE

    Tang, Yan; Luo, Binping; Deng, Zhili; Wang, Ben; Liu, Fangfen; Li, Jinmao; SHI, Wei; Xie, Hongfu; Hu, Xingwang; Li, Ji

    2016-01-01

    Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect ...

  5. Direct effects of music in non-auditory cells in culture

    Directory of Open Access Journals (Sweden)

    Nathalia dos Reis Lestard

    2013-01-01

    Full Text Available The biological effects of electromagnetic waves are widely studied, especially due to their harmful effects, such as radiation-induced cancer and to their application in diagnosis and therapy. However, the biological effects of sound, another physical agent to which we are frequently exposed have been considerably disregarded by the scientific community. Although a number of studies suggest that emotions evoked by music may be useful in medical care, alleviating stress and nociception in patients undergoing surgical procedures as well as in cancer and burned patients, little is known about the mechanisms by which these effects occur. It is generally accepted that the mechanosensory hair cells in the ear transduce the sound-induced mechanical vibrations into neural impulses, which are interpreted by the brain and evoke the emotional effects. In the last decade; however, several studies suggest that the response to music is even more complex. Moreover, recent evidence comes out that cell types other than auditory hair cells could response to audible sound. However, what is actually sensed by the hair cells, and possible by other cells in our organism, are physical differences in fluid pressure induced by the sound waves. Therefore, there is no reasonable impediment for any cell type of our body to respond to a pure sound or to music. Hence, the aim of the present study was to evaluate the response of a human breast cancer cell line, MCF7, to music. The results′ obtained suggest that music can alter cellular morpho-functional parameters, such as cell size and granularity in cultured cells. Moreover, our results suggest for the 1 st time that music can directly interfere with hormone binding to their targets, suggesting that music or audible sounds could modulate physiological and pathophysiological processes.

  6. Direct effects of music in non-auditory cells in culture.

    Science.gov (United States)

    Lestard, Nathalia Dos Reis; Valente, Raphael C; Lopes, Anibal G; Capella, Márcia A M

    2013-01-01

    The biological effects of electromagnetic waves are widely studied, especially due to their harmful effects, such as radiation-induced cancer and to their application in diagnosis and therapy. However, the biological effects of sound, another physical agent to which we are frequently exposed have been considerably disregarded by the scientific community. Although a number of studies suggest that emotions evoked by music may be useful in medical care, alleviating stress and nociception in patients undergoing surgical procedures as well as in cancer and burned patients, little is known about the mechanisms by which these effects occur. It is generally accepted that the mechanosensory hair cells in the ear transduce the sound-induced mechanical vibrations into neural impulses, which are interpreted by the brain and evoke the emotional effects. In the last decade; however, several studies suggest that the response to music is even more complex. Moreover, recent evidence comes out that cell types other than auditory hair cells could response to audible sound. However, what is actually sensed by the hair cells, and possible by other cells in our organism, are physical differences in fluid pressure induced by the sound waves. Therefore, there is no reasonable impediment for any cell type of our body to respond to a pure sound or to music. Hence, the aim of the present study was to evaluate the response of a human breast cancer cell line, MCF7, to music. The results' obtained suggest that music can alter cellular morpho-functional parameters, such as cell size and granularity in cultured cells. Moreover, our results suggest for the 1 st time that music can directly interfere with hormone binding to their targets, suggesting that music or audible sounds could modulate physiological and pathophysiological processes. PMID:23955127

  7. Constructing skin-equivalents using hair follicle stem cells

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To establish the method of constructing skin-equivalents (SE) using hair follicle stem cells(HFSC).Methods: K19 positive cells derived from hair were cultivated using serum-free medium KGM and seeded on dermal equivalents (DE).After the culture between the air-liquid interface for 14 days, SE were harvested and used for evaluation. Results: K19 positive cells chosen as HFSC were located in bulge of out root sheet in hair follicle. Cultivated HFSC could build a fully developed, multi-layered epidermis on the basis of DE, resembling the skin structure. Conclusion: HFSC located in out root sheet can differentiate into keratinocyte in vitro and be used for SE construction.

  8. Interaural attention modulates outer hair cell function

    OpenAIRE

    Srinivasan, Sridhar; Keil, Andreas; Stratis, Kyle; Osborne, A. Fletcher; Cerwonka, Colin; Wong, Jennifer; Rieger, Brenda L.; Polcz, Valerie; Smith, David W

    2014-01-01

    Mounting evidence suggests that auditory attention tasks may modulate the sensitivity of the cochlea by way of the corticofugal and the medial olivocochlear (MOC) efferent pathways. Here, we studied the extent to which a separate efferent tract, the “uncrossed” MOC, which functionally connects the two ears, mediates inter-aural selective attention. We compared distortion product otoacoustic emissions (DPOAEs) in one ear to binaurally-presented primaries, using an intermodal target detection t...

  9. Interaural attention modulates outer hair cell function.

    Science.gov (United States)

    Srinivasan, Sridhar; Keil, Andreas; Stratis, Kyle; Osborne, Aaron F; Cerwonka, Colin; Wong, Jennifer; Rieger, Brenda L; Polcz, Valerie; Smith, David W

    2014-12-01

    Mounting evidence suggests that auditory attention tasks may modulate the sensitivity of the cochlea by way of the corticofugal and the medial olivocochlear (MOC) efferent pathways. Here, we studied the extent to which a separate efferent tract, the 'uncrossed' MOC, which functionally connects the two ears, mediates inter-aural selective attention. We compared distortion product otoacoustic emissions (DPOAEs) in one ear with binaurally presented primaries, using an intermodal target detection task in which participants were instructed to report the occurrence of brief target events (visual changes, tones). Three tasks were compared under identical physical stimulation: (i) report brief tones in the ear in which DPOAE responses were recorded; (ii) report brief tones presented to the contralateral, non-recorded ear; and (iii) report brief phase shifts of a visual grating at fixation. Effects of attention were observed as parallel shifts in overall DPOAE contour level, with DPOAEs relatively higher in overall level when subjects ignored the auditory stimuli and attended to the visual stimulus, compared with both of the auditory-attending conditions. Importantly, DPOAE levels were statistically lowest when attention was directed to the ipsilateral ear in which the DPOAE recordings were made. These data corroborate notions that top-down mechanisms, via the corticofugal and medial efferent pathways, mediate cochlear responses during intermodal attention. New findings show attending to one ear can significantly alter the physiological response of the contralateral, unattended ear, probably through the uncrossed-medial olivocochlear efferent fibers connecting the two ears. PMID:25302959

  10. Recovery of vestibular function following hair cell destruction by streptomycin

    Science.gov (United States)

    Jones, T. A.; Nelson, R. C.

    1992-01-01

    Can the vestibular periphery of warm-blooded vertebrates recover functionally from severe sensory hair cell loss? Recent findings in birds suggest a mechanism for recovery but in fact no direct functional evidence has been reported. We produced vestibular hair cell lesions using the ototoxic agent streptomycin sulfate (600 mg/kg/day, 8 days, chicks, Gallus domesticus). Compound action potentials of the vestibular nerve were used as a direct measure of peripheral vestibular function. Vestibular thresholds, neural activation latencies and amplitudes were documented. Eight days of drug treatment elevated thresholds significantly (P morphologies including activation latencies and amplitudes required an additional 6-8 weeks.

  11. Response of human hair cortical cells to fractionated radiotherapy

    International Nuclear Information System (INIS)

    Hair cortical cell counting (HCCC) represents a non-invasive, in-vivo measure of cell kill in the human integument. Sixty-six patients undergoing conventionally fractionated, external beam radiotherapy for early stage carcinoma of the prostate had groin hair samples counted. This technique is a sensitive and reproducible measure of radiation effect and may have applicability as an in-vivo prediction tool or in the field of biological dosimetry. A repopulative follicular response occurring at 3-4 weeks may explain flattening of the dose response curve

  12. Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

    OpenAIRE

    León, Alex; Elgueda, Diego; Silva, María A.; Hamamé, Carlos M.; Delano, Paul H.

    2012-01-01

    Background The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory...

  13. A Review of Gene Delivery and Stem Cell Based Therapies for Regenerating Inner Ear Hair Cells

    Directory of Open Access Journals (Sweden)

    Michael S. Detamore

    2011-09-01

    Full Text Available Sensory neural hearing loss and vestibular dysfunction have become the most common forms of sensory defects, affecting millions of people worldwide. Developing effective therapies to restore hearing loss is challenging, owing to the limited regenerative capacity of the inner ear hair cells. With recent advances in understanding the developmental biology of mammalian and non-mammalian hair cells a variety of strategies have emerged to restore lost hair cells are being developed. Two predominant strategies have developed to restore hair cells: transfer of genes responsible for hair cell genesis and replacement of missing cells via transfer of stem cells. In this review article, we evaluate the use of several genes involved in hair cell regeneration, the advantages and disadvantages of the different viral vectors employed in inner ear gene delivery and the insights gained from the use of embryonic, adult and induced pluripotent stem cells in generating inner ear hair cells. Understanding the role of genes, vectors and stem cells in therapeutic strategies led us to explore potential solutions to overcome the limitations associated with their use in hair cell regeneration.

  14. Adjudin protects rodent cochlear hair cells against gentamicin ototoxicity via the SIRT3-ROS pathway

    OpenAIRE

    Quan, Yizhou; Xia, Li; Shao, Jiaxiang; Yin, Shankai; Cheng, C. Yan; Xia, Weiliang; Gao, Wei-Qiang

    2015-01-01

    Hearing loss resulting from hair cell degeneration is a common disease that affects millions of people worldwide. Strategies to overcome the apparent irreversible hair cell loss in mammals become paramount for hearing protection. Here we reported that, by using a well-established gentamicin-induced hair cell loss model in vitro, adjudin, a multi-functional small molecule drug, protected cochlear hair cells from gentamicin damage. Immunohistochemistry, Western blotting and quantitative RT-PCR ...

  15. Inner ear hair cells produced in vitro by a mesenchymal-to-epithelial transition

    OpenAIRE

    Hu, Zhengqing; Corwin, Jeffrey T.

    2007-01-01

    Sensory hair cell loss is a major contributor to disabling hearing and balance deficits that affect >250 million people worldwide. Sound exposures, infections, drug toxicity, genetic disorders, and aging all can cause hair cell loss and lead to permanent sensory deficits. Progress toward treatments for these deficits has been limited, in part because hair cells have only been obtainable via microdissection of the anatomically complex internal ear. Attempts to produce hair cells in vitro have ...

  16. The Morphology and Cell Biology of the Hair Apparatus : Recent Advances

    OpenAIRE

    Ito, Masaaki

    1990-01-01

    Recent advances in knowledge of the morphology and biology of hair apparatuses are introduced. The hair apparatus morphologically shows a cyclic change "hair cycle" from anagen through catagen to telogen. In anagen, the hair apparatus is composed of eight epithelial cell layers, one of which has been very recently discovered: the innermost cell layer of the outer root sheath. When the ultrastructures of these cell layers are compared with each other, the cells of each layer reveal unique ultr...

  17. Hair Cell Generation by Notch Inhibition in the Adult Mammalian Cristae

    OpenAIRE

    Slowik, Amber D.; Bermingham-McDonogh, Olivia

    2013-01-01

    Balance disorders caused by hair cell loss in the sensory organs of the vestibular system pose a significant health problem worldwide, particularly in the elderly. Currently, this hair cell loss is permanent as there is no effective treatment. This is in stark contrast to nonmammalian vertebrates who robustly regenerate hair cells after damage. This disparity in regenerative potential highlights the need for further manipulation in order to stimulate more robust hair cell regeneration in mamm...

  18. Comparative transduction mechanisms of hair cells in the bullfrog utriculus. 1: Responses to intracellular current

    Science.gov (United States)

    Baird, Richard A.

    1994-01-01

    Hair cells in the bullfrog sacculus are specifically adapted to sense small-amplitude, high-frequency linear accelerations. These hair cells display many properties that are undesirable or inappropriate for hair cells that must provide static gravity sensitivity. This study resulted in part due to an interest in seeing how the transduction mechanisms of hair cells in a gravity-sensing otolith endorgan would differ from those in the bullfrog sacculus. The bullfrog utriculus is an appropriate model for these studies, because its structure is representative of higher vertebrates in general and its function as a sensor of static gravity and dynamic linear acceleration is well known. Hair cells in the bullfrog utriculus, classifiable as Type 2 by cell body and synapse morphology, differ markedly in hair bundle morphology from those in the bullfrog sacculus. Moreover, the hair bundle morphologies of utricular hair cells, unlike those in the sacculus, differ in different membrane regions.

  19. Inhibition of K+ currents in type I vestibular hair cells by gentamicin and neomycin.

    Science.gov (United States)

    Mann, Scott E; Johnson, Matthew; Meredith, Frances L; Rennie, Katherine J

    2013-01-01

    Significant ototoxicity limits the use of aminoglycoside (AG) antibiotics. Several mechanisms may contribute to the death of both auditory and vestibular hair cells. In this study the effects of gentamicin and neomycin on K(+) currents in mature and early postnatal type I vestibular hair cells (HCI) were tested directly. The whole-cell patch clamp technique was used to assess the effects of AG and KCNQ channel modulators on K(+) currents (IK) in HCI acutely isolated from gerbil semicircular canals. Extracellular neomycin (1 mM) rapidly reduced peak outward IK by 16 ± 4% (n = 9) in mature HCI (postnatal days, P, 25-66). Gentamicin (5 mM) reduced outward IK by 16 ± 3% (n = 8). A similar reduction in outward current was seen in immature HCI (P5-9) that lacked the low-voltage-activated component of IK observed in mature cells. Intracellular application of gentamicin and neomycin also reduced IK in mature HCI. Modulators of KCNQ channels were used to probe KCNQ channel involvement. The selective KCNQ antagonist XE991 did not reduce IK and the neomycin-induced reduction in IK was not reversed by the KCNQ agonist flupirtine. Application of intracellular poly-D-lysine to sequester PIP2 did not reduce IK. Application of the K(+) channel blocker 4-aminopyridine (4-AP) strongly reduced IK, and extracellular AG in the presence of 4-AP gave no further inhibition of IK. In summary, AG significantly reduce the 4-AP-sensitive IK in early postnatal and mature HCI. K(+) current inhibition differs from that seen in outer hair cells, since it does not appear to involve PIP2 sequestration or KCNQ channels. PMID:24051519

  20. Conditioning the cochlea to facilitate survival and integration of exogenous cells into the auditory epithelium.

    Science.gov (United States)

    Park, Yong-Ho; Wilson, Kevin F; Ueda, Yoshihisa; Tung Wong, Hiu; Beyer, Lisa A; Swiderski, Donald L; Dolan, David F; Raphael, Yehoash

    2014-04-01

    The mammalian auditory epithelium (AE) cannot replace supporting cells and hair cells once they are lost. Therefore, sensorineural hearing loss associated with missing cells is permanent. This inability to regenerate critical cell types makes the AE a potential target for cell replacement therapies such as stem cell transplantation. Inserting stem cells into the AE of deaf ears is a complicated task due to the hostile, high potassium environment of the scala media in the cochlea, and the robust junctional complexes between cells in the AE that resist stem cell integration. Here, we evaluate whether temporarily reducing potassium levels in the scala media and disrupting the junctions in the AE make the cochlear environment more receptive and facilitate survival and integration of transplanted cells. We used sodium caprate to transiently disrupt the AE junctions, replaced endolymph with perilymph, and blocked stria vascularis pumps with furosemide. We determined that these three steps facilitated survival of HeLa cells in the scala media for at least 7 days and that some of the implanted cells formed a junctional contact with native AE cells. The data suggest that manipulation of the cochlear environment facilitates survival and integration of exogenously transplanted HeLa cells in the scala media. PMID:24394296

  1. Restorative effect of hair follicular dermal cells on injured human hair follicles in a mouse model.

    Science.gov (United States)

    Yamao, Mikaru; Inamatsu, Mutsumi; Okada, Taro; Ogawa, Yuko; Ishida, Yuji; Tateno, Chise; Yoshizato, Katsutoshi

    2015-03-01

    No model is available for examining whether in vivo-damaged human hair follicles (hu-HFs) are rescued by transplanting cultured hu-HF dermal cells (dermal papilla and dermal sheath cells). Such a model might be valuable for examining whether in vivo-damaged hu-HFs such as miniaturized hu-HFs in androgenic alopecia are improvable by auto-transplanting hu-HF dermal cells. In this study, we first developed mice with humanized skin composed of hu-keratinocytes and hu-dermal fibroblasts. Then, a 'humanized scalp model mouse' was generated by transplanting hu-scalp HFs into the humanized skin. To demonstrate the usability of the model, the lower halves of the hu-HFs in the model were amputated in situ, and cultured hu-HF dermal cells were injected around the amputated area. The results demonstrated that the transplanted cells contributed to the restoration of the damaged HFs. This model could be used to explore clinically effective technologies for hair restoration therapy by autologous cell transplantation. PMID:25557326

  2. [High resolution scanning electron microscopy of isolated outer hair cells].

    Science.gov (United States)

    Koitschev, A; Müller, H

    1996-11-01

    Isolated hair cell preparations have gained wide acceptance as a model for studying physiological and molecular properties of the sensory cells involved in the hearing process. Ultrastructural details, such as stereocilia links, lateral membrane substructure or synaptic links are of crucial importance for normal sensory transduction. For this reason, we developed a high-resolution scanning electron microscopy (SEM) procedure to study the surface of isolated hair cells. Cells were mechanically and/or enzymatically separated, isolated and immobilized on cover slips by alcian blue and fixed by 2% glutardialdehyde or 1% OsO4. After dehydration, preparations were critical point-dried and sputter-coated with gold-palladium (2-4 nm). Up to 5 nm resolution was achieved. Optimal fixation kept the cells in their typical cylindrical forms. Preservation of the stereocilia and the apical plates of the outer hair cells depended strongly on the fixation process. Tip- and side-links were observed only sporadically because of the aggressive preparation procedure. The lateral plasma membranes of the cell bodies showed regular granular structures of 5-7 nm diameter at maximal magnification. The granular structure of the cell membrane seemed to correspond to putative transmembrane proteins believed to generate membrane-based motility. The remnants of the nerve endings and/or supporting cells usually covered the cell base. The preservation of the cells was better when enzymatic isolation was omitted. The technique used allowed for high resolution ultrastructural examination of isolated hair cells and, when combined with immunological labeling, may permit the identification of proteins at a molecular level. PMID:9064297

  3. Hair cell regeneration in the bullfrog vestibular otolith organs following aminoglycoside toxicity

    Science.gov (United States)

    Baird, Richard A.; Torres, M. A.; Schuff, N. R.

    1994-01-01

    Adult bullfrogs were given single intraotic injections of the aminoglycoside antibiotic gentamicin sulfate and sacrificed at postinjection times ranging from 0.5 to 9 days. The saccular and utricular maculae of normal and injected animals were examined in wholemount and cross-section. Intraotic 200 (mu) M gentamicin concentrations resulted in the uniform destruction of the hair bundles and, at later times, the cell bodies of saccular hair cells. In the utriculus, striolar hair cells were selectively damaged while extrastriolar hair cells were relatively unaffected. Regenerating hair cells, identified in sectioned material by their small cell bodies and short, well-formed hair bundles, were seen in the saccular and utricular maculae as early as 24-48 h postinjection. Immature versions of mature hair cell types in both otolith organs were recognized by the presence of absence of a bulbed kinocilia and the relative lengths of their kinocilia and longest sterocilia. Utricular hair cell types with kinocilia longer than their longest stereocilia were observed at earlier times than hair cell types with shorter kinocilia. In the same sacculus, the hair bundles of gentamicin-treated animals, even at 9 days postinjection, were significantly smaller than those of normal animals. The hair bundles of utricular hair cells, on the other hand, reached full maturity within the same time period.

  4. Cell death (apoptosis) in hair follicles and consequent changes in the width of hairs after irradiation of growing follicles

    International Nuclear Information System (INIS)

    Irradiation of anagen (growing) hair follicles results in a dose-dependent increase in the number of histologically identifiable fragments of dead cells (apoptotic fragments). The incidence of apoptotic fragments is linearly related to dose, increasing at a rate of 2.92 fragments per follicle section per gy. The effects of doses of 0.2 Gy can be easily detected. Subjective attempts to associate clusters of fragments with dead or dying cells suggests that the number of fragments per cell increases with dose (about 1.7 fragments per cell after 1 Gy to about 2.7 fragments per cell after 5 Gy). There is a natural incidence of cell death in controls (0.13 +- 0.06 fragments per follicle section with about 1.4 fragments per dead or dying cell). Damage to the follicle cells is expressed in the differentiated product of the follicle, the hair, by a reduction in width. This is probably the cellular basis for the production of dysplastic hairs. The hair width has been measured and is reduced by about 7% for every gray of radiation. The value of the hair and hair follicles as potential biological dosimeters is discussed. (author)

  5. Derivation of cochlea hair cell for in vitro expansion and characterization.

    Science.gov (United States)

    Ibnubaidah, M A; Chua, K H; Mazita, A; Azida, Z N; Aminuddin, B S; Ruszymah, B H I; Lokman, B S

    2008-07-01

    A potential cure for hearing loss would be to regenerate hair cells by stimulating cells of the damaged inner ear sensory epithelia to proliferate and differentiate into hair cells. Here, we investigated the possibility to isolate, culture-expand and characterize the cells from the cochlea membrane of adult mice. Our results showed that the cultured cells isolated from mouse cochlea membrane were heterogenous in nature. Morphologically there were epithelial like cells, hair cell like, nerve cell like and fibroblastic cells observed in the culture. The cultured cells were immunopositive for specific hair cell markers including Myosin 7a, Calretinin and Espin. PMID:19025012

  6. Aminoglycoside antibiotics and the sensory hair cells of inner ear and lateral line system in the Atlantic cod, Gadus morhua: effects on fish hearing threshold

    OpenAIRE

    Faucher, Karine; Aas-Hansen, Øyvind; Damsgard, Borge; Bégout, Marie-Laure; Fuhr, Torgrim; Laukli, Einar; Stenklev, Niels-Christian

    2007-01-01

    The aims of the present study were to investigate: a) the potential involvement of the fish lateral line system in hearing at 250 Hz and b) the possible regeneration of the inner ear hair cells in the Atlantic cod (Gadus morhua). The inner ear and lateral line system of the Atlantic cod were inactivated using ototoxic aminoglycoside antibiotics by injection (gentamicin) or bath (gentamicin and streptomycin), respectively. Hearing thresholds were measured in the fish using the Auditory Brainst...

  7. A membrane bending model of outer hair cell electromotility.

    OpenAIRE

    Raphael, R. M.; Popel, A S; Brownell, W. E.

    2000-01-01

    We propose a new mechanism for outer hair cell electromotility based on electrically induced localized changes in the curvature of the plasma membrane (flexoelectricity). Electromechanical coupling in the cell's lateral wall is modeled in terms of linear constitutive equations for a flexoelectric membrane and then extended to nonlinear coupling based on the Langevin function. The Langevin function, which describes the fraction of dipoles aligned with an applied electric field, is shown to be ...

  8. Micropipette aspiration on the outer hair cell lateral wall.

    OpenAIRE

    Sit, P S; Spector, A A; Lue, A J; Popel, A S; Brownell, W.E.

    1997-01-01

    The mechanical properties of the lateral wall of the guinea pig cochlear outer hair cell were studied using the micropipette aspiration technique. A fire-polished micropipette with an inner diameter of approximately 4 microm was brought into contact with the lateral wall and negative pressure was applied. The resulting deformation of the lateral wall was recorded on videotape and subjected to morphometric analysis. The relation between the length of the aspirated portion of the cell and aspir...

  9. Reciprocal Innervation of Outer Hair Cells in a Human Infant

    OpenAIRE

    Thiers, Fabio A.; Burgess, Barbara J.; Nadol, Joseph B.

    2002-01-01

    Reciprocal synapses are characterized by the presence of both afferent and efferent types of synaptic specializations between two cells. They have been described at the neural poles of outer hair cells (OHCs) in humans with advanced age and two monkey species. Our objective was to study the innervation of the OHCs and determine if reciprocal synapses were present in a young (8-month-old infant) human subject. We studied the synaptic and cytoplasmic morphology of 162 nerve terminals innervatin...

  10. Coupling a sensory hair-cell bundle to cyber clones enhances nonlinear amplification

    OpenAIRE

    Barral, Jérémie; Dierkes, Kai; Lindner, Benjamin; Jülicher, Frank; Martin, Pascal

    2010-01-01

    The vertebrate ear benefits from nonlinear mechanical amplification to operate over a vast range of sound intensities. The amplificatory process is thought to emerge from active force production by sensory hair cells. The mechano-sensory hair bundle that protrudes from the apical surface of each hair cell can oscillate spontaneously and function as a frequency-selective, nonlinear amplifier. Intrinsic fluctuations, however, jostle the response of a single hair bundle to weak stimuli and serio...

  11. Culture and characterization of rat hair follicle stem cells.

    Science.gov (United States)

    Quan, Renfu; Zheng, Xuan; Ni, Yueming; Xie, Shangju; Li, Changming

    2016-08-01

    The purpose of this study was to establish methods for isolation, culture, expansion, and characterization of rat hair follicle stem cells (rHFSCs). Hair follicles were harvested from 1-week-old Sprague-Dawley rats and digested with dispase and collagenase IV. The bulge of the hair follicle was dissected under a microscope and cultured in Dulbecco's modified Eagle's medium/F12 supplemented with KnockOut™ Serum Replacement serum substitute, penicillin-streptomycin, L-glutamine, non-essential amino acids, epidermal growth factor, basic fibroblast growth factor, polyhydric alcohol, and hydrocortisone. The rHFSCs were purified using adhesion to collagen IV. Cells were characterized by detecting marker genes with immunofluorescent staining and real-time polymerase chain reaction (PCR). The proliferation and vitality of rHFSCs at different passages were evaluated. The cultured rHFSCs showed typical cobblestone morphology with good adhesion and colony-forming ability. Expression of keratin 15, integrin α6, and integrin β1 were shown by immunocytochemistry staining. On day 1-2, the cells were in the latent phase. On day 5-6, the cells were in the logarithmic phase. Cell vitality gradually decreased from the 7th passage. Real-time PCR showed that the purified rHFSCs had good vitality and proliferative capacity and contained no keratinocytes. Highly purified rHFSCs can be obtained using tissue culture and adhesion to collagen IV. The cultured cells had good proliferative capacity and could therefore be a useful cell source for tissue-engineered hair follicles, vessels, and skin. PMID:25407732

  12. Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

    Science.gov (United States)

    Barclay, M; Constable, R; James, N R; Thorne, P R; Montgomery, J M

    2016-06-14

    Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC. PMID:27012610

  13. Spatial and Age-Dependent Hair Cell Generation in the Postnatal Mammalian Utricle.

    Science.gov (United States)

    Gao, Zhen; Kelly, Michael C; Yu, Dehong; Wu, Hao; Lin, Xi; Chi, Fang-Lu; Chen, Ping

    2016-04-01

    Loss of vestibular hair cells is a common cause of balance disorders. Current treatment options for bilateral vestibular dysfunction are limited. During development, atonal homolog 1 (Atoh1) is sufficient and necessary for the formation of hair cells and provides a promising gene target to induce hair cell generation in the mammals. In this study, we used a transgenic mouse line to test the age and cell type specificity of hair cell induction in the postnatal utricle in mice. We found that forced Atoh1 expression in vivo can induce hair cell formation in the utricle from postnatal days 1 to 21, while the efficacy of hair cell induction is progressively reduced as the animals become older. In the utricle, the induction of hair cells occurs both within the sensory region and in cells in the transitional epithelium next to the sensory region. Within the sensory epithelium, the central region, known as the striola, is most subjective to the induction of hair cell formation. Furthermore, forced Atoh1 expression can promote proliferation in an age-dependent manner that mirrors the progressively reduced efficacy of hair cell induction in the postnatal utricle. These results suggest that targeting both cell proliferation and Atoh1 in the utricle striolar region may be explored to induce hair cell regeneration in mammals. The study also demonstrates the usefulness of the animal model that provides an in vivo Atoh1 induction model for vestibular regeneration studies. PMID:25666161

  14. Comparative transduction mechanisms of hair cells in the bullfrog utriculus. II. Sensitivity and response dynamics to hair bundle displacement

    Science.gov (United States)

    Baird, R. A.

    1994-01-01

    1. Hair cells in whole-mount in vitro preparations of the utricular macula of the bullfrog (Rana catesbeiana) were selected according to their macular location and hair bundle morphology. The sensitivity and response dynamics of selected hair cells to natural stimulation were examined by recording their voltage responses to step and sinusoidal hair bundle displacements applied to their longest stereocilia. 2. The voltage responses of 31 hair cells to sinusoidal hair bundle displacements were characterized by their gains and phases, taken with respect to peak hair bundle displacement. The gains of Type B and Type C cells at both 0.5 and 5.0 Hz were markedly lower than those of Type F and Type E cells. Phases, with the exception of Type C cells, lagged hair bundle displacement at 0.5 Hz. Type C cells had phase leads of 25-40 degrees. At 5.0 Hz, response phases in all cells were phase lagged with respect to those at 0.5 Hz. Type C cells had larger gains and smaller phase leads at 5.0 Hz than at 0.5 Hz, suggesting the presence of low-frequency adaptation. 3. Displacement-response curves, derived from the voltage responses to 5.0-Hz sinusoids, were sigmoidal in shape and asymmetrical, with the depolarizing response having a greater magnitude and saturating less abruptly than the hyperpolarizing response. When normalized to their largest displacement the linear ranges of these curves varied from hair bundle to linear range and sensitivity were predicted from realistic models of utricular hair bundles created using morphological data obtained from light and electron microscopy. Three factors, including 1) the inverse ratio of the lengths of the kinocilium and longest stereocilia, representing the lever arm between kinociliary and stereociliary displacement; 2) tip link extension/linear displacement, largely a function of stereociliary height and separation; and 3) stereociliary number, an estimate of the number of transduction channels, were considered in this analysis

  15. Comparative transduction mechanisms of hair cells in the bullfrog utriculus. II. Sensitivity and response dynamics to hair bundle displacement

    Science.gov (United States)

    Baird, R. A.

    1994-01-01

    1. Hair cells in whole-mount in vitro preparations of the utricular macula of the bullfrog (Rana catesbeiana) were selected according to their macular location and hair bundle morphology. The sensitivity and response dynamics of selected hair cells to natural stimulation were examined by recording their voltage responses to step and sinusoidal hair bundle displacements applied to their longest stereocilia. 2. The voltage responses of 31 hair cells to sinusoidal hair bundle displacements were characterized by their gains and phases, taken with respect to peak hair bundle displacement. The gains of Type B and Type C cells at both 0.5 and 5.0 Hz were markedly lower than those of Type F and Type E cells. Phases, with the exception of Type C cells, lagged hair bundle displacement at 0.5 Hz. Type C cells had phase leads of 25-40 degrees. At 5.0 Hz, response phases in all cells were phase lagged with respect to those at 0.5 Hz. Type C cells had larger gains and smaller phase leads at 5.0 Hz than at 0.5 Hz, suggesting the presence of low-frequency adaptation. 3. Displacement-response curves, derived from the voltage responses to 5.0-Hz sinusoids, were sigmoidal in shape and asymmetrical, with the depolarizing response having a greater magnitude and saturating less abruptly than the hyperpolarizing response. When normalized to their largest displacement the linear ranges of these curves varied from Sensitivity, defined as the slope of the normalized displacement-response curve, was inversely correlated with linear range. 4. The contribution of geometric factors associated with the hair bundle to linear range and sensitivity were predicted from realistic models of utricular hair bundles created using morphological data obtained from light and electron microscopy. Three factors, including 1) the inverse ratio of the lengths of the kinocilium and longest stereocilia, representing the lever arm between kinociliary and stereociliary displacement; 2) tip link extension

  16. Epigenetic DNA Demethylation Causes Inner Ear Stem Cell Differentiation into Hair Cell-Like Cells

    Science.gov (United States)

    Zhou, Yang; Hu, Zhengqing

    2016-01-01

    The DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-aza) causes genomic demethylation to regulate gene expression. However, it remains unclear whether 5-aza affects gene expression and cell fate determination of stem cells. In this study, 5-aza was applied to mouse utricle sensory epithelia-derived progenitor cells (MUCs) to investigate whether 5-aza stimulated MUCs to become sensory hair cells. After treatment, MUCs increased expression of hair cell genes and proteins. The DNA methylation level (indicated by percentage of 5-methylcytosine) showed a 28.57% decrease after treatment, which causes significantly repressed DNMT1 protein expression and DNMT activity. Additionally, FM1-43 permeation assays indicated that the permeability of 5-aza-treated MUCs was similar to that of sensory hair cells, which may result from mechanotransduction channels. This study not only demonstrates a possible epigenetic approach to induce tissue specific stem/progenitor cells to become sensory hair cell-like cells, but also provides a cell model to epigenetically modulate stem cell fate determination. PMID:27536218

  17. Spontaneous and Partial Repair of Ribbon Synapse in Cochlear Inner Hair Cells After Ototoxic Withdrawal.

    Science.gov (United States)

    Liu, Ke; Chen, DaiShi; Guo, WeiWei; Yu, Ning; Wang, XiaoYu; Ji, Fei; Hou, ZhaoHui; Yang, Wei-Yan; Yang, ShiMing

    2015-12-01

    Ototoxicity is one of the major causes of sensorineural deafness. However, it remains unclear whether sensorineural deafness is reversible after ototoxic withdrawal. Here, we report that the ribbon synapses between the inner hair cells (IHCs) and spiral ganglion nerve (SGN) fibers can be restored after ototoxic trauma. This corresponds with hearing restoration after ototoxic withdrawal. In this study, adult mice were injected daily with a low dose of gentamicin for 14 consecutive days. Immunostaining for RIBEYE/CtBP2 was used to estimate the number and size of synaptic ribbons in the cochlea. Hearing thresholds were assessed using auditory brainstem responses. Auditory temporal processing between IHCs and SGNs was evaluated by compound action potentials. We found automatic hearing restoration after ototoxicity withdrawal, which corresponded to the number and size recovery of synaptic ribbons, although both hearing and synaptic recovery were not complete. Thus, our study indicates that sensorineural deafness in mice can be reversible after ototoxic withdrawal due to an intrinsic repair of ribbon synapse in the cochlea. PMID:25377793

  18. Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling

    OpenAIRE

    Kandyba, Eve; Kobielak, Krzysztof

    2014-01-01

    The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis and progeny differentiation. During morphogenesis, Wnt signaling is well characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required and whether individual Wnt ligands act in an indispensable or redundant manner during postnatal hfSCs anagen onset and HF cycle progression. Previo...

  19. Inexhaustible hair-cell regeneration in young and aged zebrafish

    Directory of Open Access Journals (Sweden)

    Filipe Pinto-Teixeira

    2015-07-01

    Full Text Available Animals have evolved two general strategies to counter injury and maintain physiological function. The most prevalent is protection by isolating vital organs into body cavities. However, protection is not optimal for sensory systems because their external components need to be exposed to the environment to fulfill their receptive function. Thus, a common strategy to maintain sensory abilities against persistent environmental insult involves repair and regeneration. However, whether age or frequent injuries affect the regenerative capacity of sensory organs remains unknown. We have found that neuromasts of the zebrafish lateral line regenerate mechanosensory hair cells after recurrent severe injuries and in adulthood. Moreover, neuromasts can reverse transient imbalances of Notch signaling that result in defective organ proportions during repair. Our results reveal inextinguishable hair-cell regeneration in the lateral line, and suggest that the neuromast epithelium is formed by plastic territories that are maintained by continuous intercellular communication.

  20. Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation.

    Science.gov (United States)

    Shirokova, Vera; Biggs, Leah C; Jussila, Maria; Ohyama, Takahiro; Groves, Andrew K; Mikkola, Marja L

    2016-07-01

    The hair follicle is an ideal system to study stem cell specification and homeostasis due to its well characterized morphogenesis and stereotypic cycles of stem cell activation upon each hair cycle to produce a new hair shaft. The adult hair follicle stem cell niche consists of two distinct populations, the bulge and the more activation-prone secondary hair germ (HG). Hair follicle stem cells are set aside during early stages of morphogenesis. This process is known to depend on the Sox9 transcription factor, but otherwise the establishment of the hair follicle stem cell niche is poorly understood. Here, we show that that mutation of Foxi3, a Forkhead family transcription factor mutated in several hairless dog breeds, compromises stem cell specification. Further, loss of Foxi3 impedes hair follicle downgrowth and progression of the hair cycle. Genome-wide profiling revealed a number of downstream effectors of Foxi3 including transcription factors with a recognized function in hair follicle stem cells such as Lhx2, Runx1, and Nfatc1, suggesting that the Foxi3 mutant phenotype results from simultaneous downregulation of several stem cell signature genes. We show that Foxi3 displays a highly dynamic expression pattern during hair morphogenesis and cycling, and identify Foxi3 as a novel secondary HG marker. Absence of Foxi3 results in poor hair regeneration upon hair plucking, and a sparse fur phenotype in unperturbed mice that exacerbates with age, caused by impaired secondary HG activation leading to progressive depletion of stem cells. Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. Stem Cells 2016;34:1896-1908. PMID:26992132

  1. Streptomycin ototoxicity and hair cell regeneration in the adult pigeon utricle

    Science.gov (United States)

    Frank, T. C.; Dye, B. J.; Newlands, S. D.; Dickman, J. D.

    1999-01-01

    OBJECTIVE: The purpose of this study was to develop a technique to investigate the regeneration of utricular hair cells in the adult pigeon (Columba livia) following complete hair cell loss through administration of streptomycin. STUDY DESIGN: Experimental animal study. METHODS: Animals were divided into four groups. Group 1 received 10 to 15 days of systemic streptomycin injections. Animals in Groups 2 and 3 received a single direct placement of a 1-, 2-, 4-, or 8-mg streptomycin dose into the perilymphatic space. Animals in Groups 1 and 2 were analyzed within 1 week from injection to investigate hair cell destruction, whereas Group 3 was investigated at later dates to study hair cell recovery. Group 4 animals received a control injection of saline into the perilymphatic space. Damage and recovery were quantified by counting hair cells in isolated utricles using scanning electron microscopy. RESULTS: Although systemic injections failed to reliably achieve complete utricular hair cell destruction, a single direct placement of a 2-, 4-, or 8-mg streptomycin dose caused complete destruction within the first week. Incomplete hair cell loss was observed with the 1-mg dose. Over the long term, regeneration of the hair cells was seen with the 2-mg dose but not the 8-mg dose. Control injections of saline into the perilymphatic space caused no measurable hair cell loss. CONCLUSIONS: Direct placement of streptomycin into the perilymph is an effective, reliable method for complete destruction of utricular hair cells while preserving the regenerative potential of the neuroepithelium.

  2. The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

    OpenAIRE

    Anna Kirjavainen; Maarja Laos; Tommi Anttonen; Ulla Pirvola

    2015-01-01

    Hair cells of the organ of Corti (OC) of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubul...

  3. Evaluation of peripheral compression and auditory nerve fiber intensity coding using auditory steady-state responses

    DEFF Research Database (Denmark)

    Encina Llamas, Gerard; M. Harte, James; Epp, Bastian

    2015-01-01

    . Evaluation of these properties provides information about the health state of the system. It has been shown that a loss of outer hair cells leads to a reduction in peripheral compression. It has also recently been shown in animal studies that noise over-exposure, producing temporary threshold shifts, can......The compressive nonlinearity of the auditory system is assumed to be an epiphenomenon of a healthy cochlea and, particularly, of outer-hair cell function. Another ability of the healthy auditory system is to enable communication in acoustical environments with high-level background noises...

  4. Biological characterization of cultured dermal papilla cells and hair follicle regeneration in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Lü Zhong-fa; CAI Sui-qing; WU Jin-jin; ZHENG Min

    2006-01-01

    Background Dermal papilla cells (DPC) are a group of mesenchyme-derived cells at the base of the hair follicle, where they regulate and control hair follicle growth through the expression and secretion of cytokines. Nevertheless, the role of DPC derived chemokines and other cytokines in the hair follicle biology remain speculative. In this study, we investigated the expression of basic fibroblast growth factor (bFGF), endothelin-1 (ET-1) and stem cell factor (SCF) in different passages of cultured DPC and their effects on the biological behaviour of DPC.Methods The expression of bFGF, ET-1 and SCF in different passages of cultured DPC and their possible effects on the biological behavior of DPC are investigated using in situ hybridization and immunochemistry. In addition, we performed transplantation of hair follicle cells into nude mice. The cultured DPC, dermal sheath cells and fibroblast of human scalp, respectively, were mixed with cells of the hair follicle epithelium in different ratios, and then were cultured in hair follicle organotypic cultures or implanted into the subcutis of nude mice.Results The expression of ET-1 and SCF in early passages of cultured DPC became stronger, but turned weaker and even negative in late passages (>6 passages). Hair follicle-like structures were formed after DPC combined with the cells of hair follicle epithelium cells in hair follicle organotypic cultures. When hair follicle organotypic cultures were implanted into the subcutis of nude mice, the relative intact hair follicles were formed. After the transplantation of hair follicle cells into the nude mice, the hair follicle-like structure was formed in the group that contained DPC mixed with hair follicle epithelium cells. However, no hair follicles were formed in the other two groups. It was found that the higher the expression of ET-1 and SCF in DPC, the stronger the ability of DPC to induce hair follicle regeneration.Conclusions The cultured DPC can induce hair follicle

  5. Calbindin and parvalbumin are early markers of non-mitotically regenerating hair cells in the bullfrog vestibular otolith organs

    Science.gov (United States)

    Steyger, P. S.; Burton, M.; Hawkins, J. R.; Schuff, N. R.; Baird, R. A.

    1997-01-01

    Earlier studies have demonstrated hair cell regeneration in the absence of cell proliferation, and suggested that supporting cells could phenotypically convert into hair cells following hair cell loss. Because calcium-binding proteins are involved in gene up-regulation, cell growth, and cell differentiation, we wished to determine if these proteins were up-regulated in scar formations and regenerating hair cells following gentamicin treatment. Calbindin and parvalbumin immunolabeling was examined in control or gentamicin-treated (GT) bullfrog saccular and utricular explants cultured for 3 days in amphibian culture medium or amphibian culture medium supplemented with aphidicolin, a blocker of nuclear DNA replication in eukaryotic cells. In control cultures, calbindin and parvalbumin immunolabeled the hair bundles and, less intensely, the cell bodies of mature hair cells. In GT or mitotically-blocked GT (MBGT) cultures, calbindin and parvalbumin immunolabeling was also seen in the hair bundles, cuticular plates, and cell bodies of hair cells with immature hair bundles. Thus, these antigens were useful markers for both normal and regenerating hair cells. Supporting cell immunolabeling was not seen in control cultures nor in the majority of supporting cells in GT cultures. In MBGT cultures, calbindin and parvalbumin immunolabeling was up-regulated in the cytosol of single supporting cells participating in scar formations and in supporting cells with hair cell-like characteristics. These data provide further evidence that non-mitotic hair cell regeneration in cultures can be accomplished by the conversion of supporting cells into hair cells.

  6. The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear

    OpenAIRE

    Mantela, Johanna; Jiang, Zhe; Ylikoski, Jukka; Fritzsch, Bernd; Zacksenhaus, Eldad; Pirvola, Ulla

    2005-01-01

    Precursors of cochlear and vestibular hair cells of the inner ear exit the cell cycle at midgestation. Hair cells are mitotically quiescent during late-embryonic differentiation stages and postnatally. We show here that the retinoblastoma gene Rb and the encoded protein pRb are expressed in differentiating and mature hair cells. In addition to Rb, the cyclin dependent kinase inhibitor (CKI) p21 is expressed in developing hair cells, suggesting that p21 is an upstream effector of pRb activity....

  7. High-Pass Filtering at Vestibular Frequencies by Transducer Adaptation in Mammalian Saccular Hair Cells

    Science.gov (United States)

    Songer, Jocelyn E.; Eatock, Ruth Anne

    2011-11-01

    The mammalian saccule detects head tilt and low-frequency head accelerations as well as higher-frequency bone vibrations and sounds. It has two different hair cell types, I and II, dispersed throughout two morphologically distinct regions, the striola and extrastriola. Afferents from the two zones have distinct response dynamics which may arise partly from zonal differences in hair cell properties. We find that type II hair cells in the rat saccular epithelium adapt with a time course appropriate for influencing afferent responses to head motions. Moreover, striolar type II hair cells adapted by a greater extent than extrastriolar type II hair cells and had greater phase leads in the mid-frequency range (5-50 Hz). These differences suggest that hair cell transduction may contribute to zonal differences in the adaptation of vestibular afferents to head motions.

  8. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Na [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Chen, Yan [Central Laboratory, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Wang, Zhengmin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Chen, Guoling [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Lin, Qin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology, First Affiliated Hospital of Fujian Medical University, Otolaryngology Institute of Fujian Province, Fuzhou (China); Chen, Zheng-Yi, E-mail: Zheng-yi_chen@meei.harvard.edu [Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Li, Huawei, E-mail: hwli@shmu.edu.cn [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Shh activation in neonatal cochleae enhances sensory cell proliferation. Black-Right-Pointing-Pointer Proliferating supporting cells can transdifferentiate into hair cells. Black-Right-Pointing-Pointer Shh promotes proliferation by transiently modulating pRb activity. Black-Right-Pointing-Pointer Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

  9. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    International Nuclear Information System (INIS)

    Highlights: ► Shh activation in neonatal cochleae enhances sensory cell proliferation. ► Proliferating supporting cells can transdifferentiate into hair cells. ► Shh promotes proliferation by transiently modulating pRb activity. ► Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

  10. Intrasaccular injection of aminoglycosides: a novel method for temporary damaging fish inner ear hair cells

    OpenAIRE

    Faucher, Karine; Aas-Hansen, Øyvind; Damsgard, Borge; Stenklev, Niels-Christian

    2008-01-01

    Fish models are increasingly being used for hearing research investigations. Aminoglycoside antibiotics that are used for damaging the inner ear hair cells can have systemic side effects leading to death of study animals. This study aimed to compare two methods: i) systemic (intravenous) and ii) local (intrasaccular) gentamicin administration for induction of inner ear hair cell damage in the Atlantic cod, Gadus morhua (L.). Hair cell damage was assessed using scanning electron microscopy; ha...

  11. Identification of Modulators of Hair Cell Regeneratin in the Zebrafish Lateral Line

    OpenAIRE

    Namdaran, Parhum; Reinhart, Katherine E.; Owens, Kelly N.; Raible, David W.; Rubel, Edwin W

    2012-01-01

    The external location of the zebrafish lateral line makes it a powerful model for studying mechanosensory hair cell regeneration. We have developed a chemical screen to identify FDA-approved drugs and biologically active compounds that modulate hair cell regeneration in zebrafish. Of the 1,680 compounds evaluated, we identified 2 enhancers and 6 inhibitors of regeneration. The two enhancers, dexamethasone and prednisolone, are synthetic glucocorticoids that potentiated hair cell numbers durin...

  12. Patch Clamp Recordings in Inner Ear Hair Cells Isolated from Zebrafish

    OpenAIRE

    Einarsson, Rachel; Haden, Marshall; DiCiolli, Gabrielle; Lim, Andrea; Mah-Ginn, Kolina; Aguilar, Kathleen; Yazejian, Lucy; Yazejian, Bruce

    2012-01-01

    Patch clamp analyses of the voltage-gated channels in sensory hair cells isolated from a variety of species have been described previously1-4 but this video represents the first application of those techniques to hair cells from zebrafish. Here we demonstrate a method to isolate healthy, intact hair cells from all of the inner ear end-organs: saccule, lagena, utricle and semicircular canals. Further, we demonstrate the diversity in hair cell size and morphology and give an example of the kind...

  13. Preliminary Characterization of Voltage-Activated Whole-Cell Currents in Developing Human Vestibular Hair Cells and Calyx Afferent Terminals

    OpenAIRE

    Lim, Rebecca; Drury, Hannah R.; Camp, Aaron J.; Tadros, Melissa A; Robert J Callister; Brichta, Alan M.

    2014-01-01

    We present preliminary functional data from human vestibular hair cells and primary afferent calyx terminals during fetal development. Whole-cell recordings were obtained from hair cells or calyx terminals in semi-intact cristae prepared from human fetuses aged between 11 and 18 weeks gestation (WG). During early fetal development (11–14 WG), hair cells expressed whole-cell conductances that were qualitatively similar but quantitatively smaller than those observed previously in mature rodent ...

  14. Aqueous Extract of Red Deer Antler Promotes Hair Growth by Regulating the Hair Cycle and Cell Proliferation in Hair Follicles

    OpenAIRE

    Jing-jie Li; Zheng Li; Li-juan Gu; Yun-bo Wang; Mi-ra Lee; Chang-keun Sung

    2014-01-01

    Deer antlers are the only mammalian appendage capable of regeneration. We aimed to investigate the effect of red deer antler extract in regulating hair growth, using a mouse model. The backs of male mice were shaved at eight weeks of age. Crude aqueous extracts of deer antler were prepared at either 4°C or 100°C and injected subcutaneously to two separate groups of mice (n = 9) at 1 mL/day for 10 consecutive days, with water as a vehicle control group. The mice skin quantitative hair growth p...

  15. Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

    Science.gov (United States)

    Yaghini, Omid

    2016-01-01

    Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency. PMID:27144235

  16. Macrophage Recruitment Contributes to Regeneration of Mechanosensory Hair Cells in the Zebrafish Lateral Line.

    Science.gov (United States)

    Carrillo, Simón A; Anguita-Salinas, Consuelo; Peña, Oscar A; Morales, Rodrigo A; Muñoz-Sánchez, Salomé; Muñoz-Montecinos, Carlos; Paredes-Zúñiga, Susana; Tapia, Karina; Allende, Miguel L

    2016-08-01

    In vertebrates, damage to mechanosensory hair cells elicits an inflammatory response, including rapid recruitment of macrophages and neutrophils. While hair cells in amniotes usually become permanently lost, they readily regenerate in lower vertebrates such as fish. Damage to hair cells of the fish lateral line is followed by inflammation and rapid regeneration; however the role of immune cells in this process remains unknown. Here, we show that recruited macrophages are required for normal regeneration of lateral line hair cells after copper damage. We found that genetic ablation or local ablation using clodronate liposomes of macrophages recruited to the site of injury, significantly delays hair cell regeneration. Neutrophils, on the other hand, are not needed for this process. We anticipate our results to be a starting point for a more detailed description of extrinsic signals important for regeneration of mechanosensory cells in vertebrates. J. Cell. Biochem. 117: 1880-1889, 2016. © 2016 Wiley Periodicals, Inc. PMID:26755079

  17. Neuronal differentiation and extensive migration of human neural precursor cells following co-culture with rat auditory brainstem slices.

    Directory of Open Access Journals (Sweden)

    Ekaterina Novozhilova

    Full Text Available Congenital or acquired hearing loss is often associated with a progressive degeneration of the auditory nerve (AN in the inner ear. The AN is composed of processes and axons of the bipolar spiral ganglion neurons (SGN, forming the connection between the hair cells in the inner ear cochlea and the cochlear nuclei (CN in the brainstem (BS. Therefore, replacement of SGNs for restoring the AN to improve hearing function in patients who receive a cochlear implantation or have severe AN malfunctions is an attractive idea. A human neural precursor cell (HNPC is an appropriate donor cell to investigate, as it can be isolated and expanded in vitro with maintained potential to form neurons and glia. We recently developed a post-natal rodent in vitro auditory BS slice culture model including the CN and the central part of the AN for initial studies of candidate cells. Here we characterized the survival, distribution, phenotypic differentiation, and integration capacity of HNPCs into the auditory circuitry in vitro. HNPC aggregates (spheres were deposited adjacent to or on top of the BS slices or as a monoculture (control. The results demonstrate that co-cultured HNPCs compared to monocultures (1 survive better, (2 distribute over a larger area, (3 to a larger extent and in a shorter time-frame form mature neuronal and glial phenotypes. HNPC showed the ability to extend neurites into host tissue. Our findings suggest that the HNPC-BS slice co-culture is appropriate for further investigations on the integration capacity of HNPCs into the auditory circuitry.

  18. TGF-β2 is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis

    OpenAIRE

    Inoue, Keita; Aoi, Noriyuki; Yamauchi, Yuji; Sato, Takahiro; Suga, Hirotaka; Eto, Hitomi; Kato, Harunosuke; Tabata, Yasuhiko; Yoshimura, Kotaro

    2009-01-01

    Dermal papilla cells (DPCs) in the mammalian hair follicle have been shown to develop hair follicles through epithelial–mesenchymal interactions. A cell therapy to regenerate human hair is theoretically possible by expanding autologous human DPCs (hDPCs) and transplanting them into bald skin, though much remains to be overcome before clinical success. In this study, we compared gene signatures of hDPCs at different passages and human dermal fibroblasts, and found transforming growth factor (T...

  19. Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline

    OpenAIRE

    Chi, Woo; Wu, Eleanor; Morgan, Bruce A.

    2013-01-01

    Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successiv...

  20. A simple method for purification of vestibular hair cells and non-sensory cells, and application for proteomic analysis.

    Directory of Open Access Journals (Sweden)

    Meike Herget

    Full Text Available Mechanosensitive hair cells and supporting cells comprise the sensory epithelia of the inner ear. The paucity of both cell types has hampered molecular and cell biological studies, which often require large quantities of purified cells. Here, we report a strategy allowing the enrichment of relatively pure populations of vestibular hair cells and non-sensory cells including supporting cells. We utilized specific uptake of fluorescent styryl dyes for labeling of hair cells. Enzymatic isolation and flow cytometry was used to generate pure populations of sensory hair cells and non-sensory cells. We applied mass spectrometry to perform a qualitative high-resolution analysis of the proteomic makeup of both the hair cell and non-sensory cell populations. Our conservative analysis identified more than 600 proteins with a false discovery rate of <3% at the protein level and <1% at the peptide level. Analysis of proteins exclusively detected in either population revealed 64 proteins that were specific to hair cells and 103 proteins that were only detectable in non-sensory cells. Statistical analyses extended these groups by 53 proteins that are strongly upregulated in hair cells versus non-sensory cells and vice versa by 68 proteins. Our results demonstrate that enzymatic dissociation of styryl dye-labeled sensory hair cells and non-sensory cells is a valid method to generate pure enough cell populations for flow cytometry and subsequent molecular analyses.

  1. Characterization of Rat Hair Follicle Stem Cells Selected by Vario Magnetic Activated Cell Sorting System

    International Nuclear Information System (INIS)

    Hair follicle stem cells (HfSCs) play crucial roles in hair follicle morphogenesis and hair cycling. These stem cells are self-renewable and have the multi-lineage potential to generate epidermis, sebaceous glands, and hair follicle. The separation and identification of hair follicle stem cells are important for further research in stem cell biology. In this study, we report on the successful enrichment of rat hair follicle stem cells through vario magnetic activated cell sorting (Vario MACS) and the biological characteristics of the stem cells. We chose the HfSCs positive surface markers CD34, α6-integrin and the negative marker CD71 to design four isolation strategies: positive selection with single marker of CD34, positive selection with single marker of α6-integrin, CD71 depletion followed by CD34 positive selection, and CD71 depletion followed by α6-integrin positive selection. The results of flow cytometry analysis showed that all four strategies had ideal effects. Specifically, we conducted a series of researches on HfSCs characterized by their high level of CD34, termed CD34bri cells, and low to undetectable expression of CD34, termed CD34dim cells. CD34bri cells had greater proliferative potential and higher colony-forming ability than CD34dim cells. Furthermore, CD34bri cells had some typical characteristics as progenitor cells, such as large nucleus, obvious nucleolus, large nuclear:cytoplasmic ratio and few cytoplasmic organelles. Our findings clearly demonstrated that HfSCs with high purity and viability could be successfully enriched with Vario MACS

  2. Auditory Efferent System Modulates Mosquito Hearing.

    Science.gov (United States)

    Andrés, Marta; Seifert, Marvin; Spalthoff, Christian; Warren, Ben; Weiss, Lukas; Giraldo, Diego; Winkler, Margret; Pauls, Stephanie; Göpfert, Martin C

    2016-08-01

    The performance of vertebrate ears is controlled by auditory efferents that originate in the brain and innervate the ear, synapsing onto hair cell somata and auditory afferent fibers [1-3]. Efferent activity can provide protection from noise and facilitate the detection and discrimination of sound by modulating mechanical amplification by hair cells and transmitter release as well as auditory afferent action potential firing [1-3]. Insect auditory organs are thought to lack efferent control [4-7], but when we inspected mosquito ears, we obtained evidence for its existence. Antibodies against synaptic proteins recognized rows of bouton-like puncta running along the dendrites and axons of mosquito auditory sensory neurons. Electron microscopy identified synaptic and non-synaptic sites of vesicle release, and some of the innervating fibers co-labeled with somata in the CNS. Octopamine, GABA, and serotonin were identified as efferent neurotransmitters or neuromodulators that affect auditory frequency tuning, mechanical amplification, and sound-evoked potentials. Mosquito brains thus modulate mosquito ears, extending the use of auditory efferent systems from vertebrates to invertebrates and adding new levels of complexity to mosquito sound detection and communication. PMID:27476597

  3. The mechanism of pneumolysin-induced cochlear hair cell death in the rat.

    Science.gov (United States)

    Beurg, Maryline; Hafidi, Aziz; Skinner, Liam; Cowan, Graeme; Hondarrague, Yannick; Mitchell, Tim J; Dulon, Didier

    2005-10-01

    Streptoccocus pneumoniae infection can result in local and systemic diseases such as otitis media, pneumonia and meningitis. Sensorineural hearing loss associated with this infection is mediated by the release of an exotoxin, pneumolysin. The goal of the present study was to characterize the mechanisms of pneumolysin toxicity in cochlear hair cells in vitro. Pneumolysin induced severe damage in cochlear hair cells, ranging from stereocilia disorganization to total cell loss. Surprisingly, pneumolysin-induced cell death preferentially targeted inner hair cells. Pneumolysin triggered in vitro cell death by an influx of calcium. Extracellular calcium appeared to enter the cell through a pore formed by the toxin. Buffering intracellular calcium with BAPTA improved hair cell survival. The mitochondrial apoptotic pathway involved in pneumolysin-induced cell death was demonstrated by the use of bongkrekic acid. Binding of pneumolysin to the hair cell plasma membrane was required to induce cell death. Increasing external calcium reduced cell toxicity by preventing the binding of pneumolysin to hair cell membranes. These results showed the significant role of calcium both in triggering pneumolysin-induced hair cell apoptosis and in preventing the toxin from binding to its cellular target. PMID:16051626

  4. Cockayne Syndrome Group B (Csb) and Group A (Csa) Deficiencies Predispose to Hearing Loss and Cochlear Hair Cell Degeneration in Mice

    Science.gov (United States)

    Nagtegaal, A. Paul; Rainey, Robert N.; van der Pluijm, Ingrid; Brandt, Renata M.C.; van der Horst, Gijsbertus T.J.

    2015-01-01

    Sensory hair cells in the cochlea, like most neuronal populations that are postmitotic, terminally differentiated, and non-regenerating, depend on robust mechanisms of self-renewal for lifelong survival. We report that hair cell homeostasis requires a specific sub-branch of the DNA damage nucleotide excision repair pathway, termed transcription-coupled repair (TCR). Cockayne syndrome (CS), caused by defects in TCR, is a rare DNA repair disorder with a broad clinical spectrum that includes sensorineural hearing loss. We tested hearing and analyzed the cellular integrity of the organ of Corti in two mouse models of this disease with mutations in the Csb gene (CSBm/m mice) and Csa gene (Csa−/− mice), respectively. Csbm/m and Csa−/− mice manifested progressive hearing loss, as measured by an increase in auditory brainstem response thresholds. In contrast to wild-type mice, mutant mice showed reduced or absent otoacoustic emissions, suggesting cochlear outer hair cell impairment. Hearing loss in Csbm/m and Csa−/− mice correlated with progressive hair cell loss in the base of the organ of Corti, starting between 6 and 13 weeks of age, which increased by 16 weeks of age in a basal-to-apical gradient, with outer hair cells more severely affected than inner hair cells. Our data indicate that the hearing loss observed in CS patients is reproduced in mouse models of this disease. We hypothesize that accumulating DNA damage, secondary to the loss of TCR, contributes to susceptibility to hearing loss. PMID:25762674

  5. Natural bizbenzoquinoline derivatives protect zebrafish lateral line sensory hair cells from aminoglycoside toxicity

    Directory of Open Access Journals (Sweden)

    Matthew eKruger

    2016-03-01

    Full Text Available Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment.

  6. Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes

    NARCIS (Netherlands)

    Kawashima, Yoshiyuki; Geleoc, Gwenaelle S. G.; Kurima, Kiyoto; Labay, Valentina; Lelli, Andrea; Asai, Yukako; Makishima, Tomoko; Wu, Doris K.; Della Santina, Charles C.; Holt, Jeffrey R.; Griffith, Andrew J.

    2011-01-01

    Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in

  7. Biotechnology in the Treatment of Sensorineural Hearing Loss: Foundations and Future of Hair Cell Regeneration

    Science.gov (United States)

    Parker, Mark A.

    2011-01-01

    Purpose: To provide an overview of the methodologies involved in the field of hair cell regeneration. First, the author provides a tutorial on the biotechnological foundations of this field to assist the reader in the comprehension and interpretation of the research involved in hair cell regeneration. Next, the author presents a review of stem…

  8. Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity.

    Science.gov (United States)

    Kruger, Matthew; Boney, Robert; Ordoobadi, Alexander J; Sommers, Thomas F; Trapani, Josef G; Coffin, Allison B

    2016-01-01

    Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment. PMID:27065807

  9. Reinnervation of hair cells by neural stem cell-derived neurons

    Institute of Scientific and Technical Information of China (English)

    Yuan Yasheng; Wang Yang; Chi Fanglu

    2014-01-01

    Background Replacement of spiral ganglion neurons would be one prioritized step in an attempt to restore sensory neuronal hearing loss.However,the possibility that transplanted neurons could regenerate new synaptic connections to hair cells has not been explored.The objective of this study was to test whether neural stem cell (NSC)-derived neurons can form synaptic connections with hair cells in vitro.Methods NSCs were mechanically separated from the hippocampus in SD rat embryos (E12-E14) and cultured in a serum-free medium containing basic fibroblast growth factor and epidermal growth factor.Rat NSCs were co-cultured with explants of cochlea sensory epithelia obtained from postnatal Day 3 rats under transway filter membrane.Results At Day 3,the NSCs began to show chemotactic differentiation and grew toward cochlea sensory epithelia.After 9-day co-culture,neurites of NSC-derived neurons predominantly elongated toward hair cells.Immunohistochemical analyses revealed the fibers overlapped with synapsin and hair cells,indicating the formation of new synaptic connections.After 14-day culture,triple staining revealed the fibers overlapped with PSD95 (postsynaptic density) which is juxtaposed with CtBP2 (presynaptic vesicle),indicating the formation of new ribbon synapse.Conclusions NSC-derived neurons can make synaptic connections with hair cells and provide a model for studying synaptic plasticity and regeneration.Whether the newly forming synapse is functional merits further electrophysiological study.

  10. Cell wall-associated ROOT HAIR SPECIFIC 10, a proline-rich receptor-like kinase, is a negative modulator of Arabidopsis root hair growth.

    Science.gov (United States)

    Hwang, Youra; Lee, Hyodong; Lee, Young-Sook; Cho, Hyung-Taeg

    2016-04-01

    Plant cell growth is restricted by the cell wall, and cell wall dynamics act as signals for the cytoplasmic and nuclear events of cell growth. Among various receptor kinases, ROOT HAIR SPECIFIC 10 (RHS10) belongs to a poorly known receptor kinase subfamily with a proline-rich extracellular domain. Here, we report that RHS10 defines the root hair length of Arabidopsis thaliana by negatively regulating hair growth. RHS10 modulates the duration of root hair growth rather than the growth rate. As poplar and rice RHS10 orthologs also showed a root hair-inhibitory function, this receptor kinase-mediated function appears to be conserved in angiosperms. RHS10 showed a strong association with the cell wall, most probably through its extracellular proline-rich domain (ECD). Deletion analysis of the ECD demonstrated that a minimal extracellular part, which includes a few proline residues, is required for RHS10-mediated root hair inhibition. RHS10 suppressed the accumulation of reactive oxygen species (ROS) in the root, which are necessary for root hair growth. A yeast two-hybrid screening identified an RNase (RNS2) as a putative downstream target of RHS10. Accordingly, RHS10 overexpression decreased and RHS10 loss increased RNA levels in the hair-growing root region. Our results suggest that RHS10 mediates cell wall-associated signals to maintain proper root hair length, at least in part by regulating RNA catabolism and ROS accumulation. PMID:26884603

  11. Activating β-catenin signaling in CD133-positive dermal papilla cells increases hair inductivity.

    Science.gov (United States)

    Zhou, Linli; Yang, Kun; Xu, Mingang; Andl, Thomas; Millar, Sarah E; Boyce, Steven; Zhang, Yuhang

    2016-08-01

    Bioengineering hair follicles using cells isolated from human tissue remains a difficult task. Dermal papilla (DP) cells are known to guide the growth and cycling activities of hair follicles by interacting with keratinocytes. However, DP cells quickly lose their inductivity during in vitro passaging. Rodent DP cell cultures need external addition of growth factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a subpopulation of DP cells that are capable of inducing hair follicle formation in vivo. We report here that expression of a stabilized form of β-catenin promoted clonal growth of CD133-positive (CD133+) DP cells in in vitro three-dimensional hydrogel culture while maintaining expression of DP markers, including alkaline phosphatase (AP), CD133, and integrin α8. After a 2-week in vitro culture, cultured CD133+ DP cells with up-regulated β-catenin activity led to an accelerated in vivo hair growth in reconstituted skin compared to control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was up-regulated in CD133+ DP cells. Our data highlight an important role for β-catenin signaling in promoting the inductive capability of CD133+ DP cells for in vitro expansion and in vivo hair follicle regeneration, which could potentially be applied to cultured human DP cells. PMID:27312243

  12. Gene Therapy Restores Hair Cell Stereocilia Morphology in Inner Ears of Deaf Whirler Mice.

    Science.gov (United States)

    Chien, Wade W; Isgrig, Kevin; Roy, Soumen; Belyantseva, Inna A; Drummond, Meghan C; May, Lindsey A; Fitzgerald, Tracy S; Friedman, Thomas B; Cunningham, Lisa L

    2016-02-01

    Hereditary deafness is one of the most common disabilities affecting newborns. Many forms of hereditary deafness are caused by morphological defects of the stereocilia bundles on the apical surfaces of inner ear hair cells, which are responsible for sound detection. We explored the effectiveness of gene therapy in restoring the hair cell stereocilia architecture in the whirlin mouse model of human deafness, which is deaf due to dysmorphic, short stereocilia. Wild-type whirlin cDNA was delivered via adeno-associated virus (AAV8) by injection through the round window of the cochleas in neonatal whirler mice. Subsequently, whirlin expression was detected in infected hair cells (IHCs), and normal stereocilia length and bundle architecture were restored. Whirlin gene therapy also increased inner hair cell survival in the treated ears compared to the contralateral nontreated ears. These results indicate that a form of inherited deafness due to structural defects in cochlear hair cells is amenable to restoration through gene therapy. PMID:26307667

  13. Spatial Distribution of Stem Cell-Like Keratinocytes in Dissected Compound Hair Follicles of the Dog.

    Directory of Open Access Journals (Sweden)

    Dominique J Wiener

    Full Text Available Hair cycle disturbances are common in dogs and comparable to some alopecic disorders in humans. A normal hair cycle is maintained by follicular stem cells which are predominately found in an area known as the bulge. Due to similar morphological characteristics of the bulge area in humans and dogs, the shared particularity of compound hair follicles as well as similarities in follicular biomarker expression, the dog is a promising model to study human hair cycle and stem cell disorders. To gain insight into the spatial distribution of follicular keratinocytes with stem cell potential in canine compound follicles, we microdissected hair follicles in anagen and telogen from skin samples of freshly euthanized dogs. The keratinocytes isolated from different locations were investigated for their colony forming efficiency, growth and differentiation potential as well as clonal growth. Our results indicate that i compound and single hair follicles exhibit a comparable spatial distribution pattern with respect to cells with high growth potential and stem cell-like characteristics, ii the lower isthmus (comprising the bulge harbors most cells with high growth potential in both, the anagen and the telogen hair cycle stage, iii unlike in other species, colonies with highest growth potential are rather small with an irregular perimeter and iv the keratinocytes derived from the bulbar region exhibit characteristics of actively dividing transit amplifying cells. Our results now provide the basis to conduct comparative studies of normal dogs and those with hair cycle disorders with the possibility to extend relevant findings to human patients.

  14. Epidermal stem cells and skin tissue engineering in hair follicle regeneration

    OpenAIRE

    Balañá, María Eugenia; Charreau, Hernán Eduardo; Leirós, Gustavo José

    2015-01-01

    The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge still pending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients’ psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair folli...

  15. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves

    OpenAIRE

    Amoh, Yasuyuki; Li, Lingna; Campillo, Raul; Kawahara, Katsumasa; Katsuoka, Kensei; Penman, Sheldon; Robert M Hoffman

    2005-01-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but ne...

  16. Energy output from a single outer hair cell

    CERN Document Server

    Iwasa, Kuni H

    2016-01-01

    Electromotility of outer hair cells (OHCs) has been extensively studied with in vitro experiments because of its physiological significance in the cochlear amplifier, which provides the exquisite sensitivity and frequency selectivity of the mammalian ear. However, these studies have been performed largely under load-free conditions or with static load, while these cells function in vivo in a dynamic environment, receiving electrical energy to enhance mechanical oscillation in the inner ear. This gap leaves uncertainties in addressing a key issue, how much mechanical energy an OHC provides. The present report is an attempt of bridging the gap by introducing a simple one-dimensional model for electromotility of OHC in a dynamic environment. This model incorporates a feedback loop involving the receptor potential and the mechanical load on OHC, and leads to an analytical expression for the membrane capacitance, which explicitly describes the dependence on the elastic load, viscous drag, and the mass. The derived...

  17. Hair & skin derived progenitor cells: In search of a candidate cell for regenerative medicine

    Science.gov (United States)

    Kumar, Anil; Mohanty, Sujata; Nandy, Sushmita Bose; Gupta, Somesh; Khaitan, Binod K.; Sharma, Shilpa; Bhargava, Balram; Airan, Balram

    2016-01-01

    Background & objectives: Skin is an established tissue source for cell based therapy. The hair follicle has been introduced later as a tissue source for cell based therapy. The ease of tissue harvest and multipotent nature of the resident stem cells in skin and hair follicle has promoted basic and clinical research in this area. This study was conducted to evaluate skin stem cells (SSCs) and hair follicle stem cells (HFSCs) as candidate cells appropriate for neuronal and melanocyte lineage differentiation. Methods: In this study, SSCs and hair follicle stem cells (HFSCs) were expanded in vitro by explant culture method and were compared in terms of proliferative potential and stemness; differentiation potential into melanocytes and neuronal lineage. Results: SSCs were found to be more proliferative in comparison to HFSCs, however, telomerase activity was more in HFSCs in comparison to SSCs. Capacity to differentiate into two lineages of ectoderm origin (neuronal and melanocyte) was found to be different. HFSCs cells showed more propensities towards melanocyte lineage, whereas SSCs were more inclined towards neuronal lineage. Interpretation & conclusions: The study showed that SSCs had differential advantage over the HFSCs for neuronal cell differentiation, whereas, the HFSCs were better source for melanocytic differentiation. PMID:27121515

  18. Distinct roles of Eps8 in the maturation of cochlear and vestibular hair cells.

    Science.gov (United States)

    Tavazzani, Elisa; Spaiardi, Paolo; Zampini, Valeria; Contini, Donatella; Manca, Marco; Russo, Giancarlo; Prigioni, Ivo; Marcotti, Walter; Masetto, Sergio

    2016-07-22

    Several genetic mutations affecting the development and function of mammalian hair cells have been shown to cause deafness but not vestibular defects, most likely because vestibular deficits are sometimes centrally compensated. The study of hair cell physiology is thus a powerful direct approach to ascertain the functional status of the vestibular end organs. Deletion of Epidermal growth factor receptor pathway substrate 8 (Eps8), a gene involved in actin remodeling, has been shown to cause deafness in mice. While both inner and outer hair cells from Eps8 knockout (KO) mice showed abnormally short stereocilia, inner hair cells (IHCs) also failed to acquire mature-type ion channels. Despite the fact that Eps8 is also expressed in vestibular hair cells, Eps8 KO mice show no vestibular deficits. In the present study we have investigated the properties of vestibular Type I and Type II hair cells in Eps8-KO mice and compared them to those of cochlear IHCs. In the absence of Eps8, vestibular hair cells show normally long kinocilia, significantly shorter stereocilia and a normal pattern of basolateral voltage-dependent ion channels. We have also found that while vestibular hair cells from Eps8 KO mice show normal voltage responses to injected sinusoidal currents, which were used to mimic the mechanoelectrical transducer current, IHCs lose their ability to synchronize their responses to the stimulus. We conclude that the absence of Eps8 produces a weaker phenotype in vestibular hair cells compared to cochlear IHCs, since it affects the hair bundle morphology but not the basolateral membrane currents. This difference is likely to explain the absence of obvious vestibular dysfunction in Eps8 KO mice. PMID:27132230

  19. Laser selective microablation of sensitized intracellular components within auditory receptor cells

    Science.gov (United States)

    Harris, David M.; Evans, Burt N.; Santos-Sacchi, Joseph

    1995-05-01

    A laser system can be coupled to a light microscope for laser microbeam ablation and trapping of single cells in vitro. We have extended this technology by sensitization of target structures with vital dyes to provide selective ablation of specific subcellular components. Isolated auditory receptor cells (outer hair cells, OHCs) are known to elongate and contract in response to electrical, chemical and mechanical stimulation. Various intracellular structures are candidate components mediating motility of OHCs, but the exact mechanism(s) is currently unknown. In ongoing studies of OHC motility, we have used the microbeam for selective ablation of lateral wall components and of an axial cytoskeletal core that extends from the nucleus to the cell apex. Both the area beneath the subsurface cistemae of the lateral wall and the core are rich in mitochondria. OHCs isolated from guinea pig cochlea are suspended in L- 15 medium containing 2.0 (mu) M Rhodamine 123, a porphyrin with an affinity for mitochondria. A spark-pumped nitrogen laser pumping a dye cell (Coumarin 500) was aligned on the optical axis of a Nikon Optiphot-2 to produce a 3 ns, 0.5 - 10 micrometers spot (diameter above ablation threshold w/50X water immersion, N.A. 0.8), and energy at the target approximately equals 10 (mu) J/pulse. At short incubation times in Rh123 irradiation caused local blebbing or bulging of cytoplastic membrane and thus loss of the OHC's cylindrical shape. At longer Rh123 incubation times when the central axis of the cell was targeted we observed cytoplasmic clearing, immediate cell elongation (approximately equals 5%) and clumping of core material at nuclear and apical attachments. Experiments are underway to examine the significance of these preliminary observations.

  20. FM dye photo-oxidation as a tool for monitoring membrane recycling in inner hair cells.

    Directory of Open Access Journals (Sweden)

    Dirk Kamin

    Full Text Available Styryl (FM dyes have been used for more than two decades to investigate exo- and endocytosis in conventional synapses. However, they are difficult to use in the inner hair cells of the auditory pathway (IHCs, as FM dyes appear to penetrate through mechanotransducer channels into the cytosol of IHCs, masking endocytotic uptake. To solve this problem we applied to IHCs the FM dye photo-oxidation technique, which renders the dyes into electron microscopy markers. Photo-oxidation allowed the unambiguous identification of labeled organelles, despite the presence of FM dye in the cytosol. This enabled us to describe the morphologies of several organelles that take up membrane in IHCs, both at rest and during stimulation. At rest, endosome-like organelles were detected in the region of the cuticular plate. Larger tubulo-cisternal organelles dominated the top and nuclear regions. Finally, the basal region, where the IHC active zones are located, contained few labeled organelles. Stimulation increased significantly membrane trafficking in the basal region, inducing the appearance of labeled vesicles and cistern-like organelles. The latter were replaced by small, synaptic-like vesicles during recovery after stimulation. In contrast, no changes in membrane trafficking were induced by stimulation in the cuticular plate region or in the top and nuclear regions. We conclude that synaptic vesicle recycling takes place mostly in the basal region of the IHCs. Other organelles participate in abundant constitutive membrane trafficking throughout the rest of the IHC volume.

  1. All Three Rows of Outer Hair Cells Are Required for Cochlear Amplification

    Directory of Open Access Journals (Sweden)

    Michio Murakoshi

    2015-01-01

    Full Text Available In the mammalian auditory system, the three rows of outer hair cells (OHCs located in the cochlea are thought to increase the displacement amplitude of the organ of Corti. This cochlear amplification is thought to contribute to the high sensitivity, wide dynamic range, and sharp frequency selectivity of the hearing system. Recent studies have shown that traumatic stimuli, such as noise exposure and ototoxic acid, cause functional loss of OHCs in one, two, or all three rows. However, the degree of decrease in cochlear amplification caused by such functional losses remains unclear. In the present study, a finite element model of a cross section of the gerbil cochlea was constructed. Then, to determine effects of the functional losses of OHCs on the cochlear amplification, changes in the displacement amplitude of the basilar membrane (BM due to the functional losses of OHCs were calculated. Results showed that the displacement amplitude of the BM decreases significantly when a single row of OHCs lost its function, suggesting that all three rows of OHCs are required for cochlear amplification.

  2. The potential of stem cells for the restoration of auditory function in humans

    OpenAIRE

    Hu, Zhengqing; Ulfendahl, Mats

    2013-01-01

    Hearing loss is one of the most common disabilities, affecting approximately 10% of the population. Hair cells and spiral ganglion neurons are usually damaged in most cases of hearing loss. Currently, there is virtually no biological approach to replace damaged hearing cells. Recent developments in stem cell technology provide new opportunities for the treatment of deafness. Two major strategies have been investigated: differentiation of endogenous stem cells into new hair cells; and introduc...

  3. Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition.

    Science.gov (United States)

    Taura, A; Taura, K; Koyama, Y; Yamamoto, N; Nakagawa, T; Ito, J; Ryan, A F

    2016-05-01

    Once inner ear hair cells (HCs) are damaged by drugs, noise or aging, their apical structures including the stereociliary arrays are frequently the first cellular feature to be lost. Although this can be followed by progressive loss of HC somata, a significant number of HC bodies often remain even after stereociliary loss. However, in the absence of stereocilia they are nonfunctional. HCs can sometimes be regenerated by Atoh1 transduction or Notch inhibition, but they also may lack stereociliary bundles. It is therefore important to develop methods for the regeneration of stereocilia, in order to achieve HC functional recovery. Espin is an actin-bundling protein known to participate in sterociliary elongation during development. We evaluated stereociliary array regeneration in damaged vestibular sensory epithelia in tissue culture, using viral vector transduction of two espin isoforms. Utricular HCs were damaged with aminoglycosides. The utricles were then treated with a γ-secretase inhibitor, followed by espin or control transduction and histochemistry. Although γ-secretase inhibition increased the number of HCs, few had stereociliary arrays. In contrast, 46 h after espin1 transduction, a significant increase in hair-bundle-like structures was observed. These were confirmed to be immature stereociliary arrays by scanning electron microscopy. Increased uptake of FM1-43 uptake provided evidence of stereociliary function. Espin4 transduction had no effect. The results demonstrate that espin1 gene therapy can restore stereocilia on damaged or regenerated HCs. PMID:26886463

  4. Development of K+ and Na+ conductances in rodent postnatal semicircular canal type I hair cells

    OpenAIRE

    Li, Gang Q.; Meredith, Frances L.; Rennie, Katherine J.

    2009-01-01

    The rodent vestibular system is immature at birth. During the first postnatal week, vestibular type I and type II hair cells start to acquire their characteristic morphology and afferent innervation. We have studied postnatal changes in the membrane properties of type I hair cells acutely isolated from the semicircular canals (SCC) of gerbils and rats using whole cell patch clamp and report for the first time developmental changes in ionic conductances in these cells. At postnatal day (P) 5 i...

  5. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration

    OpenAIRE

    Plikus, M. V.; Mayer, J. A.; de La Cruz, D.; Baker, Ruth E.; Maini, P.K.; Maxson, R.; Chuong, C M

    2008-01-01

    In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life1, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge2 are regulated by the surrounding microenvironment, or niche3. The activation of such stem cells is cyclic, involving periodic -catenin activity4, 5, 6, 7. In the adult mouse, regeneration occurs in ...

  6. Auditory and non-auditory effects of noise on health.

    Science.gov (United States)

    Basner, Mathias; Babisch, Wolfgang; Davis, Adrian; Brink, Mark; Clark, Charlotte; Janssen, Sabine; Stansfeld, Stephen

    2014-04-12

    Noise is pervasive in everyday life and can cause both auditory and non-auditory health effects. Noise-induced hearing loss remains highly prevalent in occupational settings, and is increasingly caused by social noise exposure (eg, through personal music players). Our understanding of molecular mechanisms involved in noise-induced hair-cell and nerve damage has substantially increased, and preventive and therapeutic drugs will probably become available within 10 years. Evidence of the non-auditory effects of environmental noise exposure on public health is growing. Observational and experimental studies have shown that noise exposure leads to annoyance, disturbs sleep and causes daytime sleepiness, affects patient outcomes and staff performance in hospitals, increases the occurrence of hypertension and cardiovascular disease, and impairs cognitive performance in schoolchildren. In this Review, we stress the importance of adequate noise prevention and mitigation strategies for public health. PMID:24183105

  7. Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability

    OpenAIRE

    Lee, Jeong-Han; Park, Channy; Kim, Se-Jin; Kim, Hyung-Jin; Oh, Gi-Su; Shen, Aihua; So, Hong-Seob; Park, Raekil

    2013-01-01

    Hair cells at the base of the cochlea appear to be more susceptible to damage by the aminoglycoside gentamicin than those at the apex. However, the mechanism of base-to-apex gradient ototoxicity by gentamicin remains to be elucidated. We report here that gentamicin caused rodent cochlear hair cell damages in a time- and dose-dependent manner. Hair cells at the basal turn were more vulnerable to gentamicin than those at the apical turn. Gentamicin-conjugated Texas Red (GTTR) uptake was predomi...

  8. Why do hair cells and spiral ganglion neurons in the cochlea die during aging?

    OpenAIRE

    Perez, Philip; Bao, Jianxin

    2011-01-01

    Age-related decline of cochlear function is mainly due to the loss of hair cells and spiral ganglion neurons (SGNs). Recent findings clearly indicate that survival of these two cell types during aging depends on genetic and environmental interactions, and this relationship is seen at the systemic, tissue, cellular, and molecular levels. At cellular and molecular levels, age-related loss of hair cells and SGNs can occur independently, suggesting distinct mechanisms for the death of each during...

  9. A two-step mechanism underlies the planar polarization of regenerating sensory hair cells

    OpenAIRE

    López-Schier, Hernán; Hudspeth, A. J.

    2006-01-01

    The restoration of planar cell polarity is an essential but poorly understood step toward physiological recovery during sensory-organ regeneration. Investigating this issue in the lateral line of the zebrafish, we found that hair cells regenerate in pairs along a single axis established by the restricted localization and oriented division of their progenitors. By analyzing mutants lacking the planar-polarity determinant Vangl2, we ascertained that the uniaxial production of hair cells and the...

  10. The actin Cytoskeleton in Root Hairs: a cell elongation device

    NARCIS (Netherlands)

    Ketelaar, T.; Emons, A.M.C.

    2009-01-01

    The actin cytoskeleton plays an important role in root hair development. It is involved in both the delivery of growth materials to the expanding tip of root hairs and the regulation of the area of tip growth. This review starts with a discussion of the techniques that are available to visualize the

  11. Forward masking in distinguishing inner and outer hair cell damage

    Institute of Scientific and Technical Information of China (English)

    DUAN Mao-li

    2009-01-01

    @@ Forward Masking Temporal audiotory resolution is the ability of the auditory system to resolve auditory signals in the time domain. Forward masking is a means of studying tem-poral resolution where one tone, the probe, is masked by a preceding tone, the masker. Forward masking is believed to relate to the adaptation of the aucliotory system[1-4].

  12. Extracted hair follicle outer root sheath cell suspension for pigment cell restoration in vitiligo

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2013-01-01

    Full Text Available Vitiligo surgery has come up a long way from punch skin grafts to epidermal cell suspension and latest to the extracted hair follicle outer root sheath cell suspension (EHF-ORS-CS transplantation. The progressive development from one technique to the other is always in a quest for the best. In the latest development- EHF-ORS-CS, which is an enriched source of follicular inactive melanocyte (melanocyte stem cells, seems to be a good addition to the prevailing cell-based therapies for vitiligo; however, need to be explored further in larger, and preferably randomized blinded studies. This review discusses the principle, technical details, and stem cell composition of hair follicular outer root sheath cell suspension.

  13. Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-ping; HU Bo-hua; SUN Jian-he; ZHAI Suo-qiang; Donald Henderson

    2010-01-01

    Background Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae.Methods The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy.Results Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs.Conclusions In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.

  14. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  15. Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the anagen hair follicle in canine species

    OpenAIRE

    Gargiulo, A.M.; Pedini, V.; C. Dall’Aglio; Ceccarelli, P.; L. Pascucci; F Mercati

    2009-01-01

    The dermal sheath (DS) of the hair follicle is comprised by fibroblast-like cells and extends along the follicular epithelium, from the bulb up to the infundibulum. From this structure, cells with stem characteristics were isolated: they have a mesenchymal origin and express CD90 protein, a typical marker of mesenchymal stem cells. It is not yet really clear in which region of hair follicle these cells are located but some experimental evidence suggests that dermal stem cells are localized pr...

  16. Hair cell and organ of corti responses to normal and intense acoustic stimulation

    OpenAIRE

    Fridberger, Anders

    1997-01-01

    The principal aims of the studies described in this thesis were to develop an in vitro model for studying acoustic overstimulation at the cellular level, to define the electrical and mechanical response characteristics of the perfused temporal bone preparation, and to investigate the effects of intense sound stimulation on the calcium levels of the hair cells in the intact hearing organ. In the in vitro model for acoustic overstimulation, isolated cochlear outer hair cells ...

  17. P2X antagonists inhibit styryl dye entry into hair cells

    OpenAIRE

    Crumling, Mark A.; Tong, Mingjie; Aschenbach, Krista L.; Liu, Li Qian; Pipitone, Christine M.; Duncan, R Keith

    2009-01-01

    The styryl pyridinium dyes, FM1-43 and AM1-43, are fluorescent molecules that can permeate the mechanotransduction channels of hair cells, the sensory receptors of the inner ear. When these dyes are applied to hair cells, they enter the cytoplasm rapidly, resulting in a readily detectable increase in intracellular fluorescence that is often used as a molecular indication of mechanotransduction channel function. However, such dyes can also permeate the ATP receptor, P2X2. Therefore, we explore...

  18. Ionic mechanisms subserving mechanosensory transduction and neural integration in statocyst hair cells of Hermissenda

    Science.gov (United States)

    Farley, Joseph

    1988-01-01

    The neural processing of gravitational-produced sensory stimulation of statocyst hair cells in the nudibranch mollusk Hermissenda was studied. The goal in these studies was to understand how: gravireceptor neurons sense or transduce gravitational forces, gravitational stimulation is integrated so as to produce a graded receptor potential, and ultimately the generation of an action potential, and various neural adaptation phenomena which hair cells exhibit arise. The approach to these problems was primarily electrophysical.

  19. Hair regrowth in alopecia areata patients following Stem Cell Educator therapy

    OpenAIRE

    Li, Yanjia; Yan, Baoyong; Wang, Hepeng; Li, Heng; Li, Quanhai; Zhao, Dong; Chen, Yana; Zhang, Ye; Li, Wenxia; Zhang, Jun; Wang, Shanfeng; Shen, Jie; Li, Yunxiang; Guindi, Edward; Zhao, Yong

    2015-01-01

    Background Alopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens. Methods We have developed a Stem Cell Educator therapy in which a patient’s blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allow...

  20. Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding.

    Science.gov (United States)

    Gay, Denise; Kwon, Ohsang; Zhang, Zhikun; Spata, Michelle; Plikus, Maksim V; Holler, Phillip D; Ito, Mayumi; Yang, Zaixin; Treffeisen, Elsa; Kim, Chang D; Nace, Arben; Zhang, Xiaohong; Baratono, Sheena; Wang, Fen; Ornitz, David M; Millar, Sarah E; Cotsarelis, George

    2013-07-01

    Understanding molecular mechanisms for regeneration of hair follicles provides new opportunities for developing treatments for hair loss and other skin disorders. Here we show that fibroblast growth factor 9 (Fgf9), initially secreted by γδ T cells, modulates hair follicle regeneration after wounding the skin of adult mice. Reducing Fgf9 expression decreases this wound-induced hair neogenesis (WIHN). Conversely, overexpression of Fgf9 results in a two- to threefold increase in the number of neogenic hair follicles. We found that Fgf9 from γδ T cells triggers Wnt expression and subsequent Wnt activation in wound fibroblasts. Through a unique feedback mechanism, activated fibroblasts then express Fgf9, thus amplifying Wnt activity throughout the wound dermis during a crucial phase of skin regeneration. Notably, humans lack a robust population of resident dermal γδ T cells, potentially explaining their inability to regenerate hair after wounding. These findings highlight the essential relationship between the immune system and tissue regeneration. The importance of Fgf9 in hair follicle regeneration suggests that it could be used therapeutically in humans. PMID:23727932

  1. Wnt7b is an important intrinsic regulator of hair follicle stem cell homeostasis and hair follicle cycling.

    Science.gov (United States)

    Kandyba, Eve; Kobielak, Krzysztof

    2014-04-01

    The hair follicle (HF) is an exceptional mini-organ to study the mechanisms which regulate HF morphogenesis, cycling, hair follicle stem cell (hfSCs) homeostasis, and progeny differentiation. During morphogenesis, Wnt signaling is well-characterized in the initiation of HF patterning but less is known about which particular Wnt ligands are required and whether individual Wnt ligands act in an indispensable or redundant manner during postnatal hfSCs anagen onset and HF cycle progression. Previously, we described the function of the bone morphogenetic protein (BMP) signaling target gene WNT7a in intrinsic regulation of hfSCs homeostasis in vivo. Here, we investigated the role of Wnt7b, which was also intrinsically upregulated in hfSCs during physiological and precocious anagen after BMP inhibition in vivo. We demonstrated Wnt7b to be a direct target of canonical BMP signaling in hfSCs and using Wnt7b conditional gene targeting during HF morphogenesis revealed disrupted HF cycling including a shorter anagen, premature catagen onset with overall shorter hair production, and diminished HF differentiation marker expression. Additionally, we observed that postnatal ablation of Wnt7b resulted in delayed HF activation, affecting both the hair germ and bulge hfSCs but still maintaining a two-step sequence of HF stimulation. Interestingly, Wnt7b cKO hfSCs participated in reformation of the new HF bulge, but with slower self-renewal. These findings demonstrate the importance of intrinsic Wnt7b expression in hfSCs regulation and normal HF cycling and surprisingly reveal a nonredundant role for Wnt7b in the control of HF anagen length and catagen entry which was not compensated by other Wnt ligands. PMID:24222445

  2. Distribution and time course of hair cell regeneration in the pigeon utricle

    Science.gov (United States)

    Dye, B. J.; Frank, T. C.; Newlands, S. D.; Dickman, J. D.

    1999-01-01

    Vestibular and cochlear regeneration following ototoxic insult from aminoglycoside antibiotics has been well documented, particularly in birds. In the present study, intraotic application of a 2 mg streptomycin paste was used to achieve complete vestibular hair cell destruction in pigeons (Columba livia) while preserving regenerative ability. Scanning electron microscopy was used to quantify hair cell density longitudinally during regeneration in three different utricular macula locations, including the striola, central and peripheral regions. The utricular epithelium was void of stereocilia (indicating hair cell loss) at 4 days after intraotic treatment with streptomycin. At 2 weeks the stereocilia began to appear randomly and mostly in an immature form. However, when present most kinocilia were polarized toward the developing striola. Initially, regeneration occurred more rapidly in the central and peripheral regions of the utricle as compared to the striola. As regeneration proceeded from 2 to 12 weeks, hair cell density in the striola region equaled the density noted in the central and peripheral regions. At 24 weeks, hair cell density of the central and peripheral regions was equal to normal values, however the striola region had a slightly greater hair cell density than that observed for normal animals.

  3. Channeling your inner ear potassium: K(+) channels in vestibular hair cells.

    Science.gov (United States)

    Meredith, Frances L; Rennie, Katherine J

    2016-08-01

    During development of vestibular hair cells, K(+) conductances are acquired in a specific pattern. Functionally mature vestibular hair cells express different complements of K(+) channels which uniquely shape the hair cell receptor potential and filtering properties. In amniote species, type I hair cells (HCI) have a large input conductance due to a ubiquitous low-voltage-activated K(+) current that activates with slow sigmoidal kinetics at voltages negative to the membrane resting potential. In contrast type II hair cells (HCII) from mammalian and non-mammalian species have voltage-dependent outward K(+) currents that activate rapidly at or above the resting membrane potential and show significant inactivation. A-type, delayed rectifier and calcium-activated K(+) channels contribute to the outward K(+) conductance and are present in varying proportions in HCII. In many species, K(+) currents in HCII in peripheral locations of vestibular epithelia inactivate more than HCII in more central locations. Two types of inward rectifier currents have been described in both HCI and HCII. A rapidly activating K(+)-selective inward rectifier current (IK1, mediated by Kir2.1 channels) predominates in HCII in peripheral zones, whereas a slower mixed cation inward rectifier current (Ih), shows greater expression in HCII in central zones of vestibular epithelia. The implications for sensory coding of vestibular signals by different types of hair cells are discussed. This article is part of a Special Issue entitled . PMID:26836968

  4. Neuroglobin Expression in the Mammalian Auditory System.

    Science.gov (United States)

    Reuss, Stefan; Banica, Ovidiu; Elgurt, Mirra; Mitz, Stephanie; Disque-Kaiser, Ursula; Riemann, Randolf; Hill, Marco; Jaquish, Dawn V; Koehrn, Fred J; Burmester, Thorsten; Hankeln, Thomas; Woolf, Nigel K

    2016-04-01

    The energy-yielding pathways that provide the large amounts of metabolic energy required by inner ear sensorineural cells are poorly understood. Neuroglobin (Ngb) is a neuron-specific hemoprotein of the globin family, which is suggested to be involved in oxidative energy metabolism. Here, we present quantitative real-time reverse transcription PCR, in situ hybridization, immunohistochemical, and Western blot evidence that neuroglobin is highly expressed in the mouse and rat cochlea. For primary cochlea neurons, Ngb expression is limited to the subpopulation of type I spiral ganglion cells, those which innervate inner hair cells, while the subpopulation of type II spiral ganglion cells which innervate the outer hair cells do not express Ngb. We further investigated Ngb distribution in rat, mouse, and human auditory brainstem centers, and found that the cochlear nuclei and superior olivary complex (SOC) also express considerable amounts of Ngb. Notably, the majority of olivocochlear neurons, those which provide efferent innervation of outer hair cells as identified by neuronal tract tracing, were Ngb-immunoreactive. We also observed that neuroglobin in the SOC frequently co-localized with neuronal nitric oxide synthase, the enzyme responsible for nitric oxide production. Our findings suggest that neuroglobin is well positioned to play an important physiologic role in the oxygen homeostasis of the peripheral and central auditory nervous system, and provides the first evidence that Ngb signal differentiates the central projections of the inner and outer hair cells. PMID:25636685

  5. From embryonic stem cells to sensory hair cells : a programming approach

    OpenAIRE

    Costa, Aida Isabel Santos, 1984-

    2014-01-01

    Tese de doutoramento, Ciências Biomédicas (Biologia do Desenvolvimento), Universidade de Lisboa, Faculdade de Medicina, 2014 It is estimated that 10% of the world population suffers from hearing impairment, and this number tends to rise with the increase in noise pollution and growth of aging population. The most frequent cause is irreversible damage to sensory hair cells (HCs) of the inner ear, which are highly specialized mechanoreceptor cells able to respond to acoustic signals. Non-mam...

  6. Genetically Induced Cell Death in Bulge Stem Cells Reveals Their Redundancy for Hair and Epidermal Regeneration

    OpenAIRE

    Driskell, Iwona; Oeztuerk-Winder, Feride; Humphreys, Peter; Frye, Michaela

    2014-01-01

    Adult mammalian epidermis contains multiple stem cell populations in which quiescent and more proliferative stem and progenitor populations coexist. However, the precise interrelation of these populations in homeostasis remains unclear. Here, we blocked the contribution of quiescent keratin 19 (K19)-expressing bulge stem cells to hair follicle formation through genetic ablation of the essential histone methyltransferase Setd8 that is required for the maintenance of adult skin. Deletion of Set...

  7. Amplification in the auditory periphery: The effect of coupling tuning mechanisms

    Science.gov (United States)

    Montgomery, K. A.; Silber, M.; Solla, S. A.

    2007-05-01

    A mathematical model describing the coupling between two independent amplification mechanisms in auditory hair cells is proposed and analyzed. Hair cells are cells in the inner ear responsible for translating sound-induced mechanical stimuli into an electrical signal that can then be recorded by the auditory nerve. In nonmammals, two separate mechanisms have been postulated to contribute to the amplification and tuning properties of the hair cells. Models of each of these mechanisms have been shown to be poised near a Hopf bifurcation. Through a weakly nonlinear analysis that assumes weak periodic forcing, weak damping, and weak coupling, the physiologically based models of the two mechanisms are reduced to a system of two coupled amplitude equations describing the resonant response. The predictions that follow from an analysis of the reduced equations, as well as performance benefits due to the coupling of the two mechanisms, are discussed and compared with published experimental auditory nerve data.

  8. Distribution of Prestin on Outer Hair Cell Basolateral Surface

    Institute of Scientific and Technical Information of China (English)

    YU Ning; ZHAI Suo-qiang; YANG Shi-ming; HAN Dong-yi; ZHAO Hong-bo

    2008-01-01

    Prestin has been identified as a motor protein responsible for outer hair cell (OHC) electromotility and is expressed on the OHC surface. Previous studies revealed that OHC eleetromotility and its associated nonlinear capacitance were mainly located at the OHC lateral wall and absent at the apical cutieular plate and the basal nucleus region. Immunofluorescent staining for prestin also failed to demonstrate prestin expression at the OHC basal ends in whole-mount preparation of the organ of Corti. However, there lacks a definitive demonstration of the pattern of prestin distribution. The OHC lateral wall has a trilaminate organization and is composed of the plasma membrane, cortical lattice, and subsurface cisternae. In this study, the location of prestin proteins in dissociated OHCs was examined using immunofluorescent staining and confocal microscopy. We found that prestin was uniformly expressed on the basolateral surface, including the basal pole. No staining was seen on the cuticular plate and stereocilia. When co-stained with a membrane marker di-8-ANEPPS, prestin-labeling was found to be in the outer layer of the OHC lateral wall. After separating the plasma membrane from the underlying subsurface eisternae using a hypotonic extracellular solution, prestin-labeling was found to be in the plasma membrane, not the subsurface cisternae. The data show that prestin is expressed in the plasma membrane on the entire OHC basolateral surface.

  9. Making sense of Wnt signaling – linking hair cell regeneration to development

    Directory of Open Access Journals (Sweden)

    Lina eJansson

    2015-03-01

    Full Text Available Wnt signaling is a highly conserved pathway crucial for development and homeostasis of multicellular organisms. Secreted Wnt ligands bind Frizzled receptors to regulate diverse processes such as axis patterning, cell division, and cell fate specification. They also serve to govern self-renewal of somatic stem cells in several adult tissues. The complexity of the pathway can be attributed to the myriad of Wnt and Frizzled combinations as well as its diverse context-dependent functions. In the developing mouse inner ear, Wnt signaling plays diverse roles, including specification of the otic placode and patterning of the otic vesicle. At later stages, its activity governs sensory hair cell specification, cell cycle regulation, and hair cell orientation. In regenerating sensory organs from non-mammalian species, Wnt signaling can also regulate the extent of proliferative hair cell regeneration. This review describes the current knowledge of the roles of Wnt signaling and Wnt-responsive cells in hair cell development and regeneration. We also discuss possible future directions and the potential application and limitation of Wnt signaling in augmenting hair cell regeneration.

  10. Antigen presenting cells in the skin of a patient with hair loss and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2009-09-01

    Full Text Available Context: Hair loss is one of the most striking clinical features of active systemic lupus erythematosus (SLE, however, very few studies have investigated the immunological features of this process. Case report: We describe a 33 years old female who presented with scalp hair loss and arthralgias. Physical examination revealed erythematous plaques on the nose and scalp, with bitemporal hair loss. Scalp biopsies revealed epidermal hyperkeratosis, with a mild interface infiltrate of lymphocytes and histiocytes and a superficial and deep, perivascular and periadnexal infiltrate of mostly CD4 positive cells. Antibodies to HAM 56, CD68, CD1a, S-100, mast cell tryptase and c-kit/CD117 were strongly positive around the hair follicles, and in the adjacent sebaceous glands. Conclusion: We present the first report showing a significant presence of several antigen presenting cells around the hair follicular units in a patient with alopecia in active SLE. Today, antigen presenting cells and dendritic cells (DC are modeled as the master regulators of human immunity. One aspect that has become clearly appreciated is the great diversity of DC subtypes, each with considerable functional differences. Thus, we suggest that APC and DCs are equipped with Pattern Recognition Receptors (PRRs to some hair follicular unit antigens; that these innate sensors recognize conserved molecular patterns on self- tissue, and play a significant role in the pathophysiology of alopecia in SLE patients.

  11. Antigen presenting cells in the skin of a patient with hair loss and systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2009-01-01

    Full Text Available Context: Hair loss is one of the most striking clinical features of active systemic lupus erythematosus (SLE, however, very few studies have investigated the immunological features of this process. Case report: We describe a 33 years old female who presented with scalp hair loss and arthralgias. Physical examination revealed erythematous plaques on the nose and scalp, with bitemporal hair loss. Scalp biopsies revealed epidermal hyperkeratosis, with a mild interface infiltrate of lymphocytes and histiocytes and a superficial and deep, perivascular and periadnexal infiltrate of mostly CD4 positive cells. Antibodies to HAM 56, CD68, CD1a, S-100, mast cell tryptase and c-kit/CD117 were strongly positive around the hair follicles, and in the adjacent sebaceous glands. Conclusion : We present the first report showing a significant presence of several antigen presenting cells around the hair follicular units in a patient with alopecia in active SLE. Today, antigen presenting cells and dendritic cells (DC are modeled as the master regulators of human immunity. One aspect that has become clearly appreciated is the great diversity of DC subtypes, each with considerable functional differences. Thus, we suggest that APC and DCs are equipped with Pattern Recognition Receptors (PRRs to some hair follicular unit antigens; that these innate sensors recognize conserved molecular patterns on self- tissue, and play a significant role in the pathophysiology of alopecia in SLE patients

  12. Retrovirus-Mediated Gene Transfer in Immortalization of Progenitor Hair Cell Lines in Newborn Rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yuan; ZHAI Suo-qiang; SONG Wei; GUO Wei; ZHENG Gui-liang; HU Yin-yan

    2008-01-01

    Objective To present an experimental method that allows isolation of greater epithelial ridge (GER) and lesser epithelial ridge(LER) cells from postnatal rat cochleae using a combinatorial approach of enzymatic digestion and mechanical separation and to investigate a retrovirus-mediated gene transfer technique for its possibl utility in immortalization of the GER and LER cell lines, in an effort to establish an in vitro model system of hair cell differentiation. Methods GER and LER cells were dissected from postnatal rat cochleae and immortalized by transferring the SV40 large T antigen using a retrovirus. The established cell lines were confirmed through morphology observation, immunnocytochemical staining and RT-PCR analysis. The Hathl gene was transferred into the cell lines using adenovirus-mediated techniques to explore their potential to differentiate into hair cells. Results The established cell lines were stably maintained for more than 20 passages and displayed many features similar to primary GER and LER cells. They grew in patches and assumed a polygonal morphology. Immunostaining showed labeling by SV40 large T antigen and Islet1 (a specific marker for GER and LER). All passages of the cell lines expressed SV40 large T antigen on RT-PCR analysis. The cells also showed the capability to differenti-ate into hair cell-like cells when forced to express Hathl. Conclusion Retrovirus-mediated gene transfer can be used in establishing immortalized progenitor hair cell lines in newborn rat, which may provide an invaluable system for studying hair cell differentiation and regeneration for new treatment of sensory hearing loss caused by hair cell loss.

  13. New activators and inhibitors in the hair cycle clock: targeting stem cells' state of competence.

    Science.gov (United States)

    Plikus, Maksim V

    2012-05-01

    The timing mechanism of the hair cycle remains poorly understood. However, it has become increasingly clear that the telogen-to-anagen transition is controlled jointly by at least the bone morphogenic protein (BMP), WNT, fibroblast growth factor (FGF), and transforming growth factor (TGF)-β signaling pathways. New research shows that Fgf18 signaling in hair follicle stem cells synergizes BMP-mediated refractivity, whereas Tgf-β2 signaling counterbalances it. Loss of Fgf18 signaling markedly accelerates anagen initiation, whereas loss of Tgf-β2 signaling significantly delays it, supporting key roles for these pathways in hair cycle timekeeping. PMID:22499035

  14. Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness.

    Science.gov (United States)

    Delmaghani, Sedigheh; Aghaie, Asadollah; Bouyacoub, Yosra; El Hachmi, Hala; Bonnet, Crystel; Riahi, Zied; Chardenoux, Sebastien; Perfettini, Isabelle; Hardelin, Jean-Pierre; Houmeida, Ahmed; Herbomel, Philippe; Petit, Christine

    2016-06-01

    By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal-recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(∗)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(∗)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of-function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium. PMID:27259055

  15. Monitoring intracellular calcium ion dynamics in hair cell populations with Fluo-4 AM.

    Directory of Open Access Journals (Sweden)

    Kateri J Spinelli

    Full Text Available We optimized Fluo-4 AM loading of chicken cochlea to report hair-bundle Ca(2+ signals in populations of hair cells. The bundle Ca(2+ signal reported the physiological state of the bundle and cell; extruding cells had very high bundle Fluo-4 fluorescence, cells with intact bundles and tip links had intermediate fluorescence, and damaged cells with broken tip links had low fluorescence. Moreover, Fluo-4 fluorescence in the bundle correlated with Ca(2+ entry through transduction channels; mechanically activating transduction channels increased the Fluo-4 signal, while breaking tip links with Ca(2+ chelators or blocking Ca(2+ entry through transduction channels each caused bundle and cell-body Fluo-4 fluorescence to decrease. These results show that when tip links break, bundle and soma Ca(2+ decrease, which could serve to stimulate the hair cell's tip-link regeneration process. Measurement of bundle Ca(2+ with Fluo-4 AM is therefore a simple method for assessing mechanotransduction in hair cells and permits an increased understanding of the interplay of tip links, transduction channels, and Ca(2+ signaling in the hair cell.

  16. Hair Dyes Resorcinol and Lawsone Reduce Production of Melanin in Melanoma Cells by Tyrosinase Activity Inhibition and Decreasing Tyrosinase and Microphthalmia-Associated Transcription Factor (MITF) Expression

    OpenAIRE

    Shu-Mei Lee; Yi-Shyan Chen; Chih-Chien Lin; Kuan-Hung Chen

    2015-01-01

    Hair coloring products are one of the most important cosmetics for modern people; there are three major types of hair dyes, including the temporary, semi-permanent and permanent hair dyes. The selected hair dyes (such as ammonium persulfate, sodium persulfate, resorcinol and lawsone) are the important components for hair coloring products. Therefore, we analyzed the effects of these compounds on melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes resorcinol and lawsone ...

  17. How do the medial olivocochlear efferents influence the biomechanics of the outer hair cells and thereby the cochlear amplifier? Simulation results

    Science.gov (United States)

    Saremi, Amin; Stenfelt, Stefan; Verhulst, Sarah

    2015-12-01

    The bottom-up signal pathway, which starts from the outer ear and leads to the brain cortices, gives the classic image of the human sound perception. However, there have been growing evidences in the last six decades for existence of a functional descending network whereby the central auditory system can modulate the early auditory processing, in a top-down manner. The medial olivocochlear efferent fibers project from the superior olivary complex at the brainstem into the inner ear. They are linked to the basal poles of the hair cells by forming synaptic cisterns. This descending network can activate nicotinic cholinergic receptors (nAChR) that increase the membrane conductance of the outer hair cells and thereby modify the magnitude of the active force generated inside the cochlea. The aim of the presented work is to quantitatively investigate how the changes in the biomechanics of the outer hair cells, caused by the efferent activation, manipulate the cochlear responses. This is done by means of a frequency-domain biophysical model of the cochlea [12] where the parameters of the model convey physiological interpretations of the human cochlear structures. The simulations manifest that a doubling of the outer hair cell conductance, due to efferent activation, leads to a frequency-dependent gain reduction along the cochlear duct with its highest effect at frequencies between 1 kHz and 3.5 kHz and a maximum of approximately 10 dB gain reduction at 2 kHz. This amount of the gain inhibition and its frequency dependence reasonably agrees with the experimental data recorded from guinea pig, cat and human cochleae where the medial olivococlear efferents had been elicited by broad-band stimuli. The simulations also indicate that the efferent-induced increase of the outer hair cell conductance increases the best frequency of the cochlear responses, in the basal region. The presented simulations quantitatively confirm that activation of the medial olivocochlear efferents can

  18. T-cell reconstitution after thymus xenotransplantation induces hair depigmentation and loss.

    Science.gov (United States)

    Furmanski, Anna L; O'Shaughnessy, Ryan F L; Saldana, Jose Ignacio; Blundell, Michael P; Thrasher, Adrian J; Sebire, Neil J; Davies, E Graham; Crompton, Tessa

    2013-05-01

    Here we present a mouse model for T-cell targeting of hair follicles, linking the pathogenesis of alopecia to that of depigmentation disorders. Clinically, thymus transplantation has been successfully used to treat T-cell immunodeficiency in congenital athymia, but is associated with autoimmunity. We established a mouse model of thymus transplantation by subcutaneously implanting human thymus tissue into athymic C57BL/6 nude mice. These xenografts supported mouse T-cell development. Surprisingly, we did not detect multiorgan autoimmune disease. However, in all transplanted mice, we noted a striking depigmentation and loss of hair follicles. Transfer of T cells from transplanted nudes to syngeneic black-coated RAG(-/-) recipients caused progressive, persistent coat-hair whitening, which preceded patchy hair loss in depigmented areas. Further transfer experiments revealed that these phenomena could be induced by CD4+ T cells alone. Immunofluorescent analysis suggested that Trp2+ melanocyte-lineage cells were decreased in depigmented hair follicles, and pathogenic T cells upregulated activation markers when exposed to C57BL/6 melanocytes in vitro, suggesting that these T cells are not tolerant to self-melanocyte antigens. Our data raise interesting questions about the mechanisms underlying tissue-specific tolerance to skin antigens. PMID:23303453

  19. Activation of PI3K signaling prevents aminoglycoside-induced hair cell death in the murine cochlea

    Directory of Open Access Journals (Sweden)

    Azadeh Jadali

    2016-06-01

    Full Text Available Loss of sensory hair cells of the inner ear due to aminoglycoside exposure is a major cause of hearing loss. Using an immortalized multipotent otic progenitor (iMOP cell line, specific signaling pathways that promote otic cell survival were identified. Of the signaling pathways identified, the PI3K pathway emerged as a strong candidate for promoting hair cell survival. In aging animals, components for active PI3K signaling are present but decrease in hair cells. In this study, we determined whether activated PI3K signaling in hair cells promotes survival. To activate PI3K signaling in hair cells, we used a small molecule inhibitor of PTEN or genetically ablated PTEN using a conditional knockout animal. Hair cell survival was challenged by addition of gentamicin to cochlear cultures. Hair cells with activated PI3K signaling were more resistant to aminoglycoside-induced hair cell death. These results indicate that increased PI3K signaling in hair cells promote survival and the PI3K signaling pathway is a target for preventing aminoglycoside-induced hearing loss.

  20. From hair to cornea: towards the therapeutic use of hair follicle-derived stem cells in the treatment of limbal stem cell deficiency

    OpenAIRE

    Meyer-Blazejewska, Ewa Anna; Call, Mindy K; Yamanaka, Osamu; Liu, Hongshan; Schlötzer-Schrehardt, Ursula; Kruse, Friedrich E; Kao, Winston W.

    2011-01-01

    Limbal stem cell deficiency (LSCD) leads to severe ocular surface abnormalities that can result in the loss of vision. The most successful therapy currently being used is transplantation of limbal epithelial cell sheets cultivated from a limbal biopsy obtained from the patient´s healthy, contralateral eye or cadaveric tissue. In this study, we investigated the therapeutic potential of murine vibrissae hair follicle bulge-derived stem cells (HFSC) as an autologous SC source for ocular surface ...

  1. Extracted Hair Follicle Outer Root Sheath Cell Suspension for Pigment Cell Restoration in Vitiligo

    OpenAIRE

    Anil Kumar; Sujata Mohanty; Kanika Sahni; Rajesh. Kumar; Somesh Gupta

    2013-01-01

    Vitiligo surgery has come up a long way from punch skin grafts to epidermal cell suspension and latest to the extracted hair follicle outer root sheath cell suspension (EHF-ORS-CS) transplantation. The progressive development from one technique to the other is always in a quest for the best. In the latest development- EHF-ORS-CS, which is an enriched source of follicular inactive melanocyte (melanocyte stem cells), seems to be a good addition to the prevailing cell-based therapies for vitilig...

  2. Expression of mesenchymal stem cell marker CD90 on dermal sheath cells of the anagen hair follicle in canine species

    Directory of Open Access Journals (Sweden)

    F. Mercati

    2009-09-01

    Full Text Available The dermal sheath (DS of the hair follicle is comprised by fibroblast-like cells and extends along the follicular epithelium, from the bulb up to the infundibulum. From this structure, cells with stem characteristics were isolated: they have a mesenchymal origin and express CD90 protein, a typical marker of mesenchymal stem cells. It is not yet really clear in which region of hair follicle these cells are located but some experimental evidence suggests that dermal stem cells are localized prevalently in the lower part of the anagen hair follicle. As there are no data available regarding DS stem cells in dog species, we carried out a morphological analysis of the hair follicle DS and performed both an immunohistochemical and an immunocytochemical investigation to identify CD90+ cells. We immunohistochemically evidenced a clear and abundant positivity to CD90 protein in the DS cells located in the lower part of anagen hair follicle. The positive cells showed a typical fibroblast-like morphology. They were flat and elongated and inserted among bundles of collagen fibres. The whole structure formed a close and continuous sleeve around the anagen hair follicle. Our immunocytochemical study allowed us to localize CD90 protein at the cytoplasmic membrane level.

  3. Screen of FDA-approved drug library reveals compounds that protect hair cells from aminoglycosides and cisplatin

    OpenAIRE

    Vlasits, Anna L.; Simon, Julian A.; Raible, David W.; Rubel, Edwin W; Owens, Kelly N.

    2012-01-01

    Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include aminoglycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic insults is experimentally difficult because of the inaccessibility of the inner ear. We used the ...

  4. Large basolateral processes on type II hair cells comprise a novel processing unit in mammalian vestibular organs

    OpenAIRE

    Pujol, Rémy; Pickett, Sarah B.; Nguyen, Tot Bui; Stone, Jennifer S.

    2014-01-01

    Sensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here, we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes t...

  5. The dermal papilla: an instructive niche for epithelial stem and progenitor cells in development and regeneration of the hair follicle.

    Science.gov (United States)

    Morgan, Bruce A

    2014-07-01

    The dermal papilla (DP) of the hair follicle is both a chemical and physical niche for epithelial progenitor cells that regenerate the cycling portion of the hair follicle and generate the hair shaft. Here, we review experiments that revealed the importance of the DP in regulating the characteristics of the hair shaft and frequency of hair follicle regeneration. More recent work showed that the size of this niche is dynamic and actively regulated and reduction in DP cell number per follicle is sufficient to cause hair thinning and loss. The formation of the DP during follicle neogenesis provides a context to contemplate the mechanisms that maintain DP size and the potential to exploit these processes for hair preservation or restoration. PMID:24985131

  6. Cyclic dermal BMP signaling regulates stem cell activation during hair regeneration

    OpenAIRE

    Plikus, Maksim V; Mayer, Julie; de la Cruz, Damon; Baker, Ruth E.; Maini, Philip K.; Maxson, Robert; Chuong, Cheng-ming

    2008-01-01

    In the age of stem cell engineering, it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life,1 and are an important model for organ regeneration. Hair stem cells located in the follicle bulge2 are regulated by the surrounding micro-environment, or niche3. The activation of such stem cells is cyclic, involving periodic β-catenin activity4–7. In adult mouse, regeneration occurs in waves in...

  7. HCN channels are not required for mechanotransduction in sensory hair cells of the mouse inner ear.

    Directory of Open Access Journals (Sweden)

    Geoffrey C Horwitz

    Full Text Available The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were originally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50-70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear.

  8. Detection without deflection? A hypothesis for direct sensing of sound pressure by hair cells

    Indian Academy of Sciences (India)

    Andrew Bell

    2007-03-01

    It is widely thought that organisms detect sound by sensing the deflection of hair-like projections, the stereocilia, at the apex of hair cells. In the case of mammals, the standard interpretation is that hair cells in the cochlea respond to deflection of stereocilia induced by motion generated by a hydrodynamic travelling wave. But in the light of persistent anomalies, an alternative hypothesis seems to have some merit: that sensing cells (in particular the outer hair cells) may, at least at low intensities, be reacting to a different stimulus – the rapid pressure wave that sweeps through the cochlear fluids at the speed of sound in water. This would explain why fast responses are sometimes seen before the peak of the travelling wave. Yet how could cells directly sense fluid pressure? Here, a model is constructed of the outer hair cell as a pressure vessel able to sense pressure variations across its cuticular pore, and this ‘fontanelle’ model, based on the sensing action of the basal body at this compliant spot, could explain the observed anomalies. Moreover, the fontanelle model can be applied to a wide range of other organisms, suggesting that direct pressure detection is a general mode of sensing complementary to stereociliar displacement.

  9. Identification of soybean proteins from a single cell type: The root hair

    Energy Technology Data Exchange (ETDEWEB)

    Brechenmacher, Laurent; Nguyen, Tran H.; Hixson, Kim K.; Libault, Marc; Aldrich, Joshua T.; Pasa-Tolic, Ljiljana; Stacey, Gary

    2012-11-01

    Root hairs are a terminally differentiated single cell type, mainly involved in water and nutrient uptake from the soil. The soybean root hair cell represents an excellent model for the study of single cell systems biology. In this study, we identified 5702 proteins, with at least two peptides, from soybean root hairs using an accurate mass and time tag approach, establishing the most comprehensive proteome reference map of this single cell type. We also showed that trypsin is the most appropriate enzyme for soybean proteomic studies by performing an in silico digestion of the soybean proteome database using different proteases. Although the majority of proteins identified in this study are involved in basal metabolism, the function of others are more related to root hair formation/function and include proteins involved in nutrient uptake (transporters) or vesicular trafficking (cytoskeleton and RAB proteins). Interestingly, some of these proteins appear to be specifically expressed in root hairs and constitute very good candidates for further studies to elucidate unique features of this single cell model.

  10. Increased symplasmic permeability in barley root epidermal cells correlates with defects in root hair development

    OpenAIRE

    Marzec, M; Muszynska, A. (Agata); Melzer, M.; Sas-Nowosielska, H; Kurczynska, E U; Wick, S.

    2013-01-01

    It is well known that the process of plant cell differentiation depends on the symplasmic isolation of cells. Before starting the differentiation programme, the individual cell or group of cells should restrict symplasmic communication with neighbouring cells. We tested the symplasmic communication between epidermal cells in the different root zones of parental barley plants Hordeum vulgare L., cv. ‘Karat’ with normal root hair development, and two root hairless mutants (rhl1.a and rhl1.b). T...

  11. Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth

    Science.gov (United States)

    Zhou, Linli; Xu, Mingang; Yang, Yongguang; Yang, Kun; Wickett, Randall R.; Andl, Thomas; Millar, Sarah E.

    2016-01-01

    The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth. PMID:27472062

  12. Using Cortical Auditory Evoked Potentials as a predictor of speech perception ability in Auditory Neuropathy Spectrum Disorder and conditions with ANSD-like clinical presentation

    OpenAIRE

    Stirling, Francesca

    2015-01-01

    Auditory Neuropathy Spectrum Disorder (ANSD) is diagnosed by the presence of outer hair cell function, and absence or severe abnormality of the auditory brainstem response (ABR). Within the spectrum of ANSD, level of severity varies greatly in two domains: hearing thresholds can range from normal levels to a profound hearing loss, and degree of speech perception impairment also varies. The latter gives a meaningful indication of severity in ANSD. As the ABR does not relate to functional perfo...

  13. Insulin-like growth factor 1: A novel treatment for the protection or regeneration of cochlear hair cells.

    Science.gov (United States)

    Yamahara, Kohei; Yamamoto, Norio; Nakagawa, Takayuki; Ito, Juichi

    2015-12-01

    Sensorineural hearing loss (SNHL) is mainly caused by cochlear hair cell damage. Because cochlear hair cells and supporting cells lose their ability to proliferate in postnatal mammals, SNHL was thought to be an intractable disease. The maintenance of hair cell and supporting cell numbers after cochlear injury is therefore important for the treatment of sensorineural hearing loss. To achieve such treatment, protection and/or regeneration of hair cells is necessary. Progress in cochlear injury research, developmental biology, and regenerative medicine has led to the discovery of cochlear hair cells being protected or regenerated not only by direct reaction of hair cells themselves but also by that of supporting cells. Insulin-like growth factor 1 (IGF1) is considered a novel and potent treatment for SNHL based on the findings of various in vivo and in vitro experiments and clinical trials. The application of IGF1 maintains hair cell number of postnatal mammalian cochleae after various kinds of ototoxicity including aminoglycoside treatment, noise exposure, and ischemia. The positive effects of IGF1 on hair cell damage have been confirmed with in vivo animal experiments; hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic glucocorticoid treatment has also been shown to occur following IGF1 treatment. The mechanisms of IGF1-induced maintenance of hair cell number have been investigated using a cochlear explant culture system, which demonstrated that IGF1 acts on supporting cells, leading to the inhibition of hair cell apoptosis and the proliferation of supporting cells. Netrin1 has furthermore been identified as one of the effectors whose expression is increased by IGF1 treatment. PMID:25937136

  14. Bio-inspired piezoelectric artificial hair cell sensor fabricated by powder injection molding

    Science.gov (United States)

    Han, Jun Sae; Oh, Keun Ha; Moon, Won Kyu; Kim, Kyungseop; Joh, Cheeyoung; Seo, Hee Seon; Bollina, Ravi; Park, Seong Jin

    2015-12-01

    A piezoelectric artificial hair cell sensor was fabricated by the powder injection molding process in order to make an acoustic vector hydrophone. The entire process of powder injection molding was developed and optimized for PMN-PZT ceramic powder. The artificial hair cell sensor, which consists of high aspect ratio hair cell and three rectangular mechanoreceptors, was precisely fabricated through the developed powder injection molding process. The density and the dielectric property of the fabricated sensor shows 98% of the theoretical density and 85% of reference dielectric property of PMN-PZT ceramic powder. With regard to homogeneity, three rectangular mechanoreceptors have the same dimensions, with 3 μm of tolerance with 8% of deviation of dielectric property. Packaged vector hydrophones measure the underwater acoustic signals from 500 to 800 Hz with -212 dB of sensitivity. Directivity of vector hydrophone was acquired at 600 Hz as analyzing phase differences of electric signals.

  15. Type I hair cell degeneration in the utricular macula of the waltzing guinea pig

    DEFF Research Database (Denmark)

    Severinsen, Stig A; Raarup, Merete Krog; Ulfendahl, Mats;

    2008-01-01

    Waltzing guinea pigs are an inbred guinea pig strain with a congenital and progressive balance and hearing disorder. A unique rod-shaped structure is found in the type I vestibular hair cells, that traverses the cell in an axial direction, extending towards the basement membrane. The present study...

  16. PARP-1-modulated AIF translocation is involved in streptomycin-induced cochlear hair cell death.

    Science.gov (United States)

    Song, Yongdong; Fan, Zhaomin; Bai, Xiaohui; Liu, Wenwen; Han, Yuechen; Xu, Lei; Wang, Mingming; Li, Jianfeng; Zheng, Qingyin; Zhang, Daogong; Wang, Haibo

    2016-06-01

    Conclusion SM-induced dose- and location-dependent cochlear hair cell death in vitro. AIF might be translocated from mitochondria to nucleus and cytoplasm within SM-treated hair cells. The translocation of AIF might be modulated by PARP-1. Objective Streptomycin (SM), one of the widely used aminoglycoside nowadays, is still causing significant permanent sensorineural hearing loss owing to sensory hair cell death. This study was designed to investigate the role of apoptosis-inducing factor (AIF), an important mitochondrial cell death regulator, in SM ototoxicity within neonatal rat cochleae and HEI-OC1 cells. Methods The viability of HEI-OC1 cells was quantified by MTT assay. AIF, PARP-1, and myosin VIIa distributions were achieved by immunofluorescence. mRNA and protein expression of AIF and PARP-1 were examined by q-PCR and Western-blot. Results The hair cell loss was concomitant with the SM concentration variation, and aggravated from apical to basal turn. AIF was detected in nuclear region and AIF mRNA was up-regulated after SM incubation. Besides, AIF protein expression in mitochondria was decreased, whereas in cytosol it was increased. PARP-1 mRNA and protein were also up-regulated. 3-AB could attenuate the cell death and reverse the changes of AIF distribution by blocking PARP-1. PMID:26963167

  17. Dynamic changes in hair cell ribbon synapse induced by loss of spiral ganglion neurons in mice

    Institute of Scientific and Technical Information of China (English)

    Yuan Yasheng; Chi Fanglu

    2014-01-01

    Background Previous studies have suggested that primary degeneration of hair cells causes secondary degeneration of spiral ganglion neurons (SGNs),but the effect of SGN degeneration on hair cells has not been studied.In the adult mouse inner ear ouabain can selectively and permanently induce the degeneration of type 1 SGNs while leaving type 2 SGNs,efferent fibers,and sensory hair cells relatively intact.This study aimed to investigate the dynamic changes in hair cell ribbon synapse induced by loss of SGNs using ouabain application to the round window niche of adult mice.Methods In the analysis,24 CBA/CAJ mice aged 8-10 weeks,were used,of which 6 normal mice were used as the control group.After ouabain application in the round window niche 6 times in an hour,ABR threshold shifts at least 30 dB in the three experimental groups which had six mice for 1-week group,six for 1-month group,and six for 3-month group.All 24 animals underwent function test at 1 week and then immunostaining at 1 week,1 month,and 3 months.Results The loss of neurons was followed by degeneration of postsynaptic specializations at the afferent synapse with hair cells.One week after ouabain treatment,the nerve endings of type 1 SGNs and postsynaptic densities,as measured by Na/K ATPase and PSD-95,were affected but not entirely missing,but their partial loss had consequences for synaptic ribbons that form the presynaptic specialization at the synapse between hair cells and primary afferent neurons.Ribbon numbers in inner hair cells decreased (some of them broken and the ribbon number much decreased),and the arrangement of the synaptic ribbons had undergone a dynamic reorganization:ribbons with or without associated postsynaptic densities moved from their normal location in the basal membrane of the cell to a more apical location and the neural endings alone were also found at more apical locations without associated ribbons.After 1 month,when the neural postsynaptic densities had completed their

  18. Tension Sensitivity of Prestin: Comparison with the Membrane Motor in Outer Hair Cells

    OpenAIRE

    Dong, X.-X.; Iwasa, K H

    2004-01-01

    The membrane motor in outer hair cells undergoes conformational transitions involving charge displacement of ∼0.8 e across the membrane and changes of ∼4 nm2 in its membrane area. Previous reports have established that the charge transfer in the membrane motor and that in prestin, a membrane protein in the plasma membrane of outer hair cells, are approximately equal. Here, we determine the membrane area changes based on its sensitivity to membrane tension. We found that prestin does undergo a...

  19. Increased symplasmic permeability in barley root epidermal cells correlates with defects in root hair development.

    Science.gov (United States)

    Marzec, M; Muszynska, A; Melzer, M; Sas-Nowosielska, H; Kurczynska, E U

    2014-03-01

    It is well known that the process of plant cell differentiation depends on the symplasmic isolation of cells. Before starting the differentiation programme, the individual cell or group of cells should restrict symplasmic communication with neighbouring cells. We tested the symplasmic communication between epidermal cells in the different root zones of parental barley plants Hordeum vulgare L., cv. 'Karat' with normal root hair development, and two root hairless mutants (rhl1.a and rhl1.b). The results clearly show that symplasmic communication was limited during root hair differentiation in the parental variety, whereas in both root hairless mutants epidermal cells were still symplasmically connected in the corresponding root zone. This paper is the first report on the role of symplasmic isolation in barley root cell differentiation, and additionally shows that a disturbance in the restriction of symplasmic communication is present in root hairless mutants. PMID:23927737

  20. In vivo Notch Reactivation in Differentiating Cochlear Hair Cells Induces Sox2 and Prox1 Expression but Does Not Disrupt Hair Cell Maturation

    OpenAIRE

    Liu, Zhiyong; Owen, Thomas; Fang, Jie; Srinivasan, R. Sathish; Zuo, Jian

    2012-01-01

    Notch signaling is active in mouse cochlear prosensory progenitors but declines in differentiating sensory hair cells (HCs). Overactivation of the Notch1 intracellular domain (NICD) in progenitors blocks HC fate commitment and/or differentiation. However, it is not known whether reactivation of NICD in differentiating HCs also interrupts their developmental program and reactivates its downstream targets. By analyzing Atoh1CreER+; Rosa26-NICDloxp/+ or Atoh1CreER+; Rosa26-NICDloxp/+; RBP-Jloxp/...

  1. Direct mechanical stimulation of tip links in hair cells through DNA tethers

    Science.gov (United States)

    Basu, Aakash; Lagier, Samuel; Vologodskaia, Maria; Fabella, Brian A; Hudspeth, AJ

    2016-01-01

    Mechanoelectrical transduction by hair cells commences with hair-bundle deflection, which is postulated to tense filamentous tip links connected to transduction channels. Because direct mechanical stimulation of tip links has not been experimentally possible, this hypothesis has not been tested. We have engineered DNA tethers that link superparamagnetic beads to tip links and exert mechanical forces on the links when exposed to a magnetic-field gradient. By pulling directly on tip links of the bullfrog's sacculus we have evoked transduction currents from hair cells, confirming the hypothesis that tension in the tip links opens transduction channels. This demonstration of direct mechanical access to tip links additionally lays a foundation for experiments probing the mechanics of individual channels. DOI: http://dx.doi.org/10.7554/eLife.16041.001 PMID:27331611

  2. The Olivocochlear Reflex Strength and Cochlear Sensitivity are Independently Modulated by Auditory Cortex Microstimulation

    OpenAIRE

    Dragicevic, Constantino D.; Aedo, Cristian; León, Alex; Bowen, Macarena; Jara, Natalia; Terreros, Gonzalo; Robles, Luis; Delano, Paul H.

    2015-01-01

    In mammals, efferent projections to the cochlear receptor are constituted by olivocochlear (OC) fibers that originate in the superior olivary complex. Medial and lateral OC neurons make synapses with outer hair cells and with auditory nerve fibers, respectively. In addition to the OC system, there are also descending projections from the auditory cortex that are directed towards the thalamus, inferior colliculus, cochlear nucleus, and superior olivary complex. Olivocochlear function can be as...

  3. Connecting the ear to the brain: molecular mechanisms of auditory circuit assembly

    OpenAIRE

    Appler, Jessica M; Goodrich, Lisa V.

    2011-01-01

    Our sense of hearing depends on precisely organized circuits that allow us to sense, perceive, and respond to complex sounds in our environment, from music and language to simple warning signals. Auditory processing begins in the cochlea of the inner ear, where sounds are detected by sensory hair cells and then transmitted to the central nervous system by spiral ganglion neurons, which faithfully preserve the frequency, intensity, and timing of each stimulus. During the assembly of auditory c...

  4. The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea

    Directory of Open Access Journals (Sweden)

    Anna Kirjavainen

    2015-03-01

    Full Text Available Hair cells of the organ of Corti (OC of the cochlea exhibit distinct planar polarity, both at the tissue and cellular level. Planar polarity at tissue level is manifested as uniform orientation of the hair cell stereociliary bundles. Hair cell intrinsic polarity is defined as structural hair bundle asymmetry; positioning of the kinocilium/basal body complex at the vertex of the V-shaped bundle. Consistent with strong apical polarity, the hair cell apex displays prominent actin and microtubule cytoskeletons. The Rho GTPase Cdc42 regulates cytoskeletal dynamics and polarization of various cell types, and, thus, serves as a candidate regulator of hair cell polarity. We have here induced Cdc42 inactivation in the late-embryonic OC. We show the role of Cdc42 in the establishment of planar polarity of hair cells and in cellular patterning. Abnormal planar polarity was displayed as disturbances in hair bundle orientation and morphology and in kinocilium/basal body positioning. These defects were accompanied by a disorganized cell-surface microtubule network. Atypical protein kinase C (aPKC, a putative Cdc42 effector, colocalized with Cdc42 at the hair cell apex, and aPKC expression was altered upon Cdc42 depletion. Our data suggest that Cdc42 together with aPKC is part of the machinery establishing hair cell planar polarity and that Cdc42 acts on polarity through the cell-surface microtubule network. The data also suggest that defects in apical polarization are influenced by disturbed cellular patterning in the OC. In addition, our data demonstrates that Cdc42 is required for stereociliogenesis in the immature cochlea.

  5. DAPT mediates atoh1 expression to induce hair cell-like cells

    Science.gov (United States)

    Ren, Hongmiao; Guo, Weiwei; Liu, Wei; Gao, Weiqiang; Xie, Dinghua; Yin, Tuanfang; Yang, Shiming; Ren, Jihao

    2016-01-01

    Hearing loss is currently an incurable degenerative disease characterized by a paucity of hair cells (HCs), which cannot be spontaneously replaced in mammals. Recent technological advancements in gene therapy and local drug delivery have shed new light for hearing loss. Atoh1, also known as Math1, Hath1, and Cath1, is a proneural basic helix-loop-helix (bHLH) transcription factor that is essential for HC differentiation. At various stages in development, Atoh1 activity is sufficient to drive HC differentiation in the cochlea. Thus, Atoh1 related gene therapy is the most promising option for HC induction. DAPT, an inhibitor of Notch signaling, enhances the expression of Atoh1 indirectly, which in turn promotes the induction of a HC fate. Here, we show that DAPT cooperates with Atoh1 to synergistically promote HC fate in ependymal cells in vitro and promote hair cell regeneration in the cultured basilar membrane (BM) which mimics the microenvironment in vivo. Taken together, our findings demonstrated that DAPT is sufficient to induce HC-like cells via enhancing of the expression of Atoh1 to inhibit the progression of HC apoptosis and to induce new HC formation.

  6. Micronucleus frequency in exfoliated buccal cells from hairdresser who expose to hair products

    Directory of Open Access Journals (Sweden)

    Koh Hui Yee

    2015-06-01

    Full Text Available Background: Hairdresser is one of the fastest growing occupations in today’s society. Hairdresser help styling, cutting, colouring, perming, curling, straightening hair and various treatment to customer. Somehow, hairdresser are constantly exposed to chemical substances such as aromatic amines, hydrogen peroxide, thioglycolic acid, formaldehyde in hair products which can cause damage to human’s genome. Micronucleus is one of the effective biomarker for processes associated with the induction of DNA damage. Purpose: The aim of this study was to determine the micronucleus frequencies in buccal mucosa epithelial cells of hairdresser who were exposed to chemical of hair products. Method: This study was conducted on twenty female subjects, who were divided into 2 groups: exposed and non-exposed (control group. All subjects recruited were working in the same beauty salon. Buccal cells were obtained from each individual by using cytobrush. The cells were stained with modified Feulgen-Ronssenback method and counting of micronucleus per 1000 cell was done under light microscope. The data were analyzed using independent t-test and one-way Anova (p<0.05. Result: The result showed a significant difference in micronucleus frequency between 2 groups. There were a significantly increase of micronucleus frequency in hairdressers and increase of  micronucleus frequency with the longer duration of exposure. Conclusion: It concluded that the chemical substances of hair products had affected the micronucleus frequency ofthe epithelial cells in buccal mucosa of hairdressers.

  7. Phosphatidylserine-positive particles in the apical domain of sensory hair cells

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-rui; Alfred Nuttall

    2006-01-01

    Apical membrane recycling has been proposed to be important for normal hair cell function. The current study reports an in vitro work that demonstrates the presence of phosphatidylserine (PS) and PS-positive vesicles labeled by Annexin V in the apical portion of hair cells. The following characteristics of the PS-positive vesicles were noticed using scanning confocal fluorescence microscopy: (1) variable sizes around 200 nm; (2)variable distribution patterns (either uniformly along individual stereocilia in the hair bundle or irregular) in the stereocilia from cell to cell; (3) variable sizes and numbers at locations along the border of the cuticular plate (CP),with a large number of them located at the vestigal kinocilial location; (4) motility with some of the vesicles during the observation period; (5) increase in PS labeling and the number of PS-positive vesicles after loud sound stimulation; and (6) decreased PS labeling and PS-positive vesicle numbers following treatment with LY-294002, a PI3 -kinase inhibitor. These results suggest that the presence of PS-positive vesicles at the apical area of hair cells may be indicative of vesicle shedding or transportation of a protein or rafts.

  8. Daunomycin accumulation and induction of programmed cell death in rat hair follicles

    DEFF Research Database (Denmark)

    Shin, Masashi; Larsson, Lars-Inge; Hougaard, David M.;

    2009-01-01

    -positive matrix cells are detectable up to 48 h after injection and exhibit a characteristic granular morphology, which is not observed in saline-injected controls. TUNEL-staining has revealed that DM injection induces programmed cell death (PCD) in rat hair follicles. Cells undergoing PCD are detectable as late......The anthracycline antibiotic daunomycin (DM) is useful for the treatment of leukemia but has side-effects such as alopecia. Using immunocytochemistry, we show that, after a single i.v. injection, DM accumulates in the nuclei of matrix cells and in the outer root sheath of hair follicles. DM...... and in the outer root sheath. Ultrastructural immunocytochemistry has shown the presence of DM-positive cells with two different types of morphology. About half of the immunopositive cells exhibit a morphology typical of classical apoptosis (PCD type 1), whereas the other half show signs of autophagic...

  9. Induction of hair growth by insulin-like growth factor-1 in 1,763 MHz radiofrequency-irradiated hair follicle cells.

    Directory of Open Access Journals (Sweden)

    Sun-Young Yoon

    Full Text Available Radiofrequency (RF radiation does not transfer high energy to break the covalent bonds of macromolecules, but these low energy stimuli might be sufficient to induce molecular responses in a specific manner. We monitored the effect of 1,763 MHz RF radiation on cultured human dermal papilla cells (hDPCs by evaluating changes in the expression of cytokines related to hair growth. The expression of insulin-like growth factor-1 (IGF-1 mRNA in hDPCs was significantly induced upon RF radiation at the specific absorption rate of 10 W/kg, which resulted in increased expression of B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL-2 and cyclin D1 (CCND1 proteins and increased phosphorylation of MAPK1 protein. Exposure to 10 W/kg RF radiation 1 h per day for 7 days significantly enhanced hair shaft elongation in ex vivo hair organ cultures. In RF-exposed follicular matrix keratinocytes in the hair bulb, the expression of Ki-67 was increased, while the signal for terminal deoxynucleotidyl transferase dUTP nick end labeling was reduced. From these results, we suggest that 1,763 MHz RF exposure stimulates hair growth in vitro through the induction of IGF-1 in hDPCs.

  10. Hair cells use active zones with different voltage dependence of Ca2+ influx to decompose sounds into complementary neural codes.

    Science.gov (United States)

    Ohn, Tzu-Lun; Rutherford, Mark A; Jing, Zhizi; Jung, Sangyong; Duque-Afonso, Carlos J; Hoch, Gerhard; Picher, Maria Magdalena; Scharinger, Anja; Strenzke, Nicola; Moser, Tobias

    2016-08-01

    For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca(2+) influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca(2+) influx ranged over ∼20 mV. Ca(2+) influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca(2+) channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca(2+) influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca(2+) influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca(2+) influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca(2+) channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs. PMID:27462107

  11. Modeling auditory perception of individual hearing-impaired listeners

    DEFF Research Database (Denmark)

    Jepsen, Morten Løve; Dau, Torsten

    showed that, in most cases, the reduced or absent cochlear compression, associated with outer hair-cell loss, quantitatively accounts for broadened auditory filters, while a combination of reduced compression and reduced inner hair-cell function accounts for decreased sensitivity and slower recovery from...... selectivity. Three groups of listeners were considered: (a) normal hearing listeners; (b) listeners with a mild-to-moderate sensorineural hearing loss; and (c) listeners with a severe sensorineural hearing loss. A fixed set of model parameters were derived for each hearing-impaired listener. The simulations...

  12. Hair cell tufts and afferent innervation of the bullfrog crista ampullaris

    Science.gov (United States)

    Myers, Steven F.; Lewis, Edwin R.

    1990-01-01

    Within the bullfrog semicircular canal crista, hair cell tuft types were defined and mapped with the aid of scanning electron microscopy. Dye-filled planar afferent axons had mean distal axonal diameters of 1.6-4.9 microns, highly branched arbors, and contacted 11-24 hair cells. Dye-filled isthmus afferent axons had mean distal axonal diameters of 1.8-7.9 microns, with either small or large field arbors contacting 4-9 or 25-31 hair cells. The estimated mean number of contacts per innervated hair cell was 2.2 for planar and 1.3 for isthmus afferent neurons. Data on evoked afferent responses were available only for isthmus units that were observed to respond to our microrotational stimuli. Of 21 such afferent neurons, eight were successfully dye-filled. Within this sample, high-gain units had large field arbors and lower-gain units had small field arbors. The sensitivity of each afferent neuron was analyzed in terms of noise equivalent input (NEI), the stimulus amplitude for which the afferent response amplitude is just equivalent to the rms deviation of the instantaneous spike rate. NEI for isthmus units varied from 0.63 to 8.2 deg/s; the mean was 3.2 deg/s.

  13. XIRP2, an Actin-Binding Protein Essential for Inner Ear Hair-Cell Stereocilia

    Directory of Open Access Journals (Sweden)

    Déborah I. Scheffer

    2015-03-01

    Full Text Available Hair cells of the inner ear are mechanoreceptors for hearing and balance, and proteins highly enriched in hair cells may have specific roles in the development and maintenance of the mechanotransduction apparatus. We identified XIRP2/mXinβ as an enriched protein likely to be essential for hair cells. We found that different isoforms of this protein are expressed and differentially located: short splice forms (also called XEPLIN are targeted more to stereocilia, whereas two long isoforms containing a XIN-repeat domain are in both stereocilia and cuticular plates. Mice lacking the Xirp2 gene developed normal stereocilia bundles, but these degenerated with time: stereocilia were lost and long membranous protrusions emanated from the nearby apical surfaces. At an ultrastructural level, the paracrystalline actin filaments became disorganized. XIRP2 is apparently involved in the maintenance of actin structures in stereocilia and cuticular plates of hair cells, and perhaps in other organs where it is expressed.

  14. T-Cell Reconstitution after Thymus Xenotransplantation Induces Hair Depigmentation and Loss

    OpenAIRE

    Furmanski, A. L.; O Shaughnessy, R. F.; Saldana, J. I.; Blundell, M. P.; Thrasher, A. J.; Sebire, N J; Davies, E G; Crompton, T.

    2013-01-01

    Here we present a mouse model for T-cell targeting of hair follicles, linking the pathogenesis of alopecia to that of depigmentation disorders. Clinically, thymus transplantation has been successfully used to treat T-cell immunodeficiency in congenital athymia, but is associated with autoimmunity. We established a mouse model of thymus transplantation by subcutaneously implanting human thymus tissue into athymic C57BL/6 nude mice. These xenografts supported mouse T-cell development. Surprisin...

  15. Trace element distribution in the hair of some sickle cell anemia patients and controls

    International Nuclear Information System (INIS)

    Hair samples of some young sickle cell anemia (SCA) and Control patients in Nigeria were analyzed for 12 elements, viz, Se, Hg, Cr, Fe, Zn, Co, Cu, Br, As, Sb, Na, and Sc, using instrumental Neutron Activation Analysis (INAA). With the exception of Cu, which was found to be significantly higher in the hair of SCA patients (at the 0.05 level of the t-test), there were generally no significant differences in elemental concentrations within the two groups. A preliminary study of the elemental contents of the fingernails of the same subjects showed a higher abundance of most of the elements in nail than in hair. These preliminary results were compared with similar studies form some other parts of the world

  16. Three-dimensional architecture of hair-cell linkages as revealedby electron-microscopic tomography

    Energy Technology Data Exchange (ETDEWEB)

    Auer, Manfred; Koster, Bram; Ziese, Ulrike; Bajaj, Chandrajit; Volkmann, Niels; Wang, Da Neng; Hudspeth, A. James

    2006-07-28

    The senses of hearing and balance rest upon mechanoelectrical transduction by the hair bundles of hair cells in the inner ear. Located at the apical cellular surface, each hair bundle comprises several tens of stereocilia and a single kinocilium that are interconnected by extracellular proteinaceous links. Using electron-microscopic tomography of bullfrog saccular sensory epithelia, we examined the three-dimensional structures of ankle or basal links, kinociliary links, and tip links. We observed clear differences in the dimensions and appearances of the three links. We found two distinct populations of tip links suggestive of the involvement of two proteins or splice variants. We noted auxiliary links connecting the upper portions of tip links to the taller stereocilia. Tip links and auxiliary links show a tendency to adopt a globular conformation when disconnected from the membrane surface.

  17. LINKING DEAFNESS GENES TO HAIR-BUNDLE DEVELOPMENT AND FUNCTION

    OpenAIRE

    Petit, Christine; Richardson, Guy P.

    2009-01-01

    The identification of genes underlying monogenic, early-onset forms of deafness in humans has provided unprecedented insight into the molecular mechanisms of hearing in the peripheral auditory system. The molecules involved in the development and function of the cochlea eluded characterization until recently due to the paucity of the principle cell types present in cochlear hair cells, yet a genetic approach has circumvented this problem and succeeded in identifying proteins and deciphering s...

  18. Sensory transduction at the frog semicircular canal: how hair cell membrane potential controls junctional transmission.

    Directory of Open Access Journals (Sweden)

    Riccardo Fesce

    2015-06-01

    Full Text Available At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs, due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot be studied at the intact semicircular canal. To circumvent the problem, we combined patch-clamp recordings at the isolated hair cell and electrophysiological recordings at the cytoneural junction in the intact preparation. At isolated hair cells, the K channel blocker TEA is shown to block a fraction of total voltage-dependent K-conductance (IKD that depends on TEA concentration but not on membrane potential (Vm. Considering the bioelectric properties of the hair cell, as previously characterized by this lab, a fixed fractional block of IKD is shown to induce a relatively fixed shift in Vm, provided it lies in the range -30 to -10 mV. The same concentrations of TEA were applied to the intact labyrinth while recording from single afferent fibers of the posterior canal, at rest and during mechanical stimulation. At the peak of stimulation, TEA produced increases in mEPSP rate that were linearly related to the shifts produced by the same TEA concentrations (0.1-3 mM in hair cell Vm (0.7-5 mV, with a slope of 29.8 Hz/mV. The membrane potential of the hair cell is not linearly related to receptor conductance, so that the slope of quantal release vs. receptor conductance depends on the prevailing Vm (19.8 Hz/nS at -20 mV; 11 Hz/nS at -10 mV. Changes in mEPSP peak size were negligible at rest as well as during stimulation. Since ample spatial summation of mEPSPs occurs at the afferent terminal and threshold-governed spike firing is intrinsically nonlinear, the observed increases in mEPSP frequency, though not very large, may suffice to trigger afferent spike discharge.

  19. Continuous Hair Cell Turnover in the Inner Ear Vestibular Organs of a Mammal, the Daubenton's Bat (Myotis daubentonii)

    Science.gov (United States)

    Kirkegaard, M.; Jørgensen, J. M.

    In both humans and mice the number of hair cells in the inner ear sensory epithelia declines with age, indicating cell death (Park et al. 1987; Rosenhall 1973). However, recent reports demonstrate the ability of the vestibular sensory epithelia to regenerate after injury (Forge et al. 1993, 1998; Kuntz and Oesterle 1998; Li and Forge 1997; Rubel et al. 1995; Tanyeri et al. 1995). Still, a continuous hair cell turnover in the vestibular epithelia has not previously been demonstrated in mature mammals. Bats are the only flying mammals, and they are known to live to a higher age than animals of equal size. The maximum age of many species is 20years, with average lifespans of 4-6years (Schober and Grimmberger 1989). Further, the young are fully developed and able to fly at the age of 2months, and thus the vestibular organs are thought to be differentiated at that age. Consequently, long-lived mammals such as bats might compensate for the loss of hair cells by producing new hair cells in their postembryonic life. Here we show that the utricular macula of adult Daubenton's bats (more than 6months old) contains innervated immature hair cells as well as apoptotic hair cells, which strongly indicates a continuous turnover of hair cells, as previously demonstrated in birds.

  20. Membrane tether formation from voltage-clamped outer hair cells using optical tweezers

    Science.gov (United States)

    Qian, Feng; Ermilov, Sergey A.; Murdock, David R.; Brownell, William E.; Anvari, Bahman

    2004-06-01

    Outer hair cells contribute an active mechanical feedback to the vibrations of the cochlear structures resulting in the high sensitivity and frequency selectivity of normal hearing. We have designed and implemented a novel experimental setup that combines optical tweezers with patch-clamp apparatus to investigate the electromechanical properties of cellular plasma membranes. A micron-size bead trapped by the optical tweezers is brought in contact with the membrane of a voltage-clamped cell, and subsequently moved away to form a plasma membrane tether. Bead displacement during tether elongation is monitored by a quadrant photodetector to obtain time-resolved measurements of the tethering force. Salient information associated with the mechanical properties of the membrane tether can thus be obtained. Tethers can be pulled from the cell membrane at different holding potentials, and the tether force response can be measured while changing transmembrane potential. Experimental results from outer hair cells and human embryonic kidney cells are presented.

  1. Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool.

    Science.gov (United States)

    Mesa, Kailin R; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Y; Brown, Samara; Gonzalez, David G; Blagoev, Krastan B; Haberman, Ann M; Greco, Valentina

    2015-06-01

    Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbours. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through transforming growth factor (TGF)-β activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool, as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviours and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis. PMID:25849774

  2. Niche induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool

    Science.gov (United States)

    Mesa, Kailin R.; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Yang; Brown, Samara; Gonzalez, David; Blagoev, Krastan B.; Haberman, Ann M.; Greco, Valentina

    2015-01-01

    Summary Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression)1,2. Contrary to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration3. Here we show by intravital microscopy in live mice4–6 that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbors. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through TGFβ activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviors and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis. PMID:25849774

  3. 2,3-Dihydroxybenzoic acid attenuates kanamycin-induced volume reduction in mouse utricular type I hair cells

    DEFF Research Database (Denmark)

    Severinsen, Stig Åvall; Kirkegaard, Mette; Nyengaard, Jens Randel

    2006-01-01

    interest. This study estimates cellular quantitative changes in the utricular macula of mice following systemic treatment with kanamycin alone or in combination with DHB. The animals were injected with either saline, kanamycin or kanamycin+DHB for 15 days and perfusion fixed three weeks after last...... macula, hair cell type I and supporting cells decreased significantly in animals injected with kanamycin but not in animals co-treated with DHB. Hair and supporting cell numbers remained unchanged in all three groups. In conclusion, the kanamycin-induced volume reduction of type I hair cells was...

  4. The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.

    Directory of Open Access Journals (Sweden)

    Jennifer Olt

    Full Text Available Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing.

  5. Multi-layered environmental regulation on the homeostasis of stem cells: The saga of hair growth and alopecia

    OpenAIRE

    Chen, Chih-Chiang; Chuong, Cheng Ming

    2012-01-01

    Stem cells are fascinating because of their potential in regenerative medicine. Stem cell homeostasis has been thought to be mainly regulated by signals from their adjacent micro-environment named the “stem cell niche”. However, recent studies reveal that there can be multiple layers of environmental controls. Here we review these environmental controls using the paradigm of hair stem cells, because to observe and analyze the growth of hair is easier due to their characteristic cyclic regener...

  6. Hair cosmetics and camouflage technics

    OpenAIRE

    Zahide Eriş Eken; Banu Taşkın; Sibel Alper

    2014-01-01

    Hair is composed of a mixture of trace elements in small quantities, proteins, lipids and water. Proteins consist of helical polypeptide amino acid molecules. In the hair cells; polypeptide chains of keratin protein would be organized in filaments. In recent years, hair cosmetics showed a significant change and development. The content of shampoos which is used to cleanse the hair has enhanced significantly. Hair conditioner, hair styling products, pomades, brilliantine, and gloss sprays, hai...

  7. An auditory-periphery model of the effects of acoustic trauma on auditory nerve responses

    Science.gov (United States)

    Bruce, Ian C.; Sachs, Murray B.; Young, Eric D.

    2003-01-01

    Acoustic trauma degrades the auditory nerve's tonotopic representation of acoustic stimuli. Recent physiological studies have quantified the degradation in responses to the vowel eh and have investigated amplification schemes designed to restore a more correct tonotopic representation than is achieved with conventional hearing aids. However, it is difficult from the data to quantify how much different aspects of the cochlear pathology contribute to the impaired responses. Furthermore, extensive experimental testing of potential hearing aids is infeasible. Here, both of these concerns are addressed by developing models of the normal and impaired auditory peripheries that are tested against a wide range of physiological data. The effects of both outer and inner hair cell status on model predictions of the vowel data were investigated. The modeling results indicate that impairment of both outer and inner hair cells contribute to degradation in the tonotopic representation of the formant frequencies in the auditory nerve. Additionally, the model is able to predict the effects of frequency-shaping amplification on auditory nerve responses, indicating the model's potential suitability for more rapid development and testing of hearing aid schemes.

  8. Why Does Hair Turn Gray?

    Science.gov (United States)

    ... sun . The dark or light color of someone's hair depends on how much melanin each hair contains. As we get older, the pigment cells ... cells in a hair follicle, that strand of hair will no longer contain as much melanin and will become a more transparent color — like ...

  9. Transdifferentiation of Human Hair Follicle Mesenchymal Stem Cells into Red Blood Cells by OCT4

    Directory of Open Access Journals (Sweden)

    Zhijing Liu

    2015-01-01

    Full Text Available Shortage of red blood cells (RBCs, erythrocytes can have potentially life-threatening consequences for rare or unusual blood type patients with massive blood loss resulting from various conditions. Erythrocytes have been derived from human pluripotent stem cells (PSCs, but the risk of potential tumorigenicity cannot be ignored, and a majority of these cells produced from PSCs express embryonic ε- and fetal γ-globins with little or no adult β-globin and remain nucleated. Here we report a method to generate erythrocytes from human hair follicle mesenchymal stem cells (hHFMSCs by enforcing OCT4 gene expression and cytokine stimulation. Cells generated from hHFMSCs expressed mainly the adult β-globin chain with minimum level of the fetal γ-globin chain. Furthermore, these cells also underwent multiple maturation events and formed enucleated erythrocytes with a biconcave disc shape. Gene expression analyses showed that OCT4 regulated the expression of genes associated with both pluripotency and erythroid development during hHFMSC transdifferentiation toward erythroid cells. These findings show that mature erythrocytes can be generated from adult somatic cells, which may serve as an alternative source of RBCs for potential autologous transfusion.

  10. Mechanical stimulation of individual stereocilia of living cochlear hair cells by atomic force microscopy.

    Science.gov (United States)

    Langer, M G; Koitschev, A; Haase, H; Rexhausen, U; Hörber, J K; Ruppersberg, J P

    2000-02-01

    This paper describes the investigation of elastical properties and imaging of living cochlear hair bundles of inner (IHC) and outer hair cells (OHC) on the level of individual stereocilia. A custom-made AFM-setup was used, allowing to scan the mechano-sensitive structures of the inner ear under direct control of an upright differential interference contrast (DIC) microscope with a water-immersion objective. Scanning electron microscopy (SEM) images of the identical hair bundles obtained after AFM investigation demonstrated that forces up to 1.5 nanonewton (nN) did not cause obvious damage of the surface morphology of the stereocilia. These are the first images of hair bundles of living sensory cells of the organ of Corti by AFM. They display the tips of individual stereocilia and the typical V-shape of ciliary bundles. Since line scans clearly show that slope and force interaction depend on the elastical properties of stereocilia, quantitative stiffness measurements and stimulation of single transduction channels are suggested. PMID:10741679

  11. Molecular Properties and Pathophysiological Relevance of the Predominant K+ Conductance in Cochlear Outer Hair Cells

    OpenAIRE

    Leitner, Michael

    2012-01-01

    Cochlear outer hair cells (OHCs) are characterised by the voltage-dependent K+ conductance IK,n that previously was shown to be mediated by KCNQ4 (Kv7) channel subunits. IK,n/KCNQ4 dominates the electrical properties of the OHC cell membrane and furthermore is essential for OHC survival. Genetic deletion of KCNQ4 causes progressive degeneration of OHCs and deafness. Similarly, KCNQ4 loss-of-function mutations cause the progressive...

  12. Rhizobium sp. Degradation of Legume Root Hair Cell Wall at the Site of Infection Thread Origin

    OpenAIRE

    Ridge, Robert W.; Rolfe, Barry G.

    1985-01-01

    Using a new microinoculation technique, we demonstrated that penetration of Rhizobium sp. into the host root hair cell occurs at 20 to 22 h after inoculation. It did this by dissolving the cell wall maxtrix, leaving a layer of depolymerized wall microfibrils. Colony growth pressure “stretched” the weakened wall, forming a bulge into an interfacial zone between the wall and plasmalemma. At the same time vesicular bodies, similar to plasmalemmasomes, accumulated at the penetration site in a man...

  13. No Correlates for Somatic Motility in Freeze-Fractured Hair-Cell Membranes of Lizards and Birds

    Science.gov (United States)

    Köppl, C.; Forge, A.; Manley, G. A.

    2003-02-01

    It is not known whether active processes in mammals and non-mammals are due to the same underlying mechanism. To address this, we studied the size and density of particles in hair-cell membranes in mammals, in a lizard, the Tokay gecko, and in a bird, the barn owl. We surmised that if the prominent particles described in mammalian outer-hair-cell membranes are responsible for cochlear motility, a similar occurrence in non-mammalian hair cells would argue for similar mechanisms. Particle densities differed, however, substantially from those of mammals, suggesting that non-mammals have no membrane-based motility.

  14. Terapia génica como herramienta molecular para regenerar células ciliadas Genetic therapy as a molecular tool for hair cell regeneration

    Directory of Open Access Journals (Sweden)

    Juan Cristóbal Maass O

    2009-04-01

    Full Text Available La hipoacusia es un gran problema de salud pública. Un daño frecuente encontrado es la pérdida irreversible de las células ciliadas de la cóclea, con preservación de células de sostén, fenómeno común en mamíferos. Las terapias existentes no están orientadas a solucionar el problema de fondo. Trabajos muestran que se puede obtener regeneración ¡n vivo de células ciliadas y mejoría de los umbrales auditivos, mediante la sobrexpresión de Atohl en células de sostén del órgano de Corti (gen fundamental en desarrollo y diferenciación de células ciliadas. Existe evidencia experimental, de que la disminución de la expresión de genes con efecto opuesto puede estimular la proliferación y luego la transdiferenciación de células de sostén a células ciliadas. La investigación en este campo ayudará a entenderé! desarrollo y funcionamiento del oído interno en mamíferos y a que en el futuro se usen terapias de este tipo en pacientes sordos.Hearing loss is a major public health problem. A frequent type of damage, common in mammals, is the irreversible loss of cochlear hair cells, with preservation of the supporting cells. Current therapies are not oriented to solve the fundamental problem. The literature shows that In vivo regeneration of hair cells with auditory thresholds improvement is possible, using overexpression of Atohl (a key gene in the development and differentiation of hair cells in the organ of Corti supporting cells. Experimental evidence shows that a decrease in the expression of genes that have the opposite effect may stimulate proliferation and posterior differentiation of supporting cells into hair cells. Research on this field will contribute to our understanding of the development and functioning of the mammal inner ear, and to the future use of this type of therapeutic intervention in deaf patients.

  15. Squamous cell carcinoma in situ of the external auditory canal.

    Science.gov (United States)

    Shu, Min-Tsan; Lin, Hung-Ching; Yang, Cheng-Chien; Chang, Kuo-Ming

    2006-08-01

    We report two cases of carcinoma in situ in the external auditory canal (EAC), presenting with symptoms such as pain, long-term itching of the ear, easy contact bleeding, canal otorrhea and hearing loss. Otoscopic examination revealed granulation tissue and a greyish-black tumour with irregular surface. The first patient had previously been diagnosed with otitis externa with persistent ear itching for the past three years. The second patient had received tympanoplasty for treatment of chronic otitis media on the right ear ten years ago. The first case was treated with wide excision, whereas the second patient received resection of the skin of the EAC together with its adjacent soft tissue, followed by skin grafting. No tumour recurrence was noted in the fourth and third post-operative year for the first and second patient respectively. We suggest that EAC carcinoma can be detected early and treated. PMID:16719955

  16. Macrophage Recruitment and Epithelial Repair Following Hair Cell Injury in the Mouse Utricle

    Directory of Open Access Journals (Sweden)

    Edwin W Rubel

    2015-04-01

    Full Text Available The sensory organs of the inner ear possess resident populations of macrophages, but the function of those cells is poorly understood. In many tissues, macrophages participate in the removal of cellular debris after injury and can also promote tissue repair. The present study examined injury-evoked macrophage activity in the mouse utricle. Experiments used transgenic mice in which the gene for the human diphtheria toxin receptor (huDTR was inserted under regulation of the Pou4f3 promoter. Hair cells in such mice can be selectively lesioned by systemic treatment with diphtheria toxin (DT. In order to visualize macrophages, Pou4f3-huDTR mice were crossed with a second transgenic line, in which one or both copies of the gene for the fractalkine receptor CX3CR1 were replaced with a gene for GFP. Such mice expressed GFP in all macrophages, and mice that were CX3CR1GFP/GFP lacked the necessary receptor for fractalkine signaling. Treatment with DT resulted in the death of ~70% of utricular hair cells within seven days, which was accompanied by increased numbers of macrophages within the utricular sensory epithelium. Many of these macrophages appeared to be actively engulfing hair cell debris, indicating that macrophages participate in the process of ‘corpse removal’ in the mammalian vestibular organs. However, we observed no apparent differences in injury-evoked macrophage numbers in the utricles of CX3CR1+/GFP mice vs. CX3CR1GFP/GFP mice, suggesting that fractalkine signaling is not necessary for macrophage recruitment in these sensory organs. Finally, we found that repair of sensory epithelia at short times after DT-induced hair cell lesions was mediated by relatively thin cables of F-actin. After 56 days recovery, however, all cell-cell junctions were characterized by very thick actin cables.

  17. Corneal Limbal Microenvironment Can Induce Transdifferentiation of Hair Follicle Stem Cells into Corneal Epithelial-like Cells

    OpenAIRE

    Blazejewska, Ewa Anna; Schlötzer-Schrehardt, Ursula; Zenkel, Matthias; Bachmann, Björn; Chankiewitz, Erik; Jacobi, Christina; Kruse, Friedrich E.

    2009-01-01

    The aim of this study was to investigate the transdifferentiation potential of murine vibrissa hair follicle (HF) stem cells into corneal epithelial-like cells through modulation by corneal- or limbus-specific microenvironmental factors. Adult epithelial stem cells were isolated from the HF bulge region by mechanical dissection or fluorescence-activated cell sorting using antibodies to α6 integrin, enriched by clonal expansion, and subcultivated on various extracellular matrices (type IV coll...

  18. Cochlear Responses and Auditory Brainstem Response Functions in Adults with Auditory Neuropathy/ Dys-Synchrony and Individuals with Normal Hearing

    Directory of Open Access Journals (Sweden)

    Zahra Jafari

    2007-06-01

    Full Text Available Background and Aim: Physiologic measures of cochlear and auditory nerve function may be of assis¬tance in distinguishing between hearing disorders due primarily to auditory nerve impairment from those due primarily to cochlear hair cells dysfunction. The goal of present study was to measure of co-chlear responses (otoacoustic emissions and cochlear microphonics and auditory brainstem response in some adults with auditory neuropathy/ dys-synchrony and subjects with normal hearing. Materials and Methods: Patients were 16 adults (32 ears in age range of 14-30 years with auditory neu¬ropathy/ dys-synchrony and 16 individuals in age range of 16-30 years from both sexes. The results of transient otoacoustic emissions, cochlear microphonics and auditory brainstem response measures were compared in both groups and the effects of age, sex, ear and degree of hearing loss were studied. Results: The pure-tone average was 48.1 dB HL in auditory neuropathy/dys-synchrony group and the fre¬quency of low tone loss and flat audiograms were higher among other audiogram's shapes. Transient oto¬acoustic emissions were shown in all auditory neuropathy/dys-synchrony people except two cases and its average was near in both studied groups. The latency and amplitude of the biggest reversed co-chlear microphonics response were higher in auditory neuropathy/dys-synchrony patients than control peo¬ple significantly. The correlation between cochlear microphonics amplitude and degree of hearing loss was not significant, and age had significant effect in some cochlear microphonics measures. Audi-tory brainstem response had no response in auditory neuropathy/dys-synchrony patients even with low stim¬uli rates. Conclusion: In adults with speech understanding worsen than predicted from the degree of hearing loss that suspect to auditory neuropathy/ dys-synchrony, the frequency of low tone loss and flat audiograms are higher. Usually auditory brainstem response is absent in

  19. Multi-layered environmental regulation on the homeostasis of stem cells: the saga of hair growth and alopecia.

    Science.gov (United States)

    Chen, Chih-Chiang; Chuong, Cheng Ming

    2012-04-01

    Stem cells are fascinating because of their potential in regenerative medicine. Stem cell homeostasis has been thought to be mainly regulated by signals from their adjacent micro-environment named the "stem cell niche". However, recent studies reveal that there can be multiple layers of environmental controls. Here we review these environmental controls using the paradigm of hair stem cells, because to observe and analyze the growth of hair is easier due to their characteristic cyclic regeneration pattern. The length of hair fibers is regulated by the duration of the growth period. In the hair follicles, hair stem cells located in the follicle bulge interact with signals from the dermal papilla. Outside of the follicle, activation of hair stem cells has been shown to be modulated by molecules released from the intra-dermal adipose tissue as well as body hormone status, immune function, neural activities, and aging. The general physiological status of an individual is further influenced by circadian rhythms and changing seasons. The interactive networks of these environmental factors provide new understanding on how stem cell homeostasis is regulated, inspiring new insights for regenerative medicine. Therapies do not necessarily have to be achieved by using stem cells themselves which may constitute a higher risk but by modulating stem cell activity through targeting one or multiple layers of their micro- and macro-environments. PMID:22391240

  20. Photo-induced irreversible shortening and swelling of isolated cochlear outer hair cells

    International Nuclear Information System (INIS)

    In response to UVR with or without intracellular fura-2 and to blue light in the presence of BCECF (irradiation intensities of 2-12 x 105 W/m2) cochlear outer hair cells shortened and swelled within 15-30 s, accompanied by the formation of numerous cytoplasmic granulations. The cellular reactions were significantly delayed to 3 min by the addition of 1 mM of the radical scavengers p-phenylenediamine or n-propyl gallate. This protection suggests that free radicals, produced under UVR or under blue light irradiation in the presence of the sensitizer BCECF, are possible causative agents of this cell damage. The response of photo-damaged cells, namely shortening and increase in volume, resembled characteristics of hair cells exposed to an hypo-osmotic shock. This suggests that structural alterations of the cytoplasmic membrane and the sub-membrane cortex occurred under photo-irradiation, and that these structures can be implicated in the maintenance of the elongated cylindrical shape of the outer hair cells, possibly by maintaining intracellular hyperosmolarity. (author)

  1. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration.

    Science.gov (United States)

    Plikus, Maksim V; Mayer, Julie Ann; de la Cruz, Damon; Baker, Ruth E; Maini, Philip K; Maxson, Robert; Chuong, Cheng-Ming

    2008-01-17

    In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge are regulated by the surrounding microenvironment, or niche. The activation of such stem cells is cyclic, involving periodic beta-catenin activity. In the adult mouse, regeneration occurs in waves in a follicle population, implying coordination among adjacent follicles and the extrafollicular environment. Here we show that unexpected periodic expression of bone morphogenetic protein 2 (Bmp2) and Bmp4 in the dermis regulates this process. This BMP cycle is out of phase with the WNT/beta-catenin cycle, thus dividing the conventional telogen into new functional phases: one refractory and the other competent for hair regeneration, characterized by high and low BMP signalling, respectively. Overexpression of noggin, a BMP antagonist, in mouse skin resulted in a markedly shortened refractory phase and faster propagation of the regenerative wave. Transplantation of skin from this mutant onto a wild-type host showed that follicles in donor and host can affect their cycling behaviours mutually, with the outcome depending on the equilibrium of BMP activity in the dermis. Administration of BMP4 protein caused the competent region to become refractory. These results show that BMPs may be the long-sought 'chalone' inhibitors of hair growth postulated by classical experiments. Taken together, results presented in this study provide an example of hierarchical regulation of local organ stem cell homeostasis by the inter-organ macroenvironment. The expression of Bmp2 in subcutaneous adipocytes indicates physiological integration between these two thermo-regulatory organs. Our findings have practical importance for studies using mouse skin as a model for carcinogenesis, intra-cutaneous drug

  2. Inversion of Auditory Spectrograms, Traditional Spectrograms, and Other Envelope Representations

    DEFF Research Database (Denmark)

    Decorsière, Remi Julien Blaise; Søndergaard, Peter Lempel; MacDonald, Ewen;

    2015-01-01

    implementations of this framework are presented for auditory spectrograms, where the filterbank is based on the behavior of the basilar membrane and envelope extraction is modeled on the response of inner hair cells. One implementation is direct while the other is a two-stage approach that is computationally...... simpler. While both can accurately invert an auditory spectrogram, the two-stage approach performs better on time-domain metrics. The same framework is applied to traditional spectrograms based on the magnitude of the short-time Fourier transform. Inspired by human perception of loudness, a modification...

  3. Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome

    OpenAIRE

    Mohi Ahmed; Kiyoe Ura; Andrea Streit

    2015-01-01

    WHSC1 is a histone methyltransferase (HMT) that catalyses the addition of methyl groups to lysine 36 on histone 3. In humans, WHSC1 haploinsufficiency is associated with all known cases of Wolf-Hirschhorn syndrome (WHS). The cardinal feature of WHS is a craniofacial dysmorphism, which is accompanied by sensorineural hearing loss in 15% of individuals with WHS. Here, we show thatWHSC1-deficient mice display craniofacial defects that overlap with WHS, including cochlea anomalies. Although audit...

  4. A novel Atoh1 "self-terminating" mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability.

    Directory of Open Access Journals (Sweden)

    Ning Pan

    Full Text Available Atonal homolog1 (Atoh1 is a bHLH transcription factor essential for inner ear hair cell differentiation. Targeted expression of Atoh1 at various stages in development can result in hair cell differentiation in the ear. However, the level and duration of Atoh1 expression required for proper hair cell differentiation and maintenance remain unknown. We generated an Atoh1 conditional knockout (CKO mouse line using Tg(Atoh1-cre, in which the cre expression is driven by an Atoh1 enhancer element that is regulated by Atoh1 protein to "self-terminate" its expression. The mutant mice show transient, limited expression of Atoh1 in all hair cells in the ear. In the organ of Corti, reduction and delayed deletion of Atoh1 result in progressive loss of almost all the inner hair cells and the majority of the outer hair cells within three weeks after birth. The remaining cells express hair cell marker Myo7a and attract nerve fibers, but do not differentiate normal stereocilia bundles. Some Myo7a-positive cells persist in the cochlea into adult stages in the position of outer hair cells, flanked by a single row of pillar cells and two to three rows of disorganized Deiters cells. Gene expression analyses of Atoh1, Barhl1 and Pou4f3, genes required for survival and maturation of hair cells, reveal earlier and higher expression levels in the inner compared to the outer hair cells. Our data show that Atoh1 is crucial for hair cell mechanotransduction development, viability, and maintenance and also suggest that Atoh1 expression level and duration may play a role in inner vs. outer hair cell development. These genetically engineered Atoh1 CKO mice provide a novel model for establishing critical conditions needed to regenerate viable and functional hair cells with Atoh1 therapy.

  5. A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae.

    Science.gov (United States)

    Slowik, Amber D; Bermingham-McDonogh, Olivia

    2016-03-01

    The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled. PMID:26826497

  6. Auditory-model-based Feature Extraction Method for Mechanical Faults Diagnosis

    Institute of Scientific and Technical Information of China (English)

    LI Yungong; ZHANG Jinping; DAI Li; ZHANG Zhanyi; LIU Jie

    2010-01-01

    It is well known that the human auditory system possesses remarkable capabilities to analyze and identify signals. Therefore, it would be significant to build an auditory model based on the mechanism of human auditory systems, which may improve the effects of mechanical signal analysis and enrich the methods of mechanical faults features extraction. However the existing methods are all based on explicit senses of mathematics or physics, and have some shortages on distinguishing different faults, stability, and suppressing the disturbance noise, etc. For the purpose of improving the performances of the work of feature extraction, an auditory model, early auditory(EA) model, is introduced for the first time. This auditory model transforms time domain signal into auditory spectrum via bandpass filtering, nonlinear compressing, and lateral inhibiting by simulating the principle of the human auditory system. The EA model is developed with the Gammatone filterbank as the basilar membrane. According to the characteristics of vibration signals, a method is proposed for determining the parameter of inner hair cells model of EA model. The performance of EA model is evaluated through experiments on four rotor faults, including misalignment, rotor-to-stator rubbing, oil film whirl, and pedestal looseness. The results show that the auditory spectrum, output of EA model, can effectively distinguish different faults with satisfactory stability and has the ability to suppress the disturbance noise. Then, it is feasible to apply auditory model, as a new method, to the feature extraction for mechanical faults diagnosis with effect.

  7. Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation.

    Science.gov (United States)

    Chen, J-R; Tang, Z-H; Zheng, J; Shi, H-S; Ding, J; Qian, X-D; Zhang, C; Chen, J-L; Wang, C-C; Li, L; Chen, J-Z; Yin, S-K; Shao, J-Z; Huang, T-S; Chen, P; Guan, M-X; Wang, J-F

    2016-08-01

    Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction. PMID:26915297

  8. Hair Care

    Science.gov (United States)

    ... Body Looking and feeling your best Hair care Hair care Short, long, curly, straight, up, down. Hair options can seem endless! Not all of what makes your hair look good comes from the outside, though. Good ...

  9. Oily hair

    Science.gov (United States)

    Hair - oily ... are some tips for preventing and treating oily hair: Shampoo your hair every day. Leaving the shampoo on your head ... minutes before rinsing may help. Avoid brushing your hair too often or too vigorously, since the brushing ...

  10. A theoretical model for ROP localisation by auxin in Arabidopsis root hair cells.

    Directory of Open Access Journals (Sweden)

    Robert J H Payne

    Full Text Available Local activation of Rho GTPases is important for many functions including cell polarity, morphology, movement, and growth. Although a number of molecules affecting Rho-of-Plants small GTPase (ROP signalling are known, it remains unclear how ROP activity becomes spatially organised. Arabidopsis root hair cells produce patches of ROP at consistent and predictable subcellular locations, where root hair growth subsequently occurs.We present a mathematical model to show how interaction of the plant hormone auxin with ROPs could spontaneously lead to localised patches of active ROP via a Turing or Turing-like mechanism. Our results suggest that correct positioning of the ROP patch depends on the cell length, low diffusion of active ROP, a gradient in auxin concentration, and ROP levels. Our theory provides a unique explanation linking the molecular biology to the root hair phenotypes of multiple mutants and transgenic lines, including OX-ROP, CA-rop, aux1, axr3, tip1, eto1, etr1, and the triple mutant aux1 ein2 gnom(eb.We show how interactions between Rho GTPases (in this case ROPs and regulatory molecules (in this case auxin could produce characteristic subcellular patterning that subsequently affects cell shape. This has important implications for research on the morphogenesis of plants and other eukaryotes. Our results also illustrate how gradient-regulated Turing systems provide a particularly robust and flexible mechanism for pattern formation.

  11. Calcium imaging of inner ear hair cells within the cochlear epithelium of mice using two-photon microscopy

    OpenAIRE

    Yuan, Tao; Gao, Simon S.; Saggau, Peter; OGHALAI, JOHN S

    2010-01-01

    Mice are an excellent model for studying mammalian hearing and transgenic mouse models of human hearing, loss are commonly available. However, the mouse cochlea is substantially smaller than other animal models routinely used to study cochlear physiology. This makes study of their hair cells difficult. We develop a novel methodology to optically image calcium within living hair cells left undisturbed within the excised mouse cochlea. Fresh cochleae are harvested, left intact within their otic...

  12. From Zebrafish to Mammal: Functional Evolution of Prestin, the Motor Protein of Cochlear Outer Hair Cells

    OpenAIRE

    Tan, Xiaodong; Pecka, Jason L.; Tang, Jie; Okoruwa, Oseremen E.; Zhang, Qian; Beisel, Kirk W.; He, David Z.Z.

    2010-01-01

    Prestin is the motor protein of cochlear outer hair cells. It belongs to a distinct anion transporter family called solute carrier protein 26A, or SLC26A. Members of this family serve two fundamentally distinct functions. Although most members transport different anion substrates across a variety of epithelia, prestin (SLC26A5) is unique, functioning as a voltage-dependent motor protein. Recent evidence suggests that prestin orthologs from zebrafish and chicken are electrogenic divalent/chlor...

  13. Evidence for Outer Hair Cell Driven Oscillatory Fluid Flow in the Tunnel of Corti

    OpenAIRE

    Karavitaki, K. Domenica; Mountain, David C.

    2007-01-01

    Outer hair cell (OHC) somatic motility plays a key role in mammalian cochlear frequency selectivity and hearing sensitivity, but the mechanism of cochlear amplification is not well understood and remains a matter of controversy. We have visualized and quantified the effects of electrically evoked OHC somatic motility within the gerbil organ of Corti using an excised cochlear preparation. We found that OHC motility induces oscillatory motion of the medial olivocochlear fibers where they cross ...

  14. Calcium-dependent synaptic vesicle trafficking underlies indefatigable release at the hair cell afferent fiber synapse

    OpenAIRE

    Schnee, M.E.; Santos-Sacchi, J; Castellano-Muñoz, M.; Kong, J-H.; Ricci, A.J.

    2011-01-01

    Sensory hair cell ribbon synapses respond to graded stimulation in a linear, indefatigable manner, requiring that vesicle trafficking to synapses is rapid and non rate limiting. Real time monitoring of vesicle fusion identified two release components. The first was saturable with both release rate and magnitude varying linearly with Ca2+, however the magnitude was too small to account for sustained afferent firing rates. A second superlinear release component required recruitment, in a Ca2+-d...

  15. Advances in a Rapidly Emerging Field of Hair Follicle Stem Cell Research

    OpenAIRE

    Bukvić Mokos, Zrinka; Lazić Mosler, Elvira

    2014-01-01

    Human skin maintains the ability to regenerate during adulthood, as it constantly renews itself throughout adult life, and the hair follicle (HF) undergoes a perpetual cycle of growth and degeneration. The study of stem cells (SCs) in the epidermis and skin tissue engineering is a rapidly emerging field, where advances have been made in both basic and clinical research. Advances in basic science include the ability to assay SCs of the epidermis in vivo, identification of an independent interf...

  16. Growth factor treatment enhances vestibular hair cell renewal and results in improved vestibular function

    OpenAIRE

    Kopke, Richard D; Jackson, Ronald L; Li, Geming; Rasmussen, Mark D.; Hoffer, Michael E.; Frenz, Dorothy A.; Costello, Michael; Schultheiss, Peter; Van De Water, Thomas R.

    2001-01-01

    The vestibules of adult guinea pigs were lesioned with gentamicin and then treated with perilymphatic infusion of either of two growth factor mixtures (i.e., GF I or GF II). GF I contained transforming growth factor α (TGFα), insulin-like growth factor type one (IGF-1), and retinoic acid (RA), whereas GF II contained those three factors and brain-derived neurotrophic factor. Treatment with GF I significantly enhanced vestibular hair cell renewal in ototoxin-damaged ...

  17. Functional Features of Trans-differentiated Hair Cells Mediated by Atoh1 Reveals a Primordial Mechanism

    OpenAIRE

    Yang, Juanmei; Bouvron, Sonia; Lv, Ping; Chi, Fanglu; Yamoah, Ebenezer N.

    2012-01-01

    Evolution has transformed a simple ear with few vestibular maculae into a complex 3-dimensional structure consisting of nine distinct endorgans. It is debatable whether the sensory epithelia underwent progressive segregation or emerged from distinct sensory patches. To address these uncertainties we examined the morphological and functional phenotype of trans-differentiated rat hair cells to reveal their primitive or endorgan-specific origins. Additionally, it is uncertain how Atoh1-mediated ...

  18. Glucose transporter 5 is undetectable in outer hair cells and does not contribute to cochlear amplification

    OpenAIRE

    Wu, Xudong; Wang, Xiang; Gao, Jiangang; Yu, Yiling; Jia, Shuping; Zheng, Jing; Dallos, Peter; David Z Z He; Cheatham, Mary Ann; Zuo, Jian

    2008-01-01

    Glucose transporter 5 (Glut5) is a high-affinity fructose transporter. It was proposed to be a motor protein or part of the motor complex required for cochlear amplification in outer hair cells (OHCs). Here we show that, in contrast to previous reports, Glut5 is undetectable, and possibly absent, in OHCs harvested from wildtype mice. Further, Glut5-deficient mice display normal OHC morphology and motor function (i.e., nonlinear capacitance and electromotility) and normal cochlear sensitivity....

  19. Spontaneous hair cell regeneration in the mouse utricle following gentamicin ototoxicity

    OpenAIRE

    Kawamoto, Kohei; Izumikawa, Masahiko; Lisa A. Beyer; Atkin, Graham M.; Raphael, Yehoash

    2008-01-01

    Whereas most epithelial tissues turn-over and regenerate after a traumatic lesion, this restorative ability is diminished in the sensory epithelia of the inner ear; it is absent in the cochlea and exists only in a limited capacity in the vestibular epithelium. The extent of regeneration in vestibular hair cells has been characterized for several mammalian species including guinea pig, rat, and chinchilla, but not yet in mouse. As the fundamental model species for investigating hereditary dise...

  20. Cochlear Outer-Hair-Cell Power Generation and Viscous Fluid Loss

    OpenAIRE

    Yanli Wang; Steele, Charles R.; Sunil Puria

    2016-01-01

    Since the discovery of otoacoustic emissions and outer hair cell (OHC) motility, the fundamental question of whether the cochlea produces mechanical power remains controversial. In the present work, direct calculations are performed on power loss due to fluid viscosity and power generated by the OHCs. A three-dimensional box model of the mouse cochlea is used with a feed-forward/feed-backward approximation representing the organ of Corti cytoarchitecture. The model is fit to in vivo basilar m...

  1. Actuation of flexoelectric membranes in viscoelastic fluids with applications to outer hair cells

    OpenAIRE

    Herrera-Valencia, E. E.; Rey, Alejandro D.

    2014-01-01

    Liquid crystal flexoelectric actuation uses an imposed electric field to create membrane bending, and it is used by the outer hair cells (OHCs) located in the inner ear, whose role is to amplify sound through generation of mechanical power. Oscillations in the OHC membranes create periodic viscoelastic flows in the contacting fluid media. A key objective of this work on flexoelectric actuation relevant to OHCs is to find the relations and impact of the electromechanical properties of the memb...

  2. Analysis of Dermal Papilla Cell Interactome Using STRING Database to Profile the ex Vivo Hair Growth Inhibition Effect of a Vinca Alkaloid Drug, Colchicine

    OpenAIRE

    Ching-Wu Hsia; Ming-Yi Ho; Hao-Ai Shui; Chong-Bin Tsai; Min-Jen Tseng

    2015-01-01

    Dermal papillae (DPs) control the formation of hair shafts. In clinical settings, colchicine (CLC) induces patients’ hair shedding. Compared to the control, the ex vivo hair fiber elongation of organ cultured vibrissa hair follicles (HFs) declined significantly after seven days of CLC treatment. The cultured DP cells (DPCs) were used as the experimental model to study the influence of CLC on the protein dynamics of DPs. CLC could alter the morphology and down-regulate the expression of alkal...

  3. Transcriptome Sequencing Reveals Differences between Primary and Secondary Hair Follicle-derived Dermal Papilla Cells of the Cashmere Goat (Capra hircus)

    OpenAIRE

    Bing Zhu; Teng Xu; Jianlong Yuan; Xudong Guo; Dongjun Liu

    2013-01-01

    The dermal papilla is thought to establish the character and control the size of hair follicles. Inner Mongolia Cashmere goats (Capra hircus) have a double coat comprising the primary and secondary hair follicles, which have dramatically different sizes and textures. The Cashmere goat is rapidly becoming a potent model for hair follicle morphogenesis research. In this study, we established two dermal papilla cell lines during the anagen phase of the hair growth cycle from the primary and seco...

  4. Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death.

    Directory of Open Access Journals (Sweden)

    Kelly N Owens

    2008-02-01

    Full Text Available Inner ear sensory hair cell death is observed in the majority of hearing and balance disorders, affecting the health of more than 600 million people worldwide. While normal aging is the single greatest contributor, exposure to environmental toxins and therapeutic drugs such as aminoglycoside antibiotics and antineoplastic agents are significant contributors. Genetic variation contributes markedly to differences in normal disease progression during aging and in susceptibility to ototoxic agents. Using the lateral line system of larval zebrafish, we developed an in vivo drug toxicity interaction screen to uncover genetic modulators of antibiotic-induced hair cell death and to identify compounds that confer protection. We have identified 5 mutations that modulate aminoglycoside susceptibility. Further characterization and identification of one protective mutant, sentinel (snl, revealed a novel conserved vertebrate gene. A similar screen identified a new class of drug-like small molecules, benzothiophene carboxamides, that prevent aminoglycoside-induced hair cell death in zebrafish and in mammals. Testing for interaction with the sentinel mutation suggests that the gene and compounds may operate in different pathways. The combination of chemical screening with traditional genetic approaches is a new strategy for identifying drugs and drug targets to attenuate hearing and balance disorders.

  5. Stochastic resonance in the synaptic transmission between hair cells and vestibular primary afferents in development.

    Science.gov (United States)

    Flores, A; Manilla, S; Huidobro, N; De la Torre-Valdovinos, B; Kristeva, R; Mendez-Balbuena, I; Galindo, F; Treviño, M; Manjarrez, E

    2016-05-13

    The stochastic resonance (SR) is a phenomenon of nonlinear systems in which the addition of an intermediate level of noise improves the response of such system. Although SR has been studied in isolated hair cells and in the bullfrog sacculus, the occurrence of this phenomenon in the vestibular system in development is unknown. The purpose of the present study was to explore for the existence of SR via natural mechanical-stimulation in the hair cell-vestibular primary afferent transmission. In vitro experiments were performed on the posterior semicircular canal of the chicken inner ear during development. Our experiments showed that the signal-to-noise ratio of the afferent multiunit activity from E15 to P5 stages of development exhibited the SR phenomenon, which was characterized by an inverted U-like response as a function of the input noise level. The inverted U-like graphs of SR acquired their higher amplitude after the post-hatching stage of development. Blockage of the synaptic transmission with selective antagonists of the NMDA and AMPA/Kainate receptors abolished the SR of the afferent multiunit activity. Furthermore, computer simulations on a model of the hair cell - primary afferent synapse qualitatively reproduced this SR behavior and provided a possible explanation of how and where the SR could occur. These results demonstrate that a particular level of mechanical noise on the semicircular canals can improve the performance of the vestibular system in their peripheral sensory processing even during embryonic stages of development. PMID:26926966

  6. Noise alters hair-bundle mechanics at the cochlear apex

    Science.gov (United States)

    Strimbu, C. Elliott; Fridberger, Anders

    2015-12-01

    Exposure to loud sounds can lead to both permanent and short term changes in auditory sensitivity. Permanent hearing loss is often associated with gross changes in cochlear morphology including the loss of hair cells and auditory nerve fibers while the mechanisms of short term threshold shifts are much less well understood and may vary at different locations across the cochlea. Previous reports suggest that exposure to loud sounds leads to a decrease in the cochlear microphonic potential and in the stiffness of the organ of Corti. Because the cochlear microphonic reflects changes in the membrane potential of the hair cells, this suggests that hair-bundle motion should be reversibly altered following exposure to loud sounds. Using an in vitro preparation of the guinea pig temporal bone we investigate changes in the micro-mechanical response near the cochlear apex following a brief (up to 10 - 20 minutes) exposure to loud (˜ 120 dB) tones near the best frequency at this location. We use time-resolved confocal imaging to record the motion of outer hair cell bundles before and after acoustic overstimulation. We have also recorded larger-scale structural views of the organ of Corti before and after exposure to the loud sound. Conventional electrophysiological techniques are used measure the cochlear microphonic potential. As has been previously reported, following acoustic overexposure the cochlear microphonic declines in value and typically recovers on the order of 30 - 60 minutes. Hair-bundle trajectories are affected following the loud sound and typically recover on a somewhat faster time scale than the microphonic potential, although the results vary considerably across preparations. Preliminary results also suggest reversible changes in the hair cell's resting potential following the loud sound.

  7. Behavior of Primary Cilia and Tricellular Tight Junction Proteins during Differentiation in Temperature-Sensitive Mouse Cochlear Precursor Hair Cells.

    Science.gov (United States)

    Kakuki, Takuya; Kaneko, Yakuto; Takano, Kenichi; Ninomiya, Takafumi; Kohno, Takayuki; Kojima, Takashi; Himi, Tetsuo

    2016-01-01

    In the sensory hair cells of the mammalian cochlea, the primary cilia in the planar cell polarity as well as the tight junctions in the epithelial cell polarity and the barrier are important to maintain normal hearing. Temperature-sensitive mouse cochlear precursor hair cells were used to investigate the behavior of primary cilia and tricellular tight junction proteins during the differentiation of sensory hair cells. In undifferentiated cells (incubated at 33°C), many acetylated tubulin-positive primary cilia were observed, and each was accompanied with an x03B3;-tubulin-positive basal body. The primary cilia had a '9 + 0' architecture with nine outer microtubule doublets but lacking a central pair of microtubules. In differentiated cells (incubated at 39°C), acetylated tubulin-positive primary cilia as well as acetylated tubulin-positive cilia-like structures were partially observed on the cell surface. In differentiated cells, the number of primary cilia was markedly reduced compared with undifferentiated cells, and innumerable cilia-like structures with no ciliary pockets were partially observed on the cell surface. In undifferentiated cells, few tricellulin molecules and lipolysis-stimulated lipoprotein receptors (LSRs) were observed in the cytoplasm. In differentiated cells, many tricellulin molecules and LSRs were observed on the membranes and within the cytoplasm. Conditional immortalized mouse cochlear precursor hair cells may be useful to investigate the roles of primary cilia and tricellular tight junctions during cellular differentiation and degeneration such as apoptosis. PMID:27115742

  8. In vivo and in vitro biophysical properties of hair cells from the lateral line and inner ear of developing and adult zebrafish

    OpenAIRE

    Olt, J; Johnson, S. L.; Marcotti, W.

    2014-01-01

    Hair cells detect and process sound and movement information, and transmit this with remarkable precision and efficiency to afferent neurons via specialized ribbon synapses. The zebrafish is emerging as a powerful model for genetic analysis of hair cell development and function both in vitro and in vivo. However, the full exploitation of the zebrafish is currently limited by the difficulty in performing systematic electrophysiological recordings from hair cells under physiological recording c...

  9. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth.

    Science.gov (United States)

    Higgins, Claire A; Chen, James C; Cerise, Jane E; Jahoda, Colin A B; Christiano, Angela M

    2013-12-01

    De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

  10. miR-21 promotes the differentiation of hair follicle-derived neural crest stem cells into Schwann cells

    Institute of Scientific and Technical Information of China (English)

    Yuxin Ni; Kaizhi Zhang; Xuejuan Liu; Tingting Yang; Baixiang Wang; Li Fu; Lan A; Yanmin Zhou

    2014-01-01

    Hair follicle-derived neural crest stem cells can be induced to differentiate into Schwann cells in vivo and in vitro. However, the underlying regulatory mechanism during cell differentiation remains poorly understood. This study isolated neural crest stem cells from human hair folli-cles and induced them to differentiate into Schwann cells. Quantitative RT-PCR showed that microRNA (miR)-21 expression was gradually increased during the differentiation of neural crest stem cells into Schwann cells. After transfection with the miR-21 agonist (agomir-21), the differentiation capacity of neural crest stem cells was enhanced. By contrast, after transfection with the miR-21 antagonist (antagomir-21), the differentiation capacity was attenuated. Further study results showed that SOX-2 was an effective target of miR-21. Without compromising SOX2 mRNA expression, miR-21 can down-regulate SOX protein expression by binding to the 3′-UTR of miR-21 mRNA. Knocking out the SOX2 gene from the neural crest stem cells significantly reversed the antagomir-21 inhibition of neural crest stem cells differentiating into Schwann cells. The results suggest that miR-21 expression was increased during the differentiation of neural crest stem cells into Schwann cells and miR-21 promoted the differentiation through down-regu-lating SOX protein expression by binding to the 3′-UTR of SOX2 mRNA.

  11. A Case of Basal Cell Carcinoma with Outer Hair Follicle Sheath Differentiation.

    Science.gov (United States)

    Onishi, Masazumi; Takahashi, Kazuhiro; Maeda, Fumihiko; Akasaka, Toshihide

    2015-01-01

    A 70-year-old Japanese man presented at our hospital with an asymptomatic, blackish, irregularly shaped plaque with a gray nodule in the periphery on his left lower leg. The lesion had been present for 10 years and had recently enlarged, associated with bleeding. Histopathologically, the tumor consisted of three distinct parts: The first part showed massive aggregation of basophilic basaloid cells with peripheral palisading and abundant melanin granules, and was diagnosed as solid-type basal cell carcinoma. The second part showed aggregation of clear cells with squamous eddies, and was diagnosed as proliferating trichilemmal tumor. The third part showed reticular aggregation of basaloid cells with infundibular cysts in the papillary dermis, and was diagnosed as infundibulocystic basal cell carcinoma. We diagnosed this tumor as basal cell carcinoma with various forms of hair follicle differentiation, including differentiation into the outer root sheath. PMID:26955331

  12. A Case of Basal Cell Carcinoma with Outer Hair Follicle Sheath Differentiation

    Directory of Open Access Journals (Sweden)

    Masazumi Onishi

    2015-12-01

    Full Text Available A 70-year-old Japanese man presented at our hospital with an asymptomatic, blackish, irregularly shaped plaque with a gray nodule in the periphery on his left lower leg. The lesion had been present for 10 years and had recently enlarged, associated with bleeding. Histopathologically, the tumor consisted of three distinct parts: The first part showed massive aggregation of basophilic basaloid cells with peripheral palisading and abundant melanin granules, and was diagnosed as solid-type basal cell carcinoma. The second part showed aggregation of clear cells with squamous eddies, and was diagnosed as proliferating trichilemmal tumor. The third part showed reticular aggregation of basaloid cells with infundibular cysts in the papillary dermis, and was diagnosed as infundibulocystic basal cell carcinoma. We diagnosed this tumor as basal cell carcinoma with various forms of hair follicle differentiation, including differentiation into the outer root sheath.

  13. A new Atp2b2 deafwaddler allele, dfwi5, interacts strongly with Cdh23 and other auditory modifiers

    OpenAIRE

    Watson, Claire J.; Tempel, Bruce L

    2013-01-01

    Tight regulation of calcium (Ca2+) concentrations in the stereocilia bundles of auditory hair cells of the inner ear is critical to normal auditory transduction. The plasma membrane Ca2+ ATPase 2 (PMCA2), encoded by the Atp2b2 gene, is the primary mechanism for clearance of Ca2+ from auditory stereocilia, keeping intracellular levels low, and also contributes to maintaining adequate levels of extracellular Ca2+ in the endolymph. This study characterizes a novel null Atp2b2 allele, dfwi5, by e...

  14. Transcriptome sequencing reveals differences between primary and secondary hair follicle-derived dermal papilla cells of the Cashmere goat (Capra hircus.

    Directory of Open Access Journals (Sweden)

    Bing Zhu

    Full Text Available The dermal papilla is thought to establish the character and control the size of hair follicles. Inner Mongolia Cashmere goats (Capra hircus have a double coat comprising the primary and secondary hair follicles, which have dramatically different sizes and textures. The Cashmere goat is rapidly becoming a potent model for hair follicle morphogenesis research. In this study, we established two dermal papilla cell lines during the anagen phase of the hair growth cycle from the primary and secondary hair follicles and clarified the similarities and differences in their morphology and growth characteristics. High-throughput transcriptome sequencing was used to identify gene expression differences between the two dermal papilla cell lines. Many of the differentially expressed genes are involved in vascularization, ECM-receptor interaction and Wnt/β-catenin/Lef1 signaling pathways, which intimately associated with hair follicle morphogenesis. These findings provide valuable information for research on postnatal morphogenesis of hair follicles.

  15. Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2

    OpenAIRE

    Furness, David N.; Johnson, Stuart L.; Manor, Uri; Rüttiger, Lukas; Tocchetti, Arianna; Offenhauser, Nina; Olt, Jennifer; Goodyear, Richard J.; Vijayakumar, Sarath; Dai, Yuhai; Hackney, Carole M.; Franz, Christoph; Di Fiore, Pier Paolo; Masetto, Sergio; Jones, Sherri M.

    2013-01-01

    Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during development and in the adult. We show that the actin-binding protein epidermal growth factor receptor pathway substrate 8 (Eps8)L2, a member of the Eps8-like protein family, is a newly i...

  16. Calcium imaging of inner ear hair cells within the cochlear epithelium of mice using two-photon microscopy

    Science.gov (United States)

    Yuan, Tao; Gao, Simon S.; Saggau, Peter; Oghalai, John S.

    2010-01-01

    Mice are an excellent model for studying mammalian hearing and transgenic mouse models of human hearing, loss are commonly available. However, the mouse cochlea is substantially smaller than other animal models routinely used to study cochlear physiology. This makes study of their hair cells difficult. We develop a novel methodology to optically image calcium within living hair cells left undisturbed within the excised mouse cochlea. Fresh cochleae are harvested, left intact within their otic capsule bone, and fixed in a recording chamber. The bone overlying the cochlear epithelium is opened and Reissner's membrane is incised. A fluorescent calcium indicator is applied to the preparation. A custom-built upright two-photon microscope was used to image the preparation using 3-D scanning. We are able to image about one third of a cochlear turn simultaneously, in either the apical or basal regions. Within one hour of animal sacrifice, we find that outer hair cells demonstrate increased fluorescence compared with surrounding supporting cells. This methodology is then used to visualize hair cell calcium changes during mechanotransduction over a region of the epithelium. Because the epithelium is left within the cochlea, dissection trauma is minimized and artifactual changes in hair cell physiology are expected to be reduced.

  17. Both pre- and postsynaptic activity of Nsf prevents degeneration of hair-cell synapses.

    Directory of Open Access Journals (Sweden)

    Weike Mo

    Full Text Available Vesicle fusion contributes to the maintenance of synapses in the nervous system by mediating synaptic transmission, release of neurotrophic factors, and trafficking of membrane receptors. N-ethylmaleimide-sensitive factor (NSF is indispensible for dissociation of the SNARE-complex following vesicle fusion. Although NSF function has been characterized extensively in vitro, the in vivo role of NSF in vertebrate synaptogenesis is relatively unexplored. Zebrafish possess two nsf genes, nsf and nsfb. Here, we examine the function of either Nsf or Nsfb in the pre- and postsynaptic cells of the zebrafish lateral line organ and demonstrate that Nsf, but not Nsfb, is required for maintenance of afferent synapses in hair cells. In addition to peripheral defects in nsf mutants, neurodegeneration of glutamatergic synapses in the central nervous system also occurs in the absence of Nsf function. Expression of an nsf transgene in a null background indicates that stabilization of synapses requires Nsf function in both hair cells and afferent neurons. To identify potential targets of Nsf-mediated fusion, we examined the expression of genes implicated in stabilizing synapses and found that transcripts for multiple genes including brain-derived neurotrophic factor (bdnf were significantly reduced in nsf mutants. With regard to trafficking of BDNF, we observed a striking accumulation of BDNF in the neurites of nsf mutant afferent neurons. In addition, injection of recombinant BDNF protein partially rescued the degeneration of afferent synapses in nsf mutants. These results establish a role for Nsf in the maintenance of synaptic contacts between hair cells and afferent neurons, mediated in part via the secretion of trophic signaling factors.

  18. Hair cell-type dependent expression of basolateral ion channels shapes response dynamics in the frog utricle

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    Alessandro eVenturino

    2015-09-01

    Full Text Available The dynamics of vestibular afferent responses are thought to be strongly influenced by presynaptic properties. In this paper, by performing whole-cell perforated-patch experiments in the frog utricle, we characterized voltage-dependent currents and voltage responses to current steps and 0.3-100 Hz sinusoids. Current expression and voltage responses are strongly related to hair cell type. In particular, voltage responses of extrastriolar type eB (low pass, -3 dB corner at 52.512.8 Hz and striolar type F cells (resonant, tuned at 6046 Hz agree with the dynamics (tonic and phasic, respectively of the afferent fibers they contact. On the other hand, hair cell release (measured with single-sine membrane Cm measurements was linearly related to Ca in both cell types, and therefore did not appear to contribute to dynamics differences. As a tool for quantifying the relative contribution of basolateral currents and other presynaptic factors to afferent dynamics, the recorded current, voltage and release data were used to build a NEURON model of the average extrastriolar type eB and striolar type F hair cell. The model contained all recorded conductances, a basic mechanosensitive hair bundle and a ribbon synapse sustained by stochastic voltage-dependent Ca channels, and could reproduce the recorded hair cell voltage responses. Simulated release obtained from eB-type and F-type models display significant differences in dynamics, supporting the idea that basolateral currents are able to contribute to afferent dynamics; however, release in type eB and F cell models does not reproduce tonic and phasic dynamics, mainly because of an excessive phase lag present in both cell types. This suggests the presence in vestibular hair cells of an additional, phase-advancing mechanism, in cascade with voltage modulation.

  19. Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes’ hearing problem: an innovation in multi-channel-array skin-hearing technology

    OpenAIRE

    Li, Jianwen; Li, Yan; Zhang, Ming; Ma, Weifang; Ma, Xuezong

    2014-01-01

    The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different...

  20. Intravital imaging of hair-cell development and regeneration in the zebrafish

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    Hernan Lopez-Schier

    2013-10-01

    Full Text Available Direct videomicroscopic visualization of organ formation and regeneration in toto is a powerful strategy to study cellular processes that often cannot be replicated in vitro. Intravital imaging aims at quantifying changes in tissue architecture or subcellular organization over time during organ development, regeneration or degeneration. A general feature of this approach is its reliance on the optical isolation of defined cell types in the whole animals by transgenic expression of fluorescent markers. Here we describe a simple and robust method to analyze sensory hair-cell development and regeneration in the zebrafish lateral line by high-resolution intravital imaging using laser-scanning confocal microscopy (LSCM and selective plane illumination microscopy (SPIM. The main advantage of studying hair-cell regeneration in the lateral line is that it occurs throughout the life of the animal, which allows its study in the most natural context. We detail protocols to achieve continuous videomicroscopy for up to 68 hours, enabling direct observation of cellular behavior, which can provide a sensitive assay for the quantitative classification of cellular phenotypes and cell-lineage reconstruction. Modifications to this protocol should facilitate pharmacogenetic assays to identify or validate otoprotective or reparative drugs for future clinical strategies aimed at preserving aural function in humans.

  1. Hair transplant

    Science.gov (United States)

    Hair restoration ... Avram MR, Keene SA, Stough DB, Rogers NE. Hair restoration. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. ... PA: Elsevier Saunders; 2012:chap 157. Fisher J. Hair restoration. In: Neligan PC, ed. Plastic Surgery . 3rd ed. ...

  2. Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

    Science.gov (United States)

    Cochran, S. L.

    1995-01-01

    The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the

  3. Stem cells, transcription factors and apoptosis related molecules in hair follicle development and maintenance

    Czech Academy of Sciences Publication Activity Database

    Veselá, Barbora; Matalová, Eva

    Brno : VFU Brno, 2012. 23-25. ISBN 978-80-7305-620-9. [Konference mladých vědeckých pracovníků s mezinárodní účastí 2012 na FVL VFU Brno. 30.05.2012-30.05.2012, Brno] R&D Projects: GA ČR(CZ) GAP502/12/1285 Institutional research plan: CEZ:AV0Z50450515 Keywords : hair follicles Subject RIV: EA - Cell Biology

  4. Whirler Mutant Hair Cells Have Less Severe Pathology than Shaker 2 or Double Mutants

    OpenAIRE

    Mustapha, Mirna; Lisa A. Beyer; Izumikawa, Masahiko; Swiderski, Donald L.; Dolan, David F.; Raphael, Yehoash; Camper, Sally A.

    2007-01-01

    MYOSIN XV is a motor protein that interacts with the PDZ domain-containing protein WHIRLIN and transports WHIRLIN to the tips of the stereocilia. Shaker 2 (sh2) mice have a mutation in the motor domain of MYOSIN XV and exhibit congenital deafness and circling behavior, probably because of abnormally short stereocilia. Whirler (wi) mice have a similar phenotype caused by a deletion in the third PDZ domain of WHIRLIN. We compared the morphology of Whrnwi/wi and Myo15sh2/sh2 sensory hair cells a...

  5. Expression of EFR3A in the Mouse Cochlea during Degeneration of Spiral Ganglion following Hair Cell Loss

    OpenAIRE

    Nie, Chen; Hu, Haixia; Shen, Chenling; Ye, Bin; Wu, Hao; Xiang, Mingliang

    2015-01-01

    Retrograde degeneration of spiral ganglion cells in the cochlea following hair cell loss is similar to dying back in pathology. The EFR3A gene has recently been discovered to be involved in the pathogenesis of dying back. The relationship of EFR3A and spiral ganglion degeneration, however, was rarely investigated. In this study, we destroyed the hair cells of the mouse cochlea by co-administration of kanamycin and furosemide and then investigated the EFR3A expression during the induced spiral...

  6. Hair-Growth-Promoting Effect of Conditioned Medium of High Integrin α6 and Low CD 71 (α6bri/CD71dim) Positive Keratinocyte Cells

    OpenAIRE

    Chong Hyun Won; Yun-Mi Jeong; Sangjin Kang; Tae-Sung Koo; So-Hyun Park; Ki-Young Park; Young-Kwan Sung; Jong-Hyuk Sung

    2015-01-01

    Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly...

  7. Live imaging the phagocytic activity of inner ear supporting cells in response to hair cell death.

    Science.gov (United States)

    Monzack, E L; May, L A; Roy, S; Gale, J E; Cunningham, L L

    2015-12-01

    Hearing loss and balance disorders affect millions of people worldwide. Sensory transduction in the inner ear requires both mechanosensory hair cells (HCs) and surrounding glia-like supporting cells (SCs). HCs are susceptible to death from aging, noise overexposure, and treatment with therapeutic drugs that have ototoxic side effects; these ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic drug cisplatin. Although both classes of drugs are known to kill HCs, their effects on SCs are less well understood. Recent data indicate that SCs sense and respond to HC stress, and that their responses can influence HC death, survival, and phagocytosis. These responses to HC stress and death are critical to the health of the inner ear. Here we have used live confocal imaging of the adult mouse utricle, to examine the SC responses to HC death caused by aminoglycosides or cisplatin. Our data indicate that when HCs are killed by aminoglycosides, SCs efficiently remove HC corpses from the sensory epithelium in a process that includes constricting the apical portion of the HC after loss of membrane integrity. SCs then form a phagosome, which can completely engulf the remaining HC body, a phenomenon not previously reported in mammals. In contrast, cisplatin treatment results in accumulation of dead HCs in the sensory epithelium, accompanied by an increase in SC death. The surviving SCs constrict fewer HCs and display impaired phagocytosis. These data are supported by in vivo experiments, in which cochlear SCs show reduced capacity for scar formation in cisplatin-treated mice compared with those treated with aminoglycosides. Together, these data point to a broader defect in the ability of the cisplatin-treated SCs, to preserve tissue health in the mature mammalian inner ear. PMID:25929858

  8. Dissecting the bulge in hair regeneration

    OpenAIRE

    Ito, Mayumi; Myung, Peggy

    2012-01-01

    The adult hair follicle houses stem cells that govern the cyclical growth and differentiation of multiple cell types that collectively produce a pigmented hair. Recent studies have revealed that hair follicle stem cells are heterogeneous and dynamic throughout the hair cycle. Moreover, interactions between heterologous stem cells, including both epithelial and melanocyte stem cells, within the hair follicle are just now being explored. This review will describe how recent findings have expand...

  9. Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells.

    Directory of Open Access Journals (Sweden)

    Kumar N Alagramam

    Full Text Available Immunocytochemical studies have shown that protocadherin-15 (PCDH15 and cadherin-23 (CDH23 are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15(av3J (av3J, Pcdh15(av6J (av6J and Cdh23(v2J (v2J mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [(3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [(3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction.

  10. In vitro differentiation of mouse embryonic stem cells into inner ear hair cell-like cells using stromal cell conditioned medium

    OpenAIRE

    Ouji, Y; Ishizaka, S.; NAKAMURA-UCHIYAMA, F; Yoshikawa, M

    2012-01-01

    Hearing loss is mainly caused by loss of sensory hair cells (HCs) in the organ of Corti or cochlea. Although embryonic stem (ES) cells are a promising source for cell therapy, little is known about the efficient generation of HC-like cells from ES cells. In the present study, we developed a single-medium culture method for growing embryoid bodies (EBs), in which conditioned medium (CM) from cultures of ST2 stromal cells (ST2-CM) was used for 14-day cultures of 4-day EBs. At the end of the 14-...

  11. TR3 is preferentially expressed by bulge epithelial stem cells in human hair follicles

    Science.gov (United States)

    Xie, Lin; Yang, Ruifeng; Liu, Shujing; Lyle, Stephen; Cotsarelis, George; Xiang, Leihong; Zhang, Litao; Li, Bin; Wan, Miaojian; Xu, Xiaowei

    2016-01-01

    TR3 is an orphan member of the steroid/thyroid/retinoid nuclear receptor superfamily of transcription factors and it plays a pivotal role in regulating cell growth and apoptosis. The expression and function of TR3 in skin have not been well investigated. Using a cDNA expression assay, we discover that TR3 is significantly enriched in human telogen bulge compared with anagen bulb. Immunohistochemical staining confirms that TR3 is highly expressed in the bulge region of human hair follicles and it colocalizes with cytokeratin 15 (K15), an epithelial stem cell marker. To study the function of TR3 in the effect of androgens in keratinocytes, we treat HaCaT keratinocytes and primary human keratinocytes with dihydrotestosterone (DHT) and testosterone (T). The treated keratinocytes show a dose-dependent growth reduction to DHT and T. DHT increases the expression of TR3 in keratinocytes, associated with a concomitant increase of BAD and decrease of Bcl-2 expression. Knockdown TR3 expression by siRNA blocks the inhibitory effect of DHT on keratinocyte proliferation. Our results demonstrate that TR3 is localized to the stem cell compartment in the human hair follicles. Androgen increases TR3 expression in cultured keratinocytes. Our data suggest that TR3 mediates at least part of the inhibitory effect of androgens on keratinocytes. PMID:26707825

  12. A unique cellular scaling rule in the avian auditory system.

    Science.gov (United States)

    Corfield, Jeremy R; Long, Brendan; Krilow, Justin M; Wylie, Douglas R; Iwaniuk, Andrew N

    2016-06-01

    Although it is clear that neural structures scale with body size, the mechanisms of this relationship are not well understood. Several recent studies have shown that the relationship between neuron numbers and brain (or brain region) size are not only different across mammalian orders, but also across auditory and visual regions within the same brains. Among birds, similar cellular scaling rules have not been examined in any detail. Here, we examine the scaling of auditory structures in birds and show that the scaling rules that have been established in the mammalian auditory pathway do not necessarily apply to birds. In galliforms, neuronal densities decrease with increasing brain size, suggesting that auditory brainstem structures increase in size faster than neurons are added; smaller brains have relatively more neurons than larger brains. The cellular scaling rules that apply to auditory brainstem structures in galliforms are, therefore, different to that found in primate auditory pathway. It is likely that the factors driving this difference are associated with the anatomical specializations required for sound perception in birds, although there is a decoupling of neuron numbers in brain structures and hair cell numbers in the basilar papilla. This study provides significant insight into the allometric scaling of neural structures in birds and improves our understanding of the rules that govern neural scaling across vertebrates. PMID:26002617

  13. Physiological Measures of Auditory Function

    Science.gov (United States)

    Kollmeier, Birger; Riedel, Helmut; Mauermann, Manfred; Uppenkamp, Stefan

    When acoustic signals enter the ears, they pass several processing stages of various complexities before they will be perceived. The auditory pathway can be separated into structures dealing with sound transmission in air (i.e. the outer ear, ear canal, and the vibration of tympanic membrane), structures dealing with the transformation of sound pressure waves into mechanical vibrations of the inner ear fluids (i.e. the tympanic membrane, ossicular chain, and the oval window), structures carrying mechanical vibrations in the fluid-filled inner ear (i.e. the cochlea with basilar membrane, tectorial membrane, and hair cells), structures that transform mechanical oscillations into a neural code, and finally several stages of neural processing in the brain along the pathway from the brainstem to the cortex.

  14. Future horizons in hair restoration.

    Science.gov (United States)

    Marshall, Bryan T; Ingraham, Chris A; Wu, Xunwei; Washenik, Ken

    2013-08-01

    This article reviews the history of hair follicle regeneration from follicular fragments and dissociated cells. The challenges of trichogenic in vitro culture and subsequent delivery into the patient are discussed, as well as cosmetic acceptance, recent achievements on regeneration of human hair follicles, and new potential cell sources for hair regeneration. PMID:24017993

  15. Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.

    Directory of Open Access Journals (Sweden)

    Soung-Hoon Lee

    Full Text Available BACKGROUND: Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA, a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo. METHODOLOGY/ PRINCIPAL FINDINGS: Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP. VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX, a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl(2 also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice. CONCLUSIONS/ SIGNIFICANCE: Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth.

  16. Hair Dye and Hair Relaxers

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Women Hair Dye and Hair Relaxers Share Tweet Linkedin Pin it More sharing ... products. If you have a bad reaction to hair dyes and relaxers, you should: Stop using the product. ...

  17. Engineered deafness reveals that mouse courtship vocalizations do not require auditory experience.

    Science.gov (United States)

    Mahrt, Elena J; Perkel, David J; Tong, Ling; Rubel, Edwin W; Portfors, Christine V

    2013-03-27

    Auditory experience during development is necessary for normal language acquisition in humans. Although songbirds, some cetaceans, and maybe bats may also be vocal learners, vocal learning has yet to be well established for a laboratory mammal. Mice are potentially an excellent model organism for studying mechanisms underlying vocal communication. Mice vocalize in different social contexts, yet whether they learn their vocalizations remains unresolved. To address this question, we compared ultrasonic courtship vocalizations emitted by chronically deaf and normal hearing adult male mice. We deafened CBA/CaJ male mice, engineered to express diphtheria toxin (DT) receptors in hair cells, by systemic injection of DT at postnatal day 2 (P2). By P9, almost all inner hair cells were absent and by P16 all inner and outer hair cells were absent in DTR mice. These mice did not show any auditory brainstem responses as adults. Wild-type littermates, also treated with DT at P2, had normal hair cells and normal auditory brainstem responses. We compared the temporal structure of vocalization bouts, the types of vocalizations, the patterns of syllables, and the acoustic features of each syllable type emitted by hearing and deaf males in the presence of a female. We found that almost all of the vocalization features we examined were similar in hearing and deaf animals. These findings indicate that mice do not need auditory experience during development to produce normal ultrasonic vocalizations in adulthood. We conclude that mouse courtship vocalizations are not acquired through auditory feedback-dependent learning. PMID:23536072

  18. LGR4 and LGR5 Regulate Hair Cell Differentiation in the Sensory Epithelium of the Developing Mouse Cochlea

    Science.gov (United States)

    Żak, Magdalena; van Oort, Thijs; Hendriksen, Ferry G.; Garcia, Marie-Isabelle; Vassart, Gilbert; Grolman, Wilko

    2016-01-01

    In the developing cochlea, Wnt/β-catenin signaling positively regulates the proliferation of precursors and promotes the formation of hair cells by up-regulating Atoh1 expression. Not much, however, is known about the regulation of Wnt/β-catenin activity in the cochlea. In multiple tissues, the activity of Wnt/β-catenin signaling is modulated by an interaction between LGR receptors and their ligands from the R-spondin family. The deficiency in Lgr4 and Lgr5 genes leads to developmental malformations and lethality. Using the Lgr5 knock-in mouse line we show that loss of LGR5 function increases Wnt/β-catenin activity in the embryonic cochlea, resulting in a mild overproduction of inner and outer hair cells (OHC). Supernumerary hair cells are likely formed due to an up-regulation of the “pro-hair cell” transcription factors Atoh1, Nhlh1, and Pou4f3. Using a hypomorphic Lgr4 mouse model we showed a mild overproduction of OHCs in the heterozygous and homozygous Lgr4 mice. The loss of LGR4 function prolonged the proliferation in the mid-basal turn of E13 cochleae, causing an increase in the number of SOX2-positive precursor cells within the pro-sensory domain. The premature differentiation of hair cells progressed in a medial to lateral gradient in Lgr4 deficient embryos. No significant up-regulation of Atoh1 was observed following Lgr4 deletion. Altogether, our findings suggest that LGR4 and LGR5 play an important role in the regulation of hair cell differentiation in the embryonic cochlea.

  19. Descending projections from auditory cortex to excitatory and inhibitory cells in the nucleus of the brachium of the inferior colliculus

    Directory of Open Access Journals (Sweden)

    Jeffrey Garrett Mellott

    2014-10-01

    Full Text Available Descending projections from the auditory cortex (AC terminate in subcortical auditory centers from the medial geniculate nucleus (MG to the cochlear nucleus, allowing the AC to modulate the processing of acoustic information at many levels of the auditory system. The nucleus of the brachium of the inferior colliculus (NBIC is a large midbrain auditory nucleus that is a target of these descending cortical projections. The NBIC is a source of several auditory projections, including an ascending projection to the MG. This ascending projection appears to originate from both excitatory and inhibitory NBIC cells, but whether the cortical projections contact either of these cell groups is unknown. In this study, we first combined retrograde tracing and immunochemistry for glutamic acid decarboxylase (GAD, a marker of GABAergic cells to identify GABAergic and non-GABAergic NBIC projections to the MG. Our first result is that GAD-immunopositive cells constitute ~17% of the NBIC to MG projection. We then used anterograde labeling and electron microscopy to examine the AC projection to the NBIC. Our second result is that cortical boutons in the NBIC form synapses with round vesicles and asymmetric synapses, consistent with excitatory effects. Finally, we combined fluorescent anterograde labeling of corticofugal axons with immunochemistry and retrograde labeling of NBIC cells that project to the MG. These final results suggest first that AC axons contact both GAD-negative and GAD-positive NBIC cells and, second, that some of cortically-contacted cells project to the MG. Overall, the results imply that corticofugal projections can modulate both excitatory and inhibitory ascending projections from the NBIC to the auditory thalamus.

  20. Calmodulin-dependent protein kinases mediate calcium-induced slow motility of mammalian outer hair cells.

    Science.gov (United States)

    Puschner, B; Schacht, J

    1997-08-01

    Cochlear outer hair cells in vitro respond to elevation of intracellular calcium with slow shape changes over seconds to minutes ('slow motility'). This process is blocked by general calmodulin antagonists suggesting the participation of calcium/calmodulin-dependent enzymatic reactions. The present study proposes a mechanism for these reactions. Length changes of outer hair cells isolated from the guinea pig cochlea were induced by exposure to the calcium ionophore ionomycin. ATP levels remained unaffected by this treatment ruling out depletion of ATP (by activation of calcium-dependent ATPases) as a cause of the observed shape changes. Involvement of protein kinases was suggested by the inhibition of shape changes by K252a, a broad-spectrum inhibitor of protein kinase activity. Furthermore, the inhibitors ML-7 and ML-9 blocked the shape changes at concentrations compatible with inhibition of myosin light chain kinase (MLCK). KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), also attenuated the length changes. Inhibitors with selectivity for cyclic nucleotide-dependent protein kinases (H-89, staurosporine) were tested to assess potential additional contributions by such enzymes. The dose dependence of their action supported the notion that the most likely mechanism of slow motility involves phosphorylation reactions catalyzed by MLCK or CaMKII or both. PMID:9282907

  1. Expression of EFR3A in the mouse cochlea during degeneration of spiral ganglion following hair cell loss.

    Directory of Open Access Journals (Sweden)

    Chen Nie

    Full Text Available Retrograde degeneration of spiral ganglion cells in the cochlea following hair cell loss is similar to dying back in pathology. The EFR3A gene has recently been discovered to be involved in the pathogenesis of dying back. The relationship of EFR3A and spiral ganglion degeneration, however, was rarely investigated. In this study, we destroyed the hair cells of the mouse cochlea by co-administration of kanamycin and furosemide and then investigated the EFR3A expression during the induced spiral ganglion cell degeneration. Our results revealed that co-administration of kanamycin and furosemide quickly induced hair cell loss in the C57BL/6J mice and then resulted in progressive degeneration of the spiral ganglion beginning at day 5 following drug administration. The number of the spiral ganglion cells began to decrease at day 15. The expression of EFR3A increased remarkably in the spiral ganglion at day 5 and then decreased to near normal level within the next 10 days. Our study suggested that the change of EFR3A expression in the spiral ganglion was coincident with the time of the spiral ganglion degeneration, which implied that high expression of EFR3A may be important to prompt initiation of spiral ganglion degeneration following hair cell loss.

  2. Mutations in Protocadherin 15 and Cadherin 23 Affect Tip Links and Mechanotransduction in Mammalian Sensory Hair Cells

    OpenAIRE

    Alagramam, Kumar N.; Goodyear, Richard J.; Ruishuang Geng; Furness, David N.; Van Aken, Alexander F J; Walter Marcotti; Kros, Corné J.; Richardson, Guy P.

    2011-01-01

    Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15(av3J) (av3J), Pcdh15(av6J) (av6J) and Cdh23(v2J) (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the tr...

  3. Repeated exposure to hair dye induces regulatory T cells in mice

    DEFF Research Database (Denmark)

    Rubin, I M C; Dabelsteen, S; Nielsen, M M;

    2010-01-01

    We have recently shown that commercial p-phenylenediamine (PPD)-containing hair dyes are potent immune activators that lead to severe contact hypersensitivity in an animal model. However, only a minority of people exposed to permanent hair dyes develops symptomatic contact hypersensitivity. This...... suggests that the majority of people exposed to hair dyes does not become sensitized or develop immunological tolerance....

  4. Activation of BK and SK channels by efferent synapses on outer hair cells in high-frequency regions of the rodent cochlea

    NARCIS (Netherlands)

    Rohmann, Kevin N; Wersinger, Eric; Braude, Jeremy P; Pyott, Sonja J; Fuchs, Paul Albert

    2015-01-01

    Cholinergic neurons of the brainstem olivary complex project to and inhibit outer hair cells (OHCs), refining acoustic sensitivity of the mammalian cochlea. In all vertebrate hair cells studied to date, cholinergic inhibition results from the combined action of ionotropic acetylcholine receptors and

  5. The olivocochlear reflex strength and cochlear sensitivity are independently modulated by auditory cortex microstimulation.

    Science.gov (United States)

    Dragicevic, Constantino D; Aedo, Cristian; León, Alex; Bowen, Macarena; Jara, Natalia; Terreros, Gonzalo; Robles, Luis; Delano, Paul H

    2015-04-01

    In mammals, efferent projections to the cochlear receptor are constituted by olivocochlear (OC) fibers that originate in the superior olivary complex. Medial and lateral OC neurons make synapses with outer hair cells and with auditory nerve fibers, respectively. In addition to the OC system, there are also descending projections from the auditory cortex that are directed towards the thalamus, inferior colliculus, cochlear nucleus, and superior olivary complex. Olivocochlear function can be assessed by measuring a brainstem reflex mediated by auditory nerve fibers, cochlear nucleus neurons, and OC fibers. Although it is known that the OC reflex is activated by contralateral acoustic stimulation and produces a suppression of cochlear responses, the influence of cortical descending pathways in the OC reflex is largely unknown. Here, we used auditory cortex electrical microstimulation in chinchillas to study a possible cortical modulation of cochlear and auditory nerve responses to tones in the absence and presence of contralateral noise. We found that cortical microstimulation produces two different peripheral modulations: (i) changes in cochlear sensitivity evidenced by amplitude modulation of cochlear microphonics and auditory nerve compound action potentials and (ii) enhancement or suppression of the OC reflex strength as measured by auditory nerve responses, which depended on the intersubject variability of the OC reflex. Moreover, both corticofugal effects were not correlated, suggesting the presence of two functionally different efferent pathways. These results demonstrate that auditory cortex electrical microstimulation independently modulates the OC reflex strength and cochlear sensitivity. PMID:25663383

  6. Adult hair follicle stem cells do not retain the older DNA strands in vivo during normal tissue homeostasis.

    Science.gov (United States)

    Waghmare, Sanjeev K; Tumbar, Tudorita

    2013-05-01

    Tissue stem cells have been proposed to segregate the chromosomes asymmetrically (in a non-random manner), thereby retaining preferentially the older "immortal" DNA strands bearing the stemness characteristics into one daughter cell, whereas the newly synthesized strands are segregated to the other daughter cell that will commit to differentiation. Moreover, this non-random segregation would protect the stem cell genome from accumulating multiple mutations during repeated DNA replication. This long-standing hypothesis remains an active subject of study due to conflicting results for some systems and lack of consistency among different tissue stem cell populations. In this review, we will focus on work done in the hair follicle, which is one of the best-understood vertebrate tissue stem cell system to date. In cell culture analysis of paired cultured keratinocytes derived from hair follicle, stem cells suggested a non-random segregation of chromosome with respect to the older DNA strand. In vivo, the hair follicle stem cells appear to self-renew and differentiate at different phases of their homeostatic cycle. The fate decisions occur in quiescence when some stem cells migrate out of their niche and commit to differentiation without self-renewal. The stem cells left behind in the niche self-renew symmetrically and randomly segregate the chromosomes at each division, making more stem cells. This model seems to apply to at least a few other vertebrate tissue stem cells in vivo. PMID:23681654

  7. Hair transplantation.

    Science.gov (United States)

    Avram, Marc R

    2012-12-01

    Hair transplantation is a purely dermatologic surgical procedure that dermatologists should be able to perform in appropriate candidates with hair loss. Hair transplantation techniques performed in the 1960s through the 1990s utilized large grafts that created an unfortunate public image of unnatural-appearing transplanted hair. Over the last 15 years, hair transplantation has been performed using follicular units to create consistently natural-looking transplanted hair in both men and women. This article provides an overview of candidate selection and state-of-the-art techniques for performing hair transplantation. PMID:23409484

  8. Hair medullary cell counts following low-dose-rate γ-and high-energy neutron irradiation

    International Nuclear Information System (INIS)

    Young adult Balb/c mice with hair follicles synchronously in the middle of the hair growth cycle received whole-body or partial-body doses of γ-radiation or neutron radiation. The follicles were analysed 3 days after irradiation in dose-response experiments, or at various times after a constant dose in time-course experiments, for changes in the number of cells in the forming medulla of the hair in the region just above the germinal matrix of the growing (anagen) hair follicle. Time-course experiments showed that 3 days after irradiating growing follicles (2 or 4 Gy of γ-rays or 1 or 2 Gy of neutrons), maximum reduction in the hair medullary cell count (HMCC) was observed. Survival curves were obtained for γ-rays over a range of dose-rates (4.0-0.0023 Gy/min) using total doses between 0.5 and 5.0 Gy. A survival curve was also obtained for 62 MeV neutrons at a dose-rate of 0.31 Gy/min and doses of 0.1-2.0 Gy. (author)

  9. Mycophenolate Antagonizes IFN-γ-Induced Catagen-Like Changes via β-Catenin Activation in Human Dermal Papilla Cells and Hair Follicles

    OpenAIRE

    Sunhyo Ryu; Yonghee Lee; Moo Yeol Hyun; Sun Young Choi; Kwan Ho Jeong; Young Min Park; Hoon Kang; Kui Young Park; Armstrong, Cheryl A.; Andrew Johnson; Peter I. Song; Beom Joon Kim

    2014-01-01

    Recently, various immunosuppressant drugs have been shown to induce hair growth in normal hair as well as in alopecia areata and androgenic alopecia; however, the responsible mechanism has not yet been fully elucidated. In this study, we investigate the influence of mycophenolate (MPA), an immunosuppressant, on the proliferation of human dermal papilla cells (hDPCs) and on the growth of human hair follicles following catagen induction with interferon (IFN)-γ. IFN-γ was found to reduce β-caten...

  10. Manipulation of outer root sheath cell survival perturbs the hair-growth cycle.

    OpenAIRE

    Pena, J C; Kelekar, A; Fuchs, E V; Thompson, C B

    1999-01-01

    Transgenic mice that overexpress the anti-apoptotic gene bcl-xL under the control of the keratin 14 promoter have significantly shorter hair than non-transgenic littermates. The deficit in hair length correlated with a decrease in the duration of anagen, the growth phase of the hair cycle. A prolongation in telogen, the resting phase of the hair cycle, was also observed in adult animals. In the developing hair bulb, bcl-xL transgene expression was observed exclusively in the outer root sheath...

  11. Morphogenetic Mechanisms in the Cyclic Regeneration of Hair Follicles and Deer Antlers from Stem Cells

    Directory of Open Access Journals (Sweden)

    Chunyi Li

    2013-01-01

    Full Text Available We have made comparisons between hair follicles (HFs and antler units (AUs—two seemingly unrelated mammalian organs. HFs are tiny and concealed within skin, whereas AUs are gigantic and grown externally for visual display. However, these two organs share some striking similarities. Both consist of permanent and cyclic/temporary components and undergo stem-cell-based organogenesis and cyclic regeneration. Stem cells of both organs reside in the permanent part and the growth centres are located in the temporary part of each respective organ. Organogenesis and regeneration of both organs depend on epithelial-mesenchymal interactions. Establishment of these interactions requires stem cells and reactive/niche cells (dermal papilla cells for HFs and epidermal cells for AUs to be juxtaposed, which is achieved through destruction of the cyclic part to bring the reactive cells into close proximity to the respective stem cell niche. Developments of HFs and AUs are regulated by similar endocrine (particularly testosterone and paracrine (particularly IGF1 factors. Interestingly, these two organs come to interplay during antlerogenesis. In conclusion, we believe that investigators from the fields of both HF and AU biology could greatly benefit from a comprehensive comparison between these two organs.

  12. Modeling high-frequency electromotility of cochlear outer hair cell in microchamber experiment

    Science.gov (United States)

    Liao, Zhijie; Popel, Aleksander S.; Brownell, William E.; Spector, Alexander A.

    2005-04-01

    Cochlear outer hair cells (OHC) are critically important for the amplification and sharp frequency selectivity of the mammalian ear. The microchamber experiment has been an effective tool to analyze the OHC high-frequency performance. In this study, the OHC electrical stimulation in the microchamber is simulated. The model takes into account the inertial and viscous properties of fluids inside and outside the cell as well as the viscoelastic and piezoelectric properties of the cell composite membrane (wall). The closed ends of the cylindrical cell were considered as oscillatory rigid plates. The final solution was obtained in terms of Fourier series, and it was checked against the available results of the microchamber experiment. The conditions of the interaction between the cell and pipette was analyzed, and it was found that the amount of slip along the contact surface has a significant effect on the cell electromotile response. The cell's length changes were computed as a function of frequency, and their dependence on the viscosities of both fluids and the cell wall was analyzed. The distribution of the viscous losses inside the fluids was also estimated. The proposed approach can help in a better understanding of the high-frequency OHC electromotility under experimental and physiological conditions. .

  13. Inhibition of nitrogen-fixing activity of the cyanobiont affects the localization of glutamine synthetase in hair cells of Azolla.

    Science.gov (United States)

    Uheda, Eiji; Maejima, Kazuhiro

    2009-10-15

    In the Azolla-Anabaena association, the host plant Azolla efficiently incorporates and assimilates ammonium ions that are released from the nitrogen-fixing cyanobiont, probably via glutamine synthetase (GS; EC 6.3.1.2) in hair cells, which are specialized cells protruding into the leaf cavity. In order to clarify the regulatory mechanism underlying ammonium assimilation in the Azolla-Anabaena association, Azolla plants were grown under an argon environment (Ar), in which the nitrogen-fixing activity of the cyanobiont was inhibited specifically and completely. The localization of GS in hair cells was determined by immunoelectron microscopy and quantitative analysis of immunogold labeling. Azolla plants grew healthily under Ar when nitrogen sources, such as NO(3)(-) and NH(4)(+), were provided in the growth medium. Both the number of cyanobacterial cells per leaf and the heterocyst frequency of the plants under Ar were similar to those of plants in a nitrogen environment (N(2)). In hair cells of plants grown under Ar, regardless of the type of nitrogen source provided, only weak labeling of GS was observed in the cytoplasm and in chloroplasts. In contrast, in hair cells of plants grown under N(2), abundant labeling of GS was observed in both sites. These findings indicate that specific inhibition of the nitrogen-fixing activity of the cyanobiont affects the localization of GS isoenzymes. Ammonium fixed and released by the cyanobiont could stimulate GS synthesis in hair cells. Simultaneously, the abundant GS, probably GS1, in these cells, could assimilate ammonium rapidly. PMID:19464754

  14. Auditory Processing Disorders

    Science.gov (United States)

    Auditory Processing Disorders Auditory processing disorders (APDs) are referred to by many names: central auditory processing disorders , auditory perceptual disorders , and central auditory disorders . APDs ...

  15. Gene Expression in Hair Follicle Dermal Papilla Cells after Treatment with Stanozolol

    Directory of Open Access Journals (Sweden)

    M. Reiter

    2009-01-01

    Full Text Available Doping with anabolic agents is a topic in sports where strength is crucial, e.g. sprinting, weight lifting and many more. Testosterone and its functional analogs are the drugs of choice taken as pills, creams, tape or injections to increase muscle mass and body performance, and to reduce body fat. Stanozolol (17β-hydroxy-17α-methyl-5α-androst- 2-eno[3,2c]pyrazol is a testosterone analogue with the same anabolic effect like testosterone but its ring structure makes it possible to take it orally. Therefore, stanozolol is one of the most frequently used anabolic steroids. Common verification methods for anabolic drugs exist, identifying the chemicals in tissues, like hair or blood samples. The idea of this feasibility study was to search for specific gene expression regulations induced by stanozolol to identify the possible influence of the synthetically hormone on different metabolic pathways. Finding biomarkers for anabolic drugs could be supportive of the existing methods and an additional proof for illegal drug abuse. In two separate cell cultures, human HFDPC (hair follicle dermal papilla cells from a female and a male donor were treated with stanozolol. In the female cell culture treatment concentrations of 0 nM (control, 1 nM, 10 nM and 100 nM were chosen. Cells were taken 0 h, 6 h, 24 h and 48 h after stimulation and totalRNA was extracted. Learning from the results of the pilot experiment, the male cell culture was treated in 10 nM and 100 nM concentrations and taken after 0 h, 6 h, 24 h and 72 h. Using quantitative real-time RT-PCR expression of characteristics of different target genes were analysed. Totally 13 genes were selected according to their functionality by screening the actual literature and composed to functional groups: factors of apoptosis regulation were Fas Ligand (FasL, its receptor (FasR, Caspase 8 and Bcl-2. Androgen receptor (AR and both estrogen receptors (ERα, ERβ were summarized in the steroid receptor group

  16. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous......To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

  17. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...

  18. Laser hair removal pearls.

    Science.gov (United States)

    Tierney, Emily P; Goldberg, David J

    2008-03-01

    A number of lasers and light devices are now available for the treatment of unwanted hair. The goal of laser hair removal is to damage stem cells in the bulge of the follicle through the targeting of melanin, the endogenous chromophore for laser and light devices utilized to remove hair. The competing chromophores in the skin and hair, oxyhemoglobin and water, have a decreased absorption between 690 nm and 1000 nm, thus making this an ideal range for laser and light sources. Pearls of laser hair removal are presented in this review, focusing on four areas of recent development: 1 treatment of blond, white and gray hair; 2 paradoxical hypertrichosis; 3 laser hair removal in children; and 4 comparison of lasers and IPL. Laser and light-based technologies to remove hair represents one of the most exciting areas where discoveries by dermatologists have led to novel treatment approaches. It is likely that in the next decade, continued advancements in this field will bring us closer to the development of a more permanent and painless form of hair removal. PMID:18330794

  19. Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function

    Science.gov (United States)

    Zhao, Bo; Wu, Zizhen; Müller, Ulrich

    2016-01-01

    Cochlear hair cells convert sound-induced vibration into electrical signals. FAM65B mutations cause hearing loss by an unknown mechanism. Using biochemistry and stochastic optical reconstruction microscopy (STORM), we show here that Fam65b oligomers form a circumferential ring near the basal taper of the mechanically sensitive stereocilia of murine hair cells. Taperin, a second protein near the taper, forms a dense-core-like structure that is disrupted in the absence of Fam65b. Stereocilia of Fam65b-deficient murine hair cells start to develop, but mechanotransduction is affected and stereocilia deteriorate. Yeast-two-hybrid screens identify RhoC as a Fam65b binding partner. RhoC co-localizes with Fam65b in stereocilia and regulates Fam65b oligomerization. Binding to RhoC and oligomerization are critical for Fam65b function. Our findings thus reveal a highly organized compartment near the base of stereocilia that is critical for hair cell function and affected in disease. DOI: http://dx.doi.org/10.7554/eLife.14222.001 PMID:27269051

  20. The role of hair cells, cilia and ciliary motility in otolith formation in the zebrafish otic vesicle.

    Science.gov (United States)

    Stooke-Vaughan, Georgina A; Huang, Peng; Hammond, Katherine L; Schier, Alexander F; Whitfield, Tanya T

    2012-05-01

    Otoliths are biomineralised structures required for the sensation of gravity, linear acceleration and sound in the zebrafish ear. Otolith precursor particles, initially distributed throughout the otic vesicle lumen, become tethered to the tips of hair cell kinocilia (tether cilia) at the otic vesicle poles, forming two otoliths. We have used high-speed video microscopy to investigate the role of cilia and ciliary motility in otolith formation. In wild-type ears, groups of motile cilia are present at the otic vesicle poles, surrounding the immotile tether cilia. A few motile cilia are also found on the medial wall, but most cilia (92-98%) in the otic vesicle are immotile. In mutants with defective cilia (iguana) or ciliary motility (lrrc50), otoliths are frequently ectopic, untethered or fused. Nevertheless, neither cilia nor ciliary motility are absolutely required for otolith tethering: a mutant that lacks cilia completely (MZovl) is still capable of tethering otoliths at the otic vesicle poles. In embryos with attenuated Notch signalling [mindbomb mutant or Su(H) morphant], supernumerary hair cells develop and otolith precursor particles bind to the tips of all kinocilia, or bind directly to the hair cells' apical surface if cilia are absent [MZovl injected with a Su(H)1+2 morpholino]. However, if the first hair cells are missing (atoh1b morphant), otolith formation is severely disrupted and delayed. Our data support a model in which hair cells produce an otolith precursor-binding factor, normally localised to tether cell kinocilia. We also show that embryonic movement plays a minor role in the formation of normal otoliths. PMID:22461562

  1. Radiation induced damage to the cells of pig hairs: a biological indicator of radiation dose and dose distribution in skin

    International Nuclear Information System (INIS)

    Radiation damage to the matrix cells of actively growing pig hairs resulted in a transient reduction in diameter. This was clearly dose dependent for doses in the range 0.5-5 Gy for 250 kV X rays and 3-8 Gy surface dose for 90Sr β rays. While the relationship between the percentage reduction in hair diameter and the X ray dose was linear between 0.5 and 5 Gy, the skin surface dose for β rays and the percentage reduction in hair diameter was found to be best fitted by a quadratic equation. Differences in the effect produced by X and β ray irradiation can be attributed to the absorption of β rays with depth in the dermis and a correction for this has been applied. This system would appear to have considerable potential for use as a biological dosemeter. (author)

  2. Membrane recycling at the infranuclear pole of the outer hair cell

    Science.gov (United States)

    Harasztosi, Csaba; Harasztosi, Emese; Gummer, Anthony W.

    2015-12-01

    Rapid endocytic activity of outer hair cells (OHCs) in the guinea-pig cochlea has been already studied using the fluorescent membrane marker FM1-43. It was demonstrated that vesicles were endocytosed at the apical pole of OHCs and transcytosed to the basolateral membrane and through a central strand towards the nucleus. The significance of endocytic activity in the infranuclear region is still not clear. Therefore, in this study endocytic activity at the synaptic pole of OHCs was investigated. Confocal laser scanning microscopy was used to visualize dye uptake of OHCs isolated from the guinea-pig cochlea. Signal intensity changes were quantified in the apical and basal poles relative to the signal at the membrane. Data showed no significant difference in fluorescent signal intensity changes between the opposite poles of the OHC. These results suggest that endocytic activities in both the basal and the apical poles contribute equally to the membrane recycling of OHCs.

  3. Hair-bundle friction from transduction channels' gating forces

    Science.gov (United States)

    Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

    2015-12-01

    Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. We have shown recently that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle and thus provide a major source of damping [2]. We develop here a physical theory of passive hair-bundle mechanics that explains the origin of channel friction. We show that channel friction can be understood quantitatively by coupling the dynamics of the conformational change associated with channel gating to tip-link tension. As a result, varying channel properties affects friction, with faster channels producing smaller friction. The analysis emphasizes the dual role of transduction channels' gating forces, which affect both hair-bundle stiffness and drag. Friction originating from gating of ion channels is a general concept that is relevant to all mechanosensitive channels.

  4. Expression of nicotinic acetylcholine receptor subunit α9 in type Ⅱ vestibular hair cells of rats

    Institute of Scientific and Technical Information of China (English)

    Wei-jia KONG; Hua-mao CHENG; Paul van CAUWENBERGE

    2006-01-01

    Aim: To explore the cell specific existence of α9 AChR in the vestibular type Ⅱ hair cells (VHC Ⅱ) of rats. Methods: To detect the expression of α9 AChR messenger RNA (mRNA) in the vestibular endorgans and single VHC Ⅱ of rats by using the reverse transcription polymerase chain reaction (RT-PCR) technique and the single cell RT-PCR technique, respectively. Results: It was shown that α9 AChR mRNA was detected in the vestibular endorgans. By using single-cell RT-PCR, mRNA encoding α9 AChR was also detected in the VHC Ⅱ of the rats. Sequence analysis of the PCR products confirmed identity to corresponding cDNA sequence in the predicted region. Conclusion: We established a method which could effectively detect the cell specific expression of mRNA in an individual VHC. Present data confirm that α9 AChR mRNA is expressed in the VHC Ⅱ of rats and indicates that α9 AChR may function as a mediator of efferent cholinergic signaling in mammalian VHC.

  5. Dynamics of Lgr6+ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis

    Directory of Open Access Journals (Sweden)

    Anja Füllgrabe

    2015-11-01

    Full Text Available The dynamics and interactions between stem cell pools in the hair follicle (HF, sebaceous gland (SG, and interfollicular epidermis (IFE of murine skin are still poorly understood. In this study, we used multicolor lineage tracing to mark Lgr6-expressing basal cells in the HF isthmus, SG, and IFE. We show that these Lgr6+ cells constitute long-term self-renewing populations within each compartment in adult skin. Quantitative analysis of clonal dynamics revealed that the Lgr6+ progenitor cells compete neutrally in the IFE, isthmus, and SG, indicating population asymmetry as the underlying mode of tissue renewal. Transcriptional profiling of Lgr6+ and Lgr6− cells did not reveal a distinct Lgr6-associated gene expression signature, raising the question of whether Lgr6 expression requires extrinsic niche signals. Our results elucidate the interrelation and behavior of Lgr6+ populations in the IFE, HF, and SG and suggest population asymmetry as a common mechanism for homeostasis in several epithelial skin compartments.

  6. Is there a relationship between brain-derived neurotrophic factor for driving neuronal auditory circuits with onset of auditory function and the changes following cochlear injury or during aging?

    Science.gov (United States)

    Schimmang, T; Durán Alonso, B; Zimmermann, U; Knipper, M

    2014-12-26

    Brain-derived neurotrophic factor, BDNF, is one of the most important neurotrophic factors acting in the peripheral and central nervous system. In the auditory system its function was initially defined by using constitutive knockout mouse mutants and shown to be essential for survival of neurons and afferent innervation of hair cells in the peripheral auditory system. Further examination of BDNF null mutants also revealed a more complex requirement during re-innervation processes involving the efferent system of the cochlea. Using adult mouse mutants defective in BDNF signaling, it could be shown that a tonotopical gradient of BDNF expression within cochlear neurons is required for maintenance of a specific spatial innervation pattern of outer hair cells and inner hair cells. Additionally, BDNF is required for maintenance of voltage-gated potassium channels (KV) in cochlear neurons, which may form part of a maturation step within the ascending auditory pathway with onset of hearing and might be essential for cortical acuity of sound-processing and experience-dependent plasticity. A presumptive harmful role of BDNF during acoustic trauma and consequences of a loss of cochlear BDNF during aging are discussed in the context of a partial reversion of this maturation step. We compare the potentially beneficial and harmful roles of BDNF for the mature auditory system with those BDNF functions known in other sensory circuits, such as the vestibular, visual, olfactory, or somatosensory system. PMID:25064058

  7. Herbal Extracts Induce Dermal Papilla Cell Proliferation of Human Hair Follicles

    OpenAIRE

    Rastegar, Hosein; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Barikbin, Behrooz; Ehsani, Amirohushang

    2015-01-01

    Background The number of people suffering from balding or hair thinning is increasing, despite the advances in various medical therapies. Therefore, it is highly important to develop new therapies to inhibit balding and increase hair proliferation. Objective We investigated the effects of herbal extracts commonly used for improving balding in traditional medicine to identify potential agents for hair proliferation. Methods The expression levels of 5α-reductase isoforms (type I and II) were an...

  8. Antigen presenting cells in the skin of a patient with hair loss and systemic lupus erythematosus

    OpenAIRE

    Ana Maria Abreu Velez; Julia G Girard; Michael S. Howard,

    2009-01-01

    Context: Hair loss is one of the most striking clinical features of active systemic lupus erythematosus (SLE), however, very few studies have investigated the immunological features of this process. Case report: We describe a 33 years old female who presented with scalp hair loss and arthralgias. Physical examination revealed erythematous plaques on the nose and scalp, with bitemporal hair loss. Scalp biopsies revealed epidermal hyperkeratosis, with a mild interface infiltrate of lymphocytes ...

  9. Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice.

    Directory of Open Access Journals (Sweden)

    Mary Ann Cheatham

    Full Text Available A knockin (KI mouse expressing mutated prestinV499G/Y501H (499 prestin was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI's were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin's motor function in cochlear amplification.

  10. Investigation of hair dye deposition, hair color loss, and hair damage during multiple oxidative dyeing and shampooing cycles.

    Science.gov (United States)

    Zhang, Guojin; McMullen, Roger L; Kulcsar, Lidia

    2016-01-01

    Color fastness is a major concern for consumers and manufacturers of oxidative hair dye products. Hair dye loss results from multiple wash cycles in which the hair dye is dissolved by water and leaches from the hair shaft. In this study, we carried out a series of measurements to help us better understand the kinetics of the leaching process and pathways associated with its escape from the fiber. Hair dye leaching kinetics was measured by suspending hair in a dissolution apparatus and monitoring the dye concentration in solution (leached dye) with an ultraviolet-visible spectrophotometer. The physical state of dye deposited in hair fibers was evaluated by a reflectance light microscopy technique, based on image stacking, allowing enhanced depth of field imaging. The dye distribution within the fiber was monitored by infrared spectroscopic imaging of hair fiber cross sections. Damage to the ultrafine structure of the hair cuticle (surface, endocuticle, and cell membrane complex) and cortex (cell membrane complex) was determined in hair cross sections and on the hair fiber surface with atomic force microscopy. Using differential scanning calorimetry, we investigated how consecutive coloring and leaching processes affect the internal proteins of hair. Further, to probe the surface properties of hair we utilized contact angle measurements. This study was conducted on both pigmented and nonpigmented hair to gain insight into the influence of melanin on the hair dye deposition and leaching processes. Both types of hair were colored utilizing a commercial oxidative hair dye product based on pyrazole chemistry. PMID:27319056

  11. Multifunctional Merkel cells: their roles in electromagnetic reception, finger-print formation, Reiki, epigenetic inheritance and hair form.

    Science.gov (United States)

    Irmak, M Kemal

    2010-08-01

    Merkel cells are located in glabrous and hairy skin and in some mucosa. They are characterized by dense-core secretory granules and cytoskeletal filaments. They are attached to neighboring keratinocytes by desmosomes and contain melanosomes similar to keratinocytes. They are excitable cells in close contact with sensory nerve endings but their function is still unclear. In this review, following roles are attributed for the first time to the Merkel cells: (1) melanosomes in Merkel cells may be involved in mammalian magnetoreception. In this model melanosome as a biological magnetite is connected by cytoskeletal filaments to mechanically gated ion channels embedded in the Merkel cell membrane. The movement of melanosome with the changing electromagnetic field may open ion channels directly producing a receptor potential that can be transmitted to brain via sensory neurons. (2) Merkel cells may be involved in finger-print formation: Merkel cells in glabrous skin are located at the base of the epidermal ridges the type of which defines the finger-print pattern. Finger-print formation starts at the 10th week of pregnancy after the arrival of Merkel cells. Keratinocyte proliferation and the buckling process observed in the basal layer of epidermis resulting in the epidermal ridges may be controlled and formed by Merkel cells. (3) Brain-Merkel cell connection is bi-directional and Merkel cells not only absorb but also radiate the electromagnetic frequencies. Hence, efferent aspects of the palmar and plantar Merkel nerve endings may form the basis of the biofield modalities such as Reiki, therapeutic touch and telekinesis. (4) Adaptive geographic variations such as skin color, craniofacial morphology and hair form result from interactions between environmental factors and epigenetic inheritance system. While environmental factors produce modifications in the body, they simultaneously induce epigenetic modifications in the oocytes and in this way adaptive changes could be

  12. Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche.

    Science.gov (United States)

    Harries, Matthew J; Meyer, Katja; Chaudhry, Iskander; E Kloepper, Jennifer; Poblet, Enrique; Griffiths, Christopher Em; Paus, Ralf

    2013-10-01

    Lichen planopilaris (LPP) is a chronic inflammatory disease of unknown pathogenesis that leads to permanent hair loss. Whilst destruction of epithelial hair follicle stem cells (eHFSCs) that reside in an immunologically protected niche of the HF epithelium, the bulge, is a likely key event in LPP pathogenesis, this remains to be demonstrated. We have tested the hypotheses that bulge immune privilege (IP) collapse and inflammation-induced eHFSC death are key components in the pathogenesis of LPP. Biopsies of lesional and non-lesional scalp skin from adult LPP patients (n = 42) were analysed by quantitative (immuno)histomorphometry, real-time quantitative polymerase chain reaction (qRT-PCR), laser capture microdissection and microarray analysis, or skin organ culture. At both the protein and transcriptional level, lesional LPP HFs showed evidence for bulge IP collapse (ie increased expression of MHC class I and II, β2microglobulin; reduced TGFβ2 and CD200 expression). This was accompanied by a Th1-biased cytotoxic T cell response (ie increased CD8(+) GranzymeB(+) T cells and CD123(+) plasmacytoid dendritic cells, with increased CXCR3 expression) and increased expression of interferon-inducible chemokines (CXCL9/10/11). Interestingly, lesional LPP eHFSCs showed both increased proliferation and apoptosis in situ. Microarray analysis revealed a loss of eHFSC signatures and increased expression of T cell activation/binding markers in active LPP, while bulge PPARγ transcription was unaltered compared to non-lesional LPP HFs. In organ culture of non-lesional LPP skin, interferon-γ (IFNγ) induced bulge IP collapse. LPP is an excellent model disease for studying and preventing immune destruction of human epithelial stem cells in situ. These novel findings raise the possibility that LPP represents an autoimmune disease in whose pathogenesis IFNγ-induced bulge IP collapse plays an important role. Therapeutically, bulge IP protection/restoration may help to better manage

  13. Hair removal

    DEFF Research Database (Denmark)

    Haedersdal, Merete; Haak, Christina S

    2011-01-01

    suitable for targeting follicular and hair shaft melanin: normal mode ruby laser (694 nm), normal mode alexandrite laser (755 nm), pulsed diode lasers (800, 810 nm), long-pulse Nd:YAG laser (1,064 nm), and intense pulsed light (IPL) sources (590-1,200 nm). The ideal patient has thick dark terminal hair......Hair removal with optical devices has become a popular mainstream treatment that today is considered the most efficient method for the reduction of unwanted hair. Photothermal destruction of hair follicles constitutes the fundamental concept of hair removal with red and near-infrared wavelengths......, white skin, and a normal hormonal status. Currently, no method of lifelong permanent hair eradication is available, and it is important that patients have realistic expectations. Substantial evidence has been found for short-term hair removal efficacy of up to 6 months after treatment with the available...

  14. Hair Removal

    DEFF Research Database (Denmark)

    Hædersdal, Merete

    2011-01-01

    suitable for targeting follicular and hair shaft melanin: normal mode ruby laser (694 nm), normal mode alexandrite laser (755 nm), pulsed diode lasers (800, 810 nm), long-pulse Nd:YAG laser (1,064 nm), and intense pulsed light (IPL) sources (590-1,200 nm). The ideal patient has thick dark terminal hair......Hair removal with optical devices has become a popular mainstream treatment that today is considered the most efficient method for the reduction of unwanted hair. Photothermal destruction of hair follicles constitutes the fundamental concept of hair removal with red and near-infrared wavelengths......, white skin, and a normal hormonal status. Currently, no method of lifelong permanent hair eradication is available, and it is important that patients have realistic expectations. Substantial evidence has been found for short-term hair removal efficacy of up to 6 months after treatment with the available...

  15. Hair Removal

    Science.gov (United States)

    ... that's also found in your fingernails and toenails. Hair growth begins beneath the surface of your skin at ... provide cushioning and protection. In some cases, excess hair growth, called hirsutism (pronounced: hur -soo-tih-zum), may ...

  16. Hair Transplants

    Science.gov (United States)

    ... Sweating Facial Redness Frown Lines and Forehead Furrows Hair Loss Sagging Skin Scars Skin Growths Skin Lesions Spider ... Sweating Facial Redness Frown Lines and Forehead Furrows Hair Loss Sagging Skin Scars Skin Growths Skin Lesions Spider ...

  17. Comparison of peripheral compression estimates using auditory steady-state responses (ASSR) and distortion product otoacoustic emissions (DPOAE)

    DEFF Research Database (Denmark)

    Encina Llamas, Gerard; Epp, Bastian; Dau, Torsten

    The healthy auditory system shows a compressive input/output (I/O) function as a result of healthy outer-hair cell function. Hearing impairment often leads to a decrease in sensitivity and a reduction of compression, mainly caused by loss of inner and/or outer hair cells. Compression is commonly...... (DPOAEs) recordings. Results show compressive ASSR I/O functions for NH subjects. For HI subjects, ASSR reveal the loss of sensitivity at low stimulus levels. Growth slopes are smaller (more compressive) in ASSR than in DPOAE I/O functions....

  18. Hair cosmetics

    OpenAIRE

    Nina Madnani; Kaleem Khan

    2013-01-01

    The hair cosmetic industry has undergone a revolutionary change over the last two decades. The focus has dramatically veered from merely cleaning to repair, increasing the tensile strength, reducing oxidative damage, and stimulating growth. Newer shorter procedures to make hair look naturally more lustrous, smooth, and manageable have evolved. Specialized grooming products have been formulated to cleanse, calm, and condition the hair, and are tailored for different hair-types, for example, dr...

  19. In Vivo Cochlear Hair Cell Generation and Survival by Coactivation of β-Catenin and Atoh1

    OpenAIRE

    Kuo, Bryan R.; Baldwin, Emily M.; Layman, Wanda S.; Taketo, Makoto Mark; Zuo, Jian

    2015-01-01

    The mammalian cochlea exhibit minimal spontaneous regeneration, and loss of sensory hair cells (HCs) results in permanent hearing loss. In nonmammalian vertebrates, spontaneous HC regeneration occurs through both proliferation and differentiation of surrounding supporting cells (SCs). HC regeneration in postnatal mammalian cochleae in vivo remains limited by the small HC number and subsequent death of regenerated HCs. Here, we describe in vivo generation of 10-fold more new HCs in the mouse c...

  20. Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling

    OpenAIRE

    Sennett, Rachel; Rendl, Michael

    2012-01-01

    Embryonic hair follicle induction and formation are regulated by mesenchymal-epithelial interactions between specialized dermal cells and epidermal stem cells that switch to a hair fate. Similarly, during postnatal hair growth, communication between mesenchymal dermal papilla cells and surrounding epithelial matrix cells coordinates hair shaft production. Adult hair follicle regeneration in the hair cycle again is thought to be controlled by activating signals originating from the mesenchymal...

  1. Hair cosmetics

    Directory of Open Access Journals (Sweden)

    Nina Madnani

    2013-01-01

    Full Text Available The hair cosmetic industry has undergone a revolutionary change over the last two decades. The focus has dramatically veered from merely cleaning to repair, increasing the tensile strength, reducing oxidative damage, and stimulating growth. Newer shorter procedures to make hair look naturally more lustrous, smooth, and manageable have evolved. Specialized grooming products have been formulated to cleanse, calm, and condition the hair, and are tailored for different hair-types, for example, dry, dry-damaged, oily, colored, and gray hair. Other products are formulated to alter the color or structure of the hair shaft, for example, hair dyes, perming/relaxing. Hair sprays and waxes/gels, can alter the ′lift′ of the hair-shaft. Although dermatologists are experts in managing scalp and hair diseases, the esthetic applications of newer cosmetic therapies still remain elusive. This article attempts to fill the lacunae in our knowledge of hair cosmetics and esthetic procedures relevant in today′s rapidly changing beauty-enhancing industry, with special emphasis on the Indian scenario for chemical and ′natural′ hair products.

  2. Neural Stem Cells Injected into the Sound-Damaged Cochlea Migrate Throughout the Cochlea and Express Markers of Hair Cells, Supporting Cells, and Spiral Ganglion Cells

    Science.gov (United States)

    Corliss, Deborah A.; Gray, Brianna; Anderson, Julia K.; Bobbin, Richard P.; Snyder, Evan Y.; Cotanche, Douglas A.

    2007-01-01

    Most cases of hearing loss are caused by the death or dysfunction of one of the many cochlear cell types. We examined whether cells from a neural stem cell line could replace cochlear cell types lost after exposure to intense noise. For this purpose, we transplanted a clonal stem cell line into the scala tympani of sound damaged mice and guinea pigs. Utilizing morphological, protein expression and genetic criteria, stem cells were found with characteristics of both neural tissues (satellite, spiral ganglion and Schwann cells) and cells of the organ of Corti (hair cells, supporting cells). Additionally, noise-exposed, stem cell-injected animals exhibited a small but significant increase in the number of satellite cells and Type I spiral ganglion neurons compared to non-injected noise-exposed animals. These results indicate that cells of this neural stem cell line migrate from the scala tympani to Rosenthal's canal and the organ of Corti. Moreover, it suggests that cells of this neural stem cell line may derive some information needed from the microenvironment of the cochlea to differentiate into replacement cells in the cochlea. PMID:17659854

  3. Spontaneous activity in the developing auditory system.

    Science.gov (United States)

    Wang, Han Chin; Bergles, Dwight E

    2015-07-01

    Spontaneous electrical activity is a common feature of sensory systems during early development. This sensory-independent neuronal activity has been implicated in promoting their survival and maturation, as well as growth and refinement of their projections to yield circuits that can rapidly extract information about the external world. Periodic bursts of action potentials occur in auditory neurons of mammals before hearing onset. This activity is induced by inner hair cells (IHCs) within the developing cochlea, which establish functional connections with spiral ganglion neurons (SGNs) several weeks before they are capable of detecting external sounds. During this pre-hearing period, IHCs fire periodic bursts of Ca(2+) action potentials that excite SGNs, triggering brief but intense periods of activity that pass through auditory centers of the brain. Although spontaneous activity requires input from IHCs, there is ongoing debate about whether IHCs are intrinsically active and their firing periodically interrupted by external inhibitory input (IHC-inhibition model), or are intrinsically silent and their firing periodically promoted by an external excitatory stimulus (IHC-excitation model). There is accumulating evidence that inner supporting cells in Kölliker's organ spontaneously release ATP during this time, which can induce bursts of Ca(2+) spikes in IHCs that recapitulate many features of auditory neuron activity observed in vivo. Nevertheless, the role of supporting cells in this process remains to be established in vivo. A greater understanding of the molecular mechanisms responsible for generating IHC activity in the developing cochlea will help reveal how these events contribute to the maturation of nascent auditory circuits. PMID:25296716

  4. Cytosolic Ca(2+) Signals Enhance the Vacuolar Ion Conductivity of Bulging Arabidopsis Root Hair Cells.

    Science.gov (United States)

    Wang, Yi; Dindas, Julian; Rienmüller, Florian; Krebs, Melanie; Waadt, Rainer; Schumacher, Karin; Wu, Wei-Hua; Hedrich, Rainer; Roelfsema, M Rob G

    2015-11-01

    Plant cell expansion depends on the uptake of solutes across the plasma membrane and their storage within the vacuole. In contrast to the well-studied plasma membrane, little is known about the regulation of ion transport at the vacuolar membrane. We therefore established an experimental approach to study vacuolar ion transport in intact Arabidopsis root cells, with multi-barreled microelectrodes. The subcellular position of electrodes was detected by imaging current-injected fluorescent dyes. Comparison of measurements with electrodes in the cytosol and vacuole revealed an average vacuolar membrane potential of -31 mV. Voltage clamp recordings of single vacuoles resolved the activity of voltage-independent and slowly deactivating channels. In bulging root hairs that express the Ca(2+) sensor R-GECO1, rapid elevation of the cytosolic Ca(2+) concentration was observed, after impalement with microelectrodes, or injection of the Ca(2+) chelator BAPTA. Elevation of the cytosolic Ca(2+) level stimulated the activity of voltage-independent channels in the vacuolar membrane. Likewise, the vacuolar ion conductance was enhanced during a sudden increase of the cytosolic Ca(2+) level in cells injected with fluorescent Ca(2+) indicator FURA-2. These data thus show that cytosolic Ca(2+) signals can rapidly activate vacuolar ion channels, which may prevent rupture of the vacuolar membrane, when facing mechanical forces. PMID:26232520

  5. Hair Dyes Resorcinol and Lawsone Reduce Production of Melanin in Melanoma Cells by Tyrosinase Activity Inhibition and Decreasing Tyrosinase and Microphthalmia-Associated Transcription Factor (MITF Expression

    Directory of Open Access Journals (Sweden)

    Shu-Mei Lee

    2015-01-01

    Full Text Available Hair coloring products are one of the most important cosmetics for modern people; there are three major types of hair dyes, including the temporary, semi-permanent and permanent hair dyes. The selected hair dyes (such as ammonium persulfate, sodium persulfate, resorcinol and lawsone are the important components for hair coloring products. Therefore, we analyzed the effects of these compounds on melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes resorcinol and lawsone can reduce the production of melanin. The results also confirmed that resorcinol and lawsone inhibit mushroom and cellular tyrosinase activities in vitro. Resorcinol and lawsone can also downregulate the protein levels of tyrosinase and microphthalmia-associated transcription factor (MITF in B16-F10 cells. Thus, we suggest that frequent use of hair dyes may have the risk of reducing natural melanin production in hair follicles. Moreover, resorcinol and lawsone may also be used as hypopigmenting agents to food, agricultural and cosmetic industry in the future.

  6. Hair dyes resorcinol and lawsone reduce production of melanin in melanoma cells by tyrosinase activity inhibition and decreasing tyrosinase and microphthalmia-associated transcription factor (MITF) expression.

    Science.gov (United States)

    Lee, Shu-Mei; Chen, Yi-Shyan; Lin, Chih-Chien; Chen, Kuan-Hung

    2015-01-01

    Hair coloring products are one of the most important cosmetics for modern people; there are three major types of hair dyes, including the temporary, semi-permanent and permanent hair dyes. The selected hair dyes (such as ammonium persulfate, sodium persulfate, resorcinol and lawsone) are the important components for hair coloring products. Therefore, we analyzed the effects of these compounds on melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes resorcinol and lawsone can reduce the production of melanin. The results also confirmed that resorcinol and lawsone inhibit mushroom and cellular tyrosinase activities in vitro. Resorcinol and lawsone can also downregulate the protein levels of tyrosinase and microphthalmia-associated transcription factor (MITF) in B16-F10 cells. Thus, we suggest that frequent use of hair dyes may have the risk of reducing natural melanin production in hair follicles. Moreover, resorcinol and lawsone may also be used as hypopigmenting agents to food, agricultural and cosmetic industry in the future. PMID:25584612

  7. Hair Dyes Resorcinol and Lawsone Reduce Production of Melanin in Melanoma Cells by Tyrosinase Activity Inhibition and Decreasing Tyrosinase and Microphthalmia-Associated Transcription Factor (MITF) Expression

    Science.gov (United States)

    Lee, Shu-Mei; Chen, Yi-Shyan; Lin, Chih-Chien; Chen, Kuan-Hung

    2015-01-01

    Hair coloring products are one of the most important cosmetics for modern people; there are three major types of hair dyes, including the temporary, semi-permanent and permanent hair dyes. The selected hair dyes (such as ammonium persulfate, sodium persulfate, resorcinol and lawsone) are the important components for hair coloring products. Therefore, we analyzed the effects of these compounds on melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes resorcinol and lawsone can reduce the production of melanin. The results also confirmed that resorcinol and lawsone inhibit mushroom and cellular tyrosinase activities in vitro. Resorcinol and lawsone can also downregulate the protein levels of tyrosinase and microphthalmia-associated transcription factor (MITF) in B16-F10 cells. Thus, we suggest that frequent use of hair dyes may have the risk of reducing natural melanin production in hair follicles. Moreover, resorcinol and lawsone may also be used as hypopigmenting agents to food, agricultural and cosmetic industry in the future. PMID:25584612

  8. Auditory Display

    DEFF Research Database (Denmark)

    volume. The conference's topics include auditory exploration of data via sonification and audification; real time monitoring of multivariate date; sound in immersive interfaces and teleoperation; perceptual issues in auditory display; sound in generalized computer interfaces; technologies supporting...

  9. Neomycin damage and regeneration of hair cells in both mechanoreceptor and electroreceptor lateral line organs of the larval Siberian sturgeon (Acipenser baerii).

    Science.gov (United States)

    Fan, Chunxin; Zou, Sha; Wang, Jian; Zhang, Bo; Song, Jiakun

    2016-05-01

    The lateral line found in some amphibians and fishes has two distinctive classes of sensory organs: mechanoreceptors (neuromasts) and electroreceptors (ampullary organs). Hair cells in neuromasts can be damaged by aminoglycoside antibiotics and they will regenerate rapidly afterward. Aminoglycoside sensitivity and the capacity for regeneration have not been investigated in ampullary organs. We treated Siberian sturgeon (Acipenser baerii) larvae with neomycin and observed loss and regeneration of sensory hair cells in both organs by labeling with DASPEI and scanning electron microscopy (SEM). The numbers of sensory hair cells in both organs were reduced to the lowest levels at 6 hours posttreatment (hpt). New sensory hair cells began to appear at 12 hpt and were regenerated completely in 7 days. To reveal the possible mechanism for ampullary hair cell regeneration, we analyzed cell proliferation and the expression of neural placodal gene eya1 during regeneration. Both cell proliferation and eya1 expression were concentrated in peripheral mantle cells and both increased to the highest level at 12 hpt, which is consistent with the time course for regeneration of the ampullary hair cells. Furthermore, we used Texas Red-conjugated gentamicin in an uptake assay following pretreatment with a cation channel blocker (amiloride) and found that entry of the antibiotic was suppressed in both organs. Together, our results indicate that ampullary hair cells in Siberian sturgeon larvae can be damaged by neomycin exposure and they can regenerate rapidly. We suggest that the mechanisms for aminoglycoside uptake and hair cell regeneration are conserved for mechanoreceptors and electroreceptors. J. Comp. Neurol. 524:1443-1456, 2016. © 2015 Wiley Periodicals, Inc. PMID:26502298

  10. Discrimination between basal cell carcinoma and hair follicles in skin tissue sections by Raman micro-spectroscopy

    Science.gov (United States)

    Larraona-Puy, M.; Ghita, A.; Zoladek, A.; Perkins, W.; Varma, S.; Leach, I. H.; Koloydenko, A. A.; Williams, H.; Notingher, I.

    2011-05-01

    Skin cancer is the most common human malignancy and basal cell carcinoma (BCC) represents approximately 80% of the non-melanoma cases. Current methods of treatment require histopathological evaluation of the tissues by qualified personnel. However, this method is subjective and in some cases BCC can be confused with other structures in healthy skin, including hair follicles. In this preliminary study, we investigated the potential of Raman micro-spectroscopy (RMS) to discriminate between hair follicles and BCC in skin tissue sections excised during Mohs micrographic surgery (MMS). Imaging and diagnosis of skin sections was automatically generated using ' a priori'-built spectral model based on LDA. This model had 90 ± 9% sensitivity and 85 ± 9% specificity for discrimination of BCC from dermis and epidermis. The model used selected Raman bands corresponding to the largest spectral differences between the Raman spectra of BCC and the normal skin regions, associated mainly with nucleic acids and collagen type I. Raman spectra corresponding to the epidermis regions of the hair follicles were found to be closer to those of healthy epidermis rather than BCC. Comparison between Raman spectral images and the gold standard haematoxylin and eosin (H&E) histopathology diagnosis showed good agreement. Some hair follicle regions were misclassified as BCC; regions corresponded mainly to the outermost layer of hair follicle (basal cells) which are expected to have higher nucleic acid concentration. This preliminary study shows the ability of RMS to distinguish between BCC and other tissue structures associated to healthy skin which can be confused with BCC due to their similar morphology.

  11. Fabricating neuromast-inspired gel structures for membrane-based hair cell sensing

    Science.gov (United States)

    Tamaddoni, Nima J.; Stephens, Christopher P.; Sarles, S. A.

    2012-04-01

    Recent research has shown that a new class of mechanical sensor, assembled from biomolecules and which features an artificial cell membrane as the sensing element, can be used to mimic basic hair cell mechanotransduction in vertebrates. The work presented in this paper is motivated by the need to increase sensor performance and stability by refining the methods used to fabricate and connect lipid-encapsulated hydrogels. Inspired by superficial neuromasts found on fish, three hydrogel materials are compared for their ability to be readily shaped into neuromast-inspired geometries and enable lipid bilayer formation using self-assembly at an oil/water interface. Agarose, polyethylene glycol (PEG, 6kg/mole), and hydroxyethyl methacrylate (HEMA) gel materials are compared. The results of this initial study determined that UV-curable gel materials such as PEG and HEMA enable more accurate shaping of the gel-needed for developing a sensor that uses a gel material both for mechanical support and membrane formation-compared to agarose. However, the lower hydrophobicity of agarose and PEG materials provide a more fluid, water-like environment for membrane formation-unlike HEMA. In working toward a neuromast-inspired design, a final experiment demonstrates that a bilayer can also be formed directly between two lipid-covered PEG surfaces. These initial results suggest that candidate gel materials with a low hydrophobicity, high fluidity, and a low modulus can be used to provide membrane support.

  12. On Optimality in Auditory Information Processing

    CERN Document Server

    Karlsson, M

    2000-01-01

    We study limits for the detection and estimation of weak sinusoidal signals in the primary part of the mammalian auditory system using a stochastic Fitzhugh-Nagumo (FHN) model and an action-reaction model for synaptic plasticity. Our overall model covers the chain from a hair cell to a point just after the synaptic connection with a cell in the cochlear nucleus. The information processing performance of the system is evaluated using so called phi-divergences from statistics which quantify a dissimilarity between probability measures and are intimately related to a number of fundamental limits in statistics and information theory (IT). We show that there exists a set of parameters that can optimize several important phi-divergences simultaneously and that this set corresponds to a constant quiescent firing rate (QFR) of the spiral ganglion neuron. The optimal value of the QFR is frequency dependent but is essentially independent of the amplitude of the signal (for small amplitudes). Consequently, optimal proce...

  13. Solubility of Structurally Complicated Materials: 3. Hair

    OpenAIRE

    Horvath, Ari L.

    2009-01-01

    Hair is composed of proteins, lipids, water, and small amounts of trace elements. All proteins in animal and human bodies are built from permutations of amino acid molecules in a polypeptide string. The polypeptide chains of protein keratin are organized into filaments in hair cells. Hair is one of the most difficult proteins to digest or solubilize. Among the most common dissolving procedures for hair are acidic, alkaline, and enzymatic hydrolysis. For the analysis of hair, the solid samples...

  14. Resveratrol attenuates CoCl2-induced cochlear hair cell damage through upregulation of Sirtuin1 and NF-κB deacetylation.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available The goals of this study were to investigate the effects of hypoxia on cochlear hair cell damage, and to explore the role of sirtuin1 in hypoxia-induced hair cell damage. Cochlear organotypic cultures from postnatal day 4 rats were used in this study. Hypoxia was induced by treating cochlear explants with CoCl2. Cochlear cultures were treated with CoCl2 alone or in combination with the sirtuin1 activator resveratrol and the sirtuin1 inhibitor sirtinol. Hair cell damage was identified by phalloidin staining and imaged using scanning electron microscopy. RT-PCR and Western blot analyses were used to detect the expression of sirtuin1 and acetylated nuclear factor-κB (NF-κB. Low concentrations of CoCl2 (100-200 μM did not cause an obvious change in the number and morphology of hair cells, whereas higher concentrations of CoCl2 (300-400 μM induced swelling of hair cells, accompanied by cell loss. Increased sirtuin1 expression was induced by CoCl2 at 100 to 200 μM, but not at 400 μM. NF-κB acetylation was significantly increased in explants treated with 400 μM CoCl2. Pretreatment with resveratrol prevented CoCl2-induced hair cell loss and acetylation of NF-κB. The protective effect of resveratrol was significantly reduced by sirtinol. CoCl2 induces hair cell damage in organotypic cochleae cultures. Resveratrol attenuates CoCl2-induced cochlear hair cell damage possibly via activation of sirtuin1, which deacetylates NF-κB.

  15. Hair-Growth-Promoting Effect of Conditioned Medium of High Integrin α6 and Low CD 71 (α6bri/CD71dim Positive Keratinocyte Cells

    Directory of Open Access Journals (Sweden)

    Chong Hyun Won

    2015-02-01

    Full Text Available Keratinocyte stem/progenitor cells (KSCs reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs and outer root sheath (ORS cells were treated with conditioned medium (CM of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor. A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells.

  16. Fast adaptation and Ca2+-sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells

    OpenAIRE

    Stepanyan, Ruben; Frolenkov, Gregory I.

    2009-01-01

    In inner ear hair cells, activation of mechotransduction channels is followed by extremely rapid deactivation that depends on the influx of Ca2+ through these channels. Although the molecular mechanisms of this “fast” adaptation are largely unknown, the predominant models assume Ca2+ sensitivity as an intrinsic property of yet unidentified mechanotransduction channels. Here we examined mechanotransduction in the hair cells of young postnatal shaker 2 mice (Myo15sh2/sh2). These mice have no fu...

  17. VEGF induces proliferation of human hair follicle dermal papilla cells through VEGFR-2-mediated activation of ERK

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor (VEGF) is one of the strongest regulators of physiological and pathological angiogenesis. VEGF receptor 2 (VEGFR-2), the primary receptor for VEGF, is thought to mediate major functional effects of VEGF. Previously, we have localized both VEGF and VEGFR-2 in human hair follicles. In this study, we further defined the expression and roles of VEGFR-2 on human hair follicle dermal papilla (DP) cells. The expression of VEGFR-2 on DP cells was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis separately, and localization of VEGFR-2 was defined by immunofluorescence. The effect of VEGF on DP cells was analyzed by MTT assays and specific inhibitors. Finally, the role of VEGF involved in the signaling pathways was investigated by Western blot. RT-PCR and Western blot analysis demonstrated the expression of VEGFR-2 on DP cells. Immunostaining for VEGFR-2 showed strong signal on cultured human DP cells in vitro. Exogenous VEGF165 stimulated proliferation of DP cells in a dose-dependent manner. Furthermore, this stimulation was blocked by a VEGFR-2 neutralizing antibody (MAB3571) and an ERK inhibitor (PD98059). VEGF165-induced phosphorylation of ERK1/2 was abolished by MAB3571 and PD98059, while the phosphorylation of p38, JNK and AKT were not changed by VEGF165. Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling. -- Highlights: ► We examine the expression of VEGFR-2 on cultured human dermal papilla (DP) cells. ► VEGF165 stimulated proliferation of human DP cells in a dose-dependent manner. ► This stimulation was through VEGFR-2-mediated activation of ERK.

  18. Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin

    OpenAIRE

    Faucher, Karine; Aas-Hansen, Øyvind; Damsgård, Borge; Laukli, Einar; Stenklev, Niels-Christian

    2009-01-01

    This study addresses the ultrastructural and functional damage and subsequent recovery of the inner ear in the Atlantic cod following intrasaccular gentamicin injection. Inner ear damage was assessed using SEM and measurements of AEP following 250-Hz pure-tone stimuli. Data from gentamicin-treated fish were compared with control (no injection) and sham (injection of saline) fish. Control fish had normal response thresholds associated with welldeveloped hair cell bundle...

  19. Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring

    OpenAIRE

    Kaur, Gurvinder; Kumar, Neeraj; Nandakumar, Ramya; Rapthap, Chowphi C.; Sharma, Gaurav; Neolia, Shekhar; Kumra, Heena; Mahalwar, Prateek; Garg, Abhinav; Kumar, Sunil; Kaur, Jasmeet; Hakim, Mrinali; Kumar, Lalit; Mehra, Narinder K.

    2012-01-01

    Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are ...

  20. Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy

    OpenAIRE

    Sharova, Tatyana Y.; Poterlowicz, Krzysztof; Botchkareva, Natalia V.; Kondratiev, Nikita A.; Aziz, Ahmar; Spiegel, Jeffrey H.; Botchkarev, Vladimir A.; Sharov, Andrey A.

    2014-01-01

    Chemotherapy has severe side-effects for normal rapidly proliferating organs, such as hair follicle, and causes massive apoptosis in hair matrix keratinocytes followed by hair loss. To define the molecular signature of hair follicle response to chemotherapy, human scalp hair follicles cultured ex vivo were treated with doxorubicin and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in doxorubicin-treated hair follic...

  1. A computational model of human auditory signal processing and perception

    DEFF Research Database (Denmark)

    Jepsen, Morten Løve; Ewert, Stephan D.; Dau, Torsten

    2008-01-01

    A model of computational auditory signal-processing and perception that accounts for various aspects of simultaneous and nonsimultaneous masking in human listeners is presented. The model is based on the modulation filterbank model described by Dau et al. [J. Acoust. Soc. Am. 102, 2892 (1997......)] but includes major changes at the peripheral and more central stages of processing. The model contains outer- and middle-ear transformations, a nonlinear basilar-membrane processing stage, a hair-cell transduction stage, a squaring expansion, an adaptation stage, a 150-Hz lowpass modulation filter, a bandpass...... modulation filterbank, a constant-variance internal noise, and an optimal detector stage. The model was evaluated in experimental conditions that reflect, to a different degree, effects of compression as well as spectral and temporal resolution in auditory processing. The experiments include intensity...

  2. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

    Science.gov (United States)

    Deng, Zhili; Lei, Xiaohua; Zhang, Xudong; Zhang, Huishan; Liu, Shuang; Chen, Qi; Hu, Huimin; Wang, Xinyue; Ning, Lina; Cao, Yujing; Zhao, Tongbiao; Zhou, Jiaxi; Chen, Ting; Duan, Enkui

    2015-02-01

    Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen), and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1 (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC activation at the telogen-to-anagen transition. By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation, we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs. Through both gain- and loss-of-function studies in vitro, we show that mTORC1 signaling negatively affects BMP signaling, which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin. Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration. PMID:25609845

  3. Supervillin Is a Component of the Hair Cell’s Cuticular Plate and the Head Plates of Organ of Corti Supporting Cells

    Science.gov (United States)

    Pollock, Lana M.; Gupta, Nilay; Chen, Xi; Luna, Elizabeth J.; McDermott, Brian M.

    2016-01-01

    The organ of Corti has evolved a panoply of cells with extraordinary morphological specializations to harness, direct, and transduce mechanical energy into electrical signals. Among the cells with prominent apical specializations are hair cells and nearby supporting cells. At the apical surface of each hair cell is a mechanosensitive hair bundle of filamentous actin (F-actin)-based stereocilia, which insert rootlets into the F-actin meshwork of the underlying cuticular plate, a rigid organelle considered to hold the stereocilia in place. Little is known about the protein composition and development of the cuticular plate or the apicolateral specializations of organ of Corti supporting cells. We show that supervillin, an F-actin cross-linking protein, localizes to cuticular plates in hair cells of the mouse cochlea and vestibule and zebrafish sensory epithelia. Moreover, supervillin localizes near the apicolateral margins within the head plates of Deiters’ cells and outer pillar cells, and proximal to the apicolateral margins of inner phalangeal cells, adjacent to the junctions with neighboring hair cells. Overall, supervillin localization suggests this protein may shape the surface structure of the organ of Corti. PMID:27415442

  4. Cochlear outer hair cell bio-inspired metamaterial with negative effective parameters

    Science.gov (United States)

    Ma, Fuyin; Wu, Jiu Hui; Huang, Meng; Zhang, Siwen

    2016-05-01

    Inspired by periodical outer hair cells (OHCs) and stereocilia clusters of mammalian cochlear, a type of bio-inspired metamaterial with negative effective parameters based on the OHC structure is proposed. With the structural parameters modified and some common engineering materials adopted, the bio-inspired structure design with length scales of millimeter and lightweight is presented, and then, a bending wave bandgap in a favorable low-frequency with width of 55 Hz during the interval 21-76 or 116 Hz during the interval 57-173 Hz is obtained, i.e., the excellent low-frequency acoustic performance turns up. Compared with the local resonance unit in previous literatures, both the size and weight are greatly reduced in our bio-inspired structure. In addition, the lower edge of low-frequency bandgap is reduced by an order of magnitude, almost to the lower limit frequency of the hearing threshold as well, which achieves an important breakthrough on the aspect of low-frequency and great significance on the noise and vibration reduction in low-frequency range.

  5. Deletion of Tricellulin Causes Progressive Hearing Loss Associated with Degeneration of Cochlear Hair Cells.

    Science.gov (United States)

    Kamitani, Toru; Sakaguchi, Hirofumi; Tamura, Atsushi; Miyashita, Takenori; Yamazaki, Yuji; Tokumasu, Reitaro; Inamoto, Ryuhei; Matsubara, Ai; Mori, Nozomu; Hisa, Yasuo; Tsukita, Sachiko

    2015-01-01

    Tricellulin (also known as MARVELD2) is considered as a central component of tricellular tight junctions and is distributed among various epithelial tissues. Although mutations in the gene encoding tricellulin are known to cause deafness in humans (DFNB49) and mice, the influence of its systemic deletion in vivo remains unknown. When we generated tricellulin-knockout mice (Tric(-/-)), we found an early-onset rapidly progressive hearing loss associated with the degeneration of hair cells (HCs); however, their body size and overall appearance were normal. Tric(-/-) mice did not show any morphological change pertaining to other organs such as the gastrointestinal tract, liver, kidney, thyroid gland and heart. The endocochlear potential (EP) was normal in Tric(-/-) mice, suggesting that the tight junction barrier is maintained in the stria vascularis, where EP is generated. The degeneration of HCs, which occurred after the maturation of EP, was prevented in the culture medium with an ion concentration similar to that of the perilymph. These data demonstrate the specific requirement of tricellulin for maintaining ion homeostasis around cochlear HCs to ensure their survival. The Tric(-/-) mouse provides a new model for understanding the distinct roles of tricellulin in different epithelial systems as well as in the pathogenesis of DFNB49. PMID:26677943

  6. Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bordon, Victoria; Gennery, Andrew R; Slatter, Mary A; Vandecruys, Els; Laureys, Genevieve; Veys, Paul; Qasim, Waseem; Waseem, Qasim; Friedrich, Wilhelm; Wulfraat, Nico M; Scherer, Franziska; Cant, Andrew J; Fischer, Alain; Cavazzana-Calvo, Marina; Cavazanna-Calvo, Marina; Bredius, Robbert G M; Notarangelo, Luigi D; Mazzolari, Evelina; Neven, Benedicte; Güngör, Tayfun; Tayfun, Güngör

    2010-07-01

    Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients. PMID:20375313

  7. Actuation of flexoelectric membranes in viscoelastic fluids with applications to outer hair cells.

    Science.gov (United States)

    Herrera-Valencia, E E; Rey, Alejandro D

    2014-11-28

    Liquid crystal flexoelectric actuation uses an imposed electric field to create membrane bending, and it is used by the outer hair cells (OHCs) located in the inner ear, whose role is to amplify sound through generation of mechanical power. Oscillations in the OHC membranes create periodic viscoelastic flows in the contacting fluid media. A key objective of this work on flexoelectric actuation relevant to OHCs is to find the relations and impact of the electromechanical properties of the membrane, the rheological properties of the viscoelastic media, and the frequency response of the generated mechanical power output. The model developed and used in this work is based on the integration of: (i) the flexoelectric membrane shape equation applied to a circular membrane attached to the inner surface of a circular capillary and (ii) the coupled capillary flow of contacting viscoelastic phases, such that the membrane flexoelectric oscillations drive periodic viscoelastic capillary flows, as in OHCs. By applying the Fourier transform formalism to the governing equation, analytical expressions for the transfer function associated with the curvature and electrical field and for the power dissipation of elastic storage energy were found. PMID:25332388

  8. Hair casts

    Directory of Open Access Journals (Sweden)

    Sweta S Parmar

    2014-01-01

    Full Text Available Hair casts or pseudonits are circumferential concretions,which cover the hair shaft in such a way that, it could be easily removed. They are thin, cylindrical, and elongated in length. We present an unusual case of an 8-year-old girl presenting with hair casts. Occurrence of these is unusual, and they may have varied associations. This patient was suffering from developmental delay. It is commonly misdiagnosed as and very important to differentiate from pediculosis capitis.

  9. Auditory agnosia.

    Science.gov (United States)

    Slevc, L Robert; Shell, Alison R

    2015-01-01

    Auditory agnosia refers to impairments in sound perception and identification despite intact hearing, cognitive functioning, and language abilities (reading, writing, and speaking). Auditory agnosia can be general, affecting all types of sound perception, or can be (relatively) specific to a particular domain. Verbal auditory agnosia (also known as (pure) word deafness) refers to deficits specific to speech processing, environmental sound agnosia refers to difficulties confined to non-speech environmental sounds, and amusia refers to deficits confined to music. These deficits can be apperceptive, affecting basic perceptual processes, or associative, affecting the relation of a perceived auditory object to its meaning. This chapter discusses what is known about the behavioral symptoms and lesion correlates of these different types of auditory agnosia (focusing especially on verbal auditory agnosia), evidence for the role of a rapid temporal processing deficit in some aspects of auditory agnosia, and the few attempts to treat the perceptual deficits associated with auditory agnosia. A clear picture of auditory agnosia has been slow to emerge, hampered by the considerable heterogeneity in behavioral deficits, associated brain damage, and variable assessments across cases. Despite this lack of clarity, these striking deficits in complex sound processing continue to inform our understanding of auditory perception and cognition. PMID:25726291

  10. Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis of sensory hair cells in the mouse inner ear

    Directory of Open Access Journals (Sweden)

    Neil eSegil

    2015-05-01

    Full Text Available Aminoglycoside antibiotics are the drug of choice for treating many bacterial infections, but their administration results in hearing loss in nearly one fourth of the patients who receive them. Several biochemical pathways have been implicated in aminoglycoside antibiotic ototoxicity; however, little is known about how hair cells respond to aminoglycoside antibiotics at the transcriptome level. Here we have investigated the genome-wide response to the aminoglycoside antibiotic gentamicin. Using organotypic cultures of the perinatal organ of Corti, we performed RNA sequencing using cDNA libraries obtained from FACS-purified hair cells. Within 3 hours of gentamicin treatment, the messenger RNA level of more than three thousand genes in hair cells changed significantly. Bioinformatic analysis of these changes highlighted several known signal transduction pathways, including the JNK pathway and the NF-κB pathway, in addition to genes involved in the stress response, apoptosis, cell cycle control, and DNA damage repair. In contrast, only 698 genes, mainly involved in cell cycle and metabolite biosynthetic processes, were significantly affected in the non-hair cell population. The gene expression profiles of hair cells in response to gentamicin share a considerable similarity with those previously observed in gentamicin-induced nephrotoxicity. Our findings suggest that previously observed early responses to gentamicin in hair cells in specific signaling pathways are reflected in changes in gene expression. Additionally, the observed changes in gene expression of cell cycle regulatory genes indicate a disruption of the postmitotic state, which may suggest an alternative pathway regulating gentamicin-induced hair cell death. This work provides a more comprehensive view of aminoglycoside antibiotic ototoxicity, and thus contribute to identifying potential pathways or therapeutic targets to alleviate this important side effect of aminoglycoside

  11. Cholesteatoma associated with squamous cell carcinoma of the external auditory canal: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Olfa Ben Gamra

    2015-11-01

    Conclusion: SCC of the external auditory canal can mimic cholesteatoma. A precise diagnosis of the disease is important to predict the treatment outcome. Optimal management relies on early surgery and postoperative radiotherapy, thus offering the greatest chance of cure.

  12. Diffusion tensor imaging of the auditory nerve in patients with acquired single-sided deafness

    DEFF Research Database (Denmark)

    Vos, Sjoerd; Haakma, Wieke; Versnel, Huib;

    2015-01-01

    following cochlear hair cell loss, and the amount of degeneration may considerably differ between the two ears, also in patients with bilateral deafness. A measure that reflects the nerve's condition would help to assess the best of both nerves and decide accordingly which ear should be implanted for...... DTI metrics from the deaf-sided with the healthy-sided nerves in patients showed no significant differences. There was a small but significant reduction in fractional anisotropy in both auditory nerves in patients compared with normal-hearing controls. These results are the first evidence of possible...... changes in the microstructure of the bilateral auditory nerves as a result of single-sided deafness. Our results also indicate that it is too early to assess the degenerative status of the auditory nerve of a subject-specific basis....

  13. Voiced-speech representation by an analog silicon model of the auditory periphery.

    Science.gov (United States)

    Liu, W; Andreou, A G; Goldstein, M H

    1992-01-01

    An analog CMOS integration of a model for the auditory periphery is presented. The model consists of middle ear, basilar membrane, and hair cell/synapse modules which are derived from neurophysiological studies. The circuit realization of each module is discussed, and experimental data of each module's response to sinusoidal excitation are given. The nonlinear speech processing capabilities of the system are demonstrated using the voiced syllable |ba|. The multichannel output of the silicon model corresponds to the time-varying instantaneous firing rates of auditory nerve fibers that have different characteristic frequencies. These outputs are similar to the physiologically obtained responses. The actual implementation uses subthreshold CMOS technology and analog continuous-time circuits, resulting in a real-time, micropower device with potential applications as a preprocessor of auditory stimuli. PMID:18276451

  14. State-dependent and cell type-specific temporal processing in auditory thalamocortical circuit

    OpenAIRE

    Shuzo Sakata

    2016-01-01

    Ongoing spontaneous activity in cortical circuits defines cortical states, but it still remains unclear how cortical states shape sensory processing across cortical laminae and what type of response properties emerge in the cortex. Recording neural activity from the auditory cortex (AC) and medial geniculate body (MGB) simultaneously with electrical stimulations of the basal forebrain (BF) in urethane-anesthetized rats, we investigated state-dependent spontaneous and auditory-evoked activitie...

  15. Slimy hairs: Hair sensors made with slime mould

    OpenAIRE

    Adamatzky, Andrew

    2013-01-01

    Slime mould Physarum polycephalum is a large single cell visible by unaided eye. We design a slime mould implementation of a tactile hair, where the slime mould responds to repeated deflection of hair by an immediate high-amplitude spike and a prolonged increase in amplitude and width of its oscillation impulses. We demonstrate that signal-to-noise ratio of the Physarum tactile hair sensor averages near six for the immediate response and two for the prolonged response.

  16. Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla

    Science.gov (United States)

    Fernandez, C.; Lysakowski, A.; Goldberg, J. M.

    1995-01-01

    1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx

  17. From zebrafish to mammal: functional evolution of prestin, the motor protein of cochlear outer hair cells.

    Science.gov (United States)

    Tan, Xiaodong; Pecka, Jason L; Tang, Jie; Okoruwa, Oseremen E; Zhang, Qian; Beisel, Kirk W; He, David Z Z

    2011-01-01

    Prestin is the motor protein of cochlear outer hair cells. It belongs to a distinct anion transporter family called solute carrier protein 26A, or SLC26A. Members of this family serve two fundamentally distinct functions. Although most members transport different anion substrates across a variety of epithelia, prestin (SLC26A5) is unique, functioning as a voltage-dependent motor protein. Recent evidence suggests that prestin orthologs from zebrafish and chicken are electrogenic divalent/chloride anion exchangers/transporters with no motor function. These studies appear to suggest that prestin was evolved from an anion transporter. We examined the motor and transport functions of prestin and its orthologs from four different species in the vertebrate lineage, to gain insights of how these two physiological functions became distinct. Somatic motility, voltage-dependent nonlinear capacitance (NLC), and transporter function were measured in transfected human embryonic kidney (HEK) cells using voltage-clamp and anion uptake techniques. Zebrafish and chicken prestins both exhibited weak NLC, with peaks significantly shifted in the depolarization (right) direction. This was contrasted by robust NLC with peaks left shifted in the platypus and gerbil. The platypus and gerbil prestins retained little transporter function compared with robust anion transport capacities in the zebrafish and chicken orthologs. Somatic motility was detected only in the platypus and gerbil prestins. There appears to be an inverse relationship between NLC and anion transport functions, whereas motor function appears to have emerged only in mammalian prestin. Our results suggest that motor function is an innovation of therian prestin and is concurrent with diminished transporter capabilities. PMID:21047933

  18. The chloride intracellular channel protein CLIC5 is expressed at high levels in hair cell stereocilia and is essential for normal inner ear function.

    Science.gov (United States)

    Gagnon, Leona H; Longo-Guess, Chantal M; Berryman, Mark; Shin, Jung-Bum; Saylor, Katherine W; Yu, Heping; Gillespie, Peter G; Johnson, Kenneth R

    2006-10-01

    Although CLIC5 is a member of the chloride intracellular channel protein family, its association with actin-based cytoskeletal structures suggests that it may play an important role in their assembly or maintenance. Mice homozygous for a new spontaneous recessive mutation of the Clic5 gene, named jitterbug (jbg), exhibit impaired hearing and vestibular dysfunction. The jbg mutation is a 97 bp intragenic deletion that causes skipping of exon 5, which creates a translational frame shift and premature stop codon. Western blot and immunohistochemistry results confirmed the predicted absence of CLIC5 protein in tissues of jbg/jbg mutant mice. Histological analysis of mutant inner ears revealed dysmorphic stereocilia and progressive hair cell degeneration. In wild-type mice, CLIC5-specific immunofluorescence was detected in stereocilia of both cochlear and vestibular hair cells and also along the apical surface of Kolliker's organ during cochlear development. Refined immunolocalization in rat and chicken vestibular hair cells showed that CLIC5 is limited to the basal region of the hair bundle, similar to the known location of radixin. Radixin immunostaining appeared reduced in hair bundles of jbg mutant mice. By mass spectrometry and immunoblotting, CLIC5 was shown to be expressed at high levels in stereocilia of the chicken utricle, in an approximate 1:1 molar ratio with radixin. These results suggest that CLIC5 associates with radixin in hair cell stereocilia and may help form or stabilize connections between the plasma membrane and the filamentous actin core. PMID:17021174

  19. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S.; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A.; Kernan, Maurice J.; Eberl, Daniel F.; Göpfert, Martin C.

    2015-01-01

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly’s ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility. PMID:26608786

  20. Hearing aid fitting results in a case of a patient with auditory neuropathy

    Directory of Open Access Journals (Sweden)

    Dell´Aringa, Ana Helena Bannwart

    2009-03-01

    Full Text Available Introduction: The Auditory Neuropathy is described recently as a hearing loss characterized by the preservation of outer hair cells and absence of auditory brainstem responses. Objective: To present a case report of hearing aid fitting in a patient with Auditory Neuropathy. Case Report: S.A.P., male, 32 years old, sought the Otorhinolaryngology Service after five years of Guillain-Barré syndrome, complaining of progressive and bilateral tinnitus auditory loss in both ears. The audiological evaluation resulted in: severe sensorioneural hearing deficiency with bilateral irregular configuration; speech recognition rate of 0% and speech detection rate in 35dB in both ears; type A tympanometric curve and absent ipsilateral, bilateral and contralateral reflexes; absence of waves and presence of cochlear microphonics in both ears in the auditory evoked potential and present bilateral distortion product-evoked otoacoustic emissions. The speech perception test was performed with polysyllabic words and lip reading, and presented 44% of hit with hearing aid and 12% without it. Final Comments: Despite the differences in the process of hearing aid habilitation and rehabilitation, we conclude that sound amplification brought benefits to the patient with auditory neuropathy.

  1. BONE MARROW MESENCHYMAL STEM CELLS ARE PROGENITORS IN VITRO FOR INNER EAR HAIR CELLS

    OpenAIRE

    Jeon, Sang-Jun; Oshima, Kazuo; Heller, Stefan; Edge, Albert S. B.

    2006-01-01

    Stem cells have been demonstrated in the inner ear but they do not spontaneously divide to replace damaged sensory cells. Mesenchymal stem cells (MSC) from bone marrow have been reported to differentiate into multiple lineages including neurons, and we therefore asked whether MSCs could generate sensory cells. Overexpression of the prosensory transcription factor, Math1, in sensory epithelial precursor cells induced expression of myosin VIIa, espin, Brn3c, p27Kip, and jagged2, indicating diff...

  2. Normal and aging hair biology and structure 'aging and hair'.

    Science.gov (United States)

    Goodier, Molly; Hordinsky, Maria

    2015-01-01

    Much like an individual's hairstyle, hair fibers along the scalp see a number of changes over the course of one's lifetime. As the decades pass, the shine and volume synonymous with youthful hair may give way to thin, dull, and brittle hair commonly associated with aging. These changes are a result of a compilation of genetic and environmental elements influencing the cells of the hair follicle, specifically the hair follicle stem cells and melanocytes. Telomere shortening, decrease in cell numbers, and particular transcription factors have all been implicated in this process. In turn, these molecular alterations lead to structural modifications of the hair fiber, decrease in melanin production, and lengthening of the telogen phase of the hair cycle. Despite this inevitable progression with aging, there exists an array of treatments such as light therapy, minoxidil, and finasteride which have been designed to mitigate the effects of aging, particularly balding and thinning hair. Although each works through a different mechanism, all aim to maintain or potentially restore the youthful quality of hair. PMID:26370639

  3. CLIC5 Stabilizes Membrane-Actin Filament Linkages at the Base of Hair Cell Stereocilia in a Molecular Complex with Radixin, Taperin, and Myosin VI

    OpenAIRE

    Salles, Felipe T.; Andrade, Leonardo R.; Tanda, Soichi; Grati, M’hamed; Plona, Kathleen L.; Gagnon, Leona H.; Johnson, Kenneth R.; Kachar, Bechara; Berryman, Mark A.

    2013-01-01

    Chloride intracellular channel 5 protein (CLIC5) was originally isolated from microvilli in complex with actin binding proteins including ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeletal linkers. CLIC5 concentrates at the base of hair cell stereocilia and is required for normal hearing and balance in mice, but its functional significance is poorly understood. This study investigated the role of CLIC5 in postnatal development and maintenance of hair bundles. Co...

  4. Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig.

    Science.gov (United States)

    Gillespie, Lisa N; Zanin, Mark P; Shepherd, Robert K

    2015-01-28

    The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the primary auditory neurons (ANs) of the cochlea. However, ANs degenerate in deafness; the preservation of a robust AN target population, in combination with advances in cochlear implant technology, may provide improved hearing outcomes for cochlear implant patients. The exogenous delivery of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 is well known to support AN survival in deafness, and cell-based therapies provide a potential clinically viable option for delivering neurotrophins into the deaf cochlea. This study utilized cells that were genetically modified to express BDNF and encapsulated in alginate microspheres, and investigated AN survival in the deaf guinea pig following (a) cell-based neurotrophin treatment in conjunction with chronic electrical stimulation from a cochlear implant, and (b) long-term cell-based neurotrophin delivery. In comparison to deafened controls, there was significantly greater AN survival following the cell-based neurotrophin treatment, and there were ongoing survival effects for at least six months. In addition, functional benefits were observed following cell-based neurotrophin treatment and chronic electrical stimulation, with a statistically significant decrease in electrically evoked auditory brainstem response thresholds observed during the experimental period. This study demonstrates that cell-based therapies, in conjunction with a cochlear implant, shows potential as a clinically transferable means of providing neurotrophin treatment to support AN survival in deafness. This technology also has the potential to deliver other therapeutic agents, and to be used in conjunction with other biomedical devices for the treatment of a variety of neurodegenerative conditions. PMID:25481440

  5. miR-128 regulates differentiation of hair follicle mesenchymal stem cells into smooth muscle cells by targeting SMAD2.

    Science.gov (United States)

    Wang, Zhihao; Pang, Li; Zhao, Huiying; Song, Lei; Wang, Yuehui; Sun, Qi; Guo, Chunjie; Wang, Bin; Qin, Xiujiao; Pan, Aiqun

    2016-05-01

    Human hair follicle mesenchymal stem cells (hHFMSCs) are an important source of cardiovascular tissue engineering for their differentiation potential into smooth muscle cells (SMCs), yet the molecular pathways underlying such fate determination is unclear. MicroRNAs (miRNAs) are non-coding RNAs that play critical roles in cell differentiation. In present study, we found that miR-128 was remarkably decreased during the differentiation of hHFMSCs into SMCs induced by transforming growth factor-β1 (TGF-β1). Moreover, overexpression of miR-128 led to decreased expression of SMC cellular marker proteins, such as smooth muscle actin (SMA) and calponin, in TGF-β1-induced SMC differentiation. Further, we identified that miR-128 targeted the 3'-UTR of SMAD2 transcript for translational inhibition of SMAD2 protein, and knockdown of SMAD2 abrogated the promotional effect of antagomir-128 (miR-128 neutralizer) on SMC differentiation. These results suggest that miR-128 regulates the differentiation of hHFMSCs into SMCs via targeting SMAD2, a main transcription regulator in TGF-β signaling pathway involving SMC differentiation. The miR-128/SMAD2 axis could therefore be considered as a candidate target in tissue engineering and regenerative medicine for SMCs. PMID:27087048

  6. Hair Loss

    Science.gov (United States)

    ... 2 • 3 • 4 For Teens For Kids For Parents MORE ON THIS TOPIC Trichotillomania Dealing With a Health Condition Taking Care of Your Hair Skin, Hair, and Nails Body Image and Self-Esteem Alopecia: Kayla's Story Dealing With Cancer Contact Us ...

  7. The Tortoise and the Hair: Slow-Cycling Cells in the Stem Cell Race

    OpenAIRE

    Fuchs, Elaine

    2009-01-01

    Given the importance of stem cells to adult tissues, it has long been postulated that stem cells divide infrequently to preserve their long-term proliferation potential and to prevent the acquisition of errors during DNA replication. Yet, some stem cells must be able to continually churn out progeny in tissues that rapidly turn over or are subject to sudden injuries or growth spurts. This Review explores the challenges that mammalian stem cells face in balancing the competing demands of proli...

  8. Role of creatine in sensitivity and function of the auditory and vestibular system

    Directory of Open Access Journals (Sweden)

    Vahid Moradi

    2015-02-01

    Full Text Available Background and Aim: Creatine plays an important role in the regulation of cellular energy in high energy demand organs such as the inner ear. It is also believed to play a protective role. This article reviewed the mechanisms and effects of creatine on the auditory and vestibular systems.Recent Findings: Creatine transporters and creatine kinase enzymes are involved in converting creatine to creatine phosphate. Phosphate is a fuel cell available in the cochlear and vestibular hair cells and the protective cells, striavascularis, peripheral and central neural pathways to the auditory cortex. It provides essential ATP for auditory and vestibular system performance. Creatine kinase prevents cochlear damage by regulating the metabolism of energy in marginal layers of the striavascularis and preventing free radical production in stressful situations. It also plays an important role in vestibular compensation. Creatine kinase dysfunction leads to an increase in the threshold of auditory brainstem potentials and a reduction in vestibular performance. The use of creatine improves vestibular evoked myogenic potentials and neurologic symptoms.Conclusion: Creatine and creatine kinase protein is essential for normal hearing and balance function and sensitivity. Creatine kinase deficiency impairs the functioning of these two systems; however, creatine consumption may boost the sensitivity of the vestibular system and neurological performance. Effects of the creatine consumption on the auditory system have not yet been examined.

  9. Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea.

    Science.gov (United States)

    Liu, L; Chen, Y; Qi, J; Zhang, Y; He, Y; Ni, W; Li, W; Zhang, S; Sun, S; Taketo, M M; Wang, L; Chai, R; Li, H

    2016-01-01

    Recent studies have reported the role of Wnt/β-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/β-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator β-catenin in HCs, which allowed us to investigate the role of Wnt/β-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of β-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of β-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of β-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while β-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of β-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, β-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that β-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death. PMID:26962686

  10. Analyses of regenerative wave patterns in adult hair follicle populations reveal macro-environmental regulation of stem cell activity

    OpenAIRE

    Plikus, Maksim V; Widelitz, Randall B; Maxson, Rob; Chuong, Cheng-ming

    2009-01-01

    The control of hair growth in the adult mammalian coat is a fascinating topic which has just begun to be explored with molecular genetic tools. Complex hair cycle domains and regenerative hair waves are present in normal adult (> 2 month) mice, but more apparent in mutants with cyclic alopecia phenotypes. Each hair cycle domain consists of initiation site(s), a propagating wave and boundaries. By analyzing the dynamics of hair growth, time required for regeneration after plucking, in situ hyb...

  11. NaHS Protects Cochlear Hair Cells from Gentamicin-Induced Ototoxicity by Inhibiting the Mitochondrial Apoptosis Pathway.

    Directory of Open Access Journals (Sweden)

    Yaodong Dong

    Full Text Available Aminoglycoside antibiotics such as gentamicin could cause ototoxicity in mammalians, by inducing oxidative stress and apoptosis in sensory hair cells of the cochlea. Sodium hydrosulfide (NaHS is reported to alleviate oxidative stress and apoptosis, but its role in protecting aminoglycoside-induced hearing loss is unclear. In this study, we investigated the anti-oxidant and anti-apoptosis effect of NaHS in in vitro cultured House Ear Institute-Organ of Corti 1 (HEI-OC1 cells and isolated mouse cochlea. Results from cultured HEI-OC1 cells and cochlea consistently indicated that NaHS exhibited protective effects from gentamicin-induced ototoxicity, evident by maintained cell viability, hair cell number and cochlear morphology, reduced reactive oxygen species production and mitochondrial depolarization, as well as apoptosis activation of the intrinsic pathway. Moreover, in the isolated cochlear culture, NaHS was also demonstrated to protect the explant from gentamicin-induced mechanotransduction loss. Our study using multiple in vitro models revealed for the first time, the potential of NaHS as a therapeutic agent in protecting against aminoglycoside-induced hearing loss.

  12. Einstein Hair

    CERN Document Server

    Kolyvaris, Theodoros; Papantonopoulos, Eleftherios; Siopsis, George

    2011-01-01

    We consider a gravitating system of vanishing cosmological constant consisting of an electromagnetic field and a scalar field coupled to the Einstein tensor. A Reissner-Nordstr{\\o}m black hole undergoes a second-order phase transition to a hairy black hole of generally anisotropic hair at a certain critical temperature which we compute. The no-hair theorem is evaded due to the coupling between the scalar field and the Einstein tensor ("Einstein hair"). We calculate explicitly the properties of a hairy black hole configuration near the critical temperature and show that it is energetically favorable over the corresponding Reissner-Nordstr{\\o}m black hole.

  13. Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles.

    Science.gov (United States)

    Rezza, Amélie; Wang, Zichen; Sennett, Rachel; Qiao, Wenlian; Wang, Dongmei; Heitman, Nicholas; Mok, Ka Wai; Clavel, Carlos; Yi, Rui; Zandstra, Peter; Ma'ayan, Avi; Rendl, Michael

    2016-03-29

    The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit-amplifying cell (TAC) progenitors that regulates HF morphogenetic growth is largely unknown. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing, we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs, and the DP niche express a plethora of ligands and receptors. Signaling interaction network analysis reveals a bird's-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach, this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth. PMID:27009580

  14. Addition of exogenous NAD+ prevents mefloquine-induced neuroaxonal and hair cell degeneration through reduction of caspase-3-mediated apoptosis in cochlear organotypic cultures.

    Directory of Open Access Journals (Sweden)

    Dalian Ding

    Full Text Available BACKGROUND: Mefloquine is widely used for the treatment of malaria. However, this drug is known to induce neurological side effects including depression, anxiety, balance disorder, and sensorineural hearing loss. Yet, there is currently no treatment for these side effects. PRINCIPAL FINDINGS: In this study, we show that the coenzyme NAD(+, known to play a critical role in maintaining the appropriate cellular redox environment, protects cochlear axons and sensory hair cells from mefloquine-induced degeneration in cultured rat cochleae. Mefloquine alone destroyed hair cells and nerve fiber axons in rat cochlear organotypics cultures in a dose-dependent manner, while treatment with NAD(+ protected axons and hair cells from mefloquine-induced degeneration. Furthermore, cochlear organs treated with mefloquine showed increased oxidative stress marker levels, including superoxide and protein carbonyl, and increased apoptosis marker levels, including TUNEL-positive nuclei and caspases-3. Treatment with NAD(+ reduced the levels of these oxidative stress and apoptosis markers. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings suggest that that mefloquine disrupts the cellular redox environment and induces oxidative stress in cochlear hair cells and nerve fibers leading to caspases-3-mediated apoptosis of these structures. Exogenous NAD(+ suppresses mefloquine-induced oxidative stress and prevents the degeneration of cochlear axons and sensory hair cells caused by mefloquine treatment.

  15. Artificial fish skin of self-powered micro-electromechanical systems hair cells for sensing hydrodynamic flow phenomena.

    Science.gov (United States)

    Asadnia, Mohsen; Kottapalli, Ajay Giri Prakash; Miao, Jianmin; Warkiani, Majid Ebrahimi; Triantafyllou, Michael S

    2015-10-01

    Using biological sensors, aquatic animals like fishes are capable of performing impressive behaviours such as super-manoeuvrability, hydrodynamic flow 'vision' and object localization with a success unmatched by human-engineered technologies. Inspired by the multiple functionalities of the ubiquitous lateral-line sensors of fishes, we developed flexible and surface-mountable arrays of micro-electromechanical systems (MEMS) artificial hair cell flow sensors. This paper reports the development of the MEMS artificial versions of superficial and canal neuromasts and experimental characterization of their unique flow-sensing roles. Our MEMS flow sensors feature a stereolithographically fabricated polymer hair cell mounted on Pb(Zr(0.52)Ti(0.48))O3 micro-diaphragm with floating bottom electrode. Canal-inspired versions are developed by mounting a polymer canal with pores that guide external flows to the hair cells embedded in the canal. Experimental results conducted employing our MEMS artificial superficial neuromasts (SNs) demonstrated a high sensitivity and very low threshold detection limit of 22 mV/(mm s(-1)) and 8.2 µm s(-1), respectively, for an oscillating dipole stimulus vibrating at 35 Hz. Flexible arrays of such superficial sensors were demonstrated to localize an underwater dipole stimulus. Comparative experimental studies revealed a high-pass filtering nature of the canal encapsulated sensors with a cut-off frequency of 10 Hz and a flat frequency response of artificial SNs. Flexible arrays of self-powered, miniaturized, light-weight, low-cost and robust artificial lateral-line systems could enhance the capabilities of underwater vehicles. PMID:26423435

  16. Human Hair: An Educational Tool.

    Science.gov (United States)

    Wells, John

    1983-01-01

    Briefly describes some of the more recent developments in the use of human hairs for such instructional purposes as observing barr bodies and chromosomes, and for culturing to produce cells of both epithelial and fibroblastic morphology. Three main hair categories are also described. (JN)

  17. An in vivo root hair assay for determining rates of apoptotic-like programmed cell death in plants

    Directory of Open Access Journals (Sweden)

    Hogg Bridget V

    2011-12-01

    Full Text Available Abstract In Arabidopsis thaliana we demonstrate that dying root hairs provide an easy and rapid in vivo model for the morphological identification of apoptotic-like programmed cell death (AL-PCD in plants. The model described here is transferable between species, can be used to investigate rates of AL-PCD in response to various treatments and to identify modulation of AL-PCD rates in mutant/transgenic plant lines facilitating rapid screening of mutant populations in order to identify genes involved in AL-PCD regulation.

  18. Hair Loss

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases Cosmetic treatments Dry / sweaty skin Eczema / dermatitis Hair and scalp ...

  19. Your Hair

    Science.gov (United States)

    ... warm and provides a little cushioning for your skull. Eyelashes protect your eyes by decreasing the amount ... Colors What kind of hair do you have — black and curly, blond and straight, or some other ...

  20. Correlation between auditory brainstem recordings and morphology as seen through the scanning electron microscope

    Energy Technology Data Exchange (ETDEWEB)

    Hultcrantz, M.

    1988-09-01

    Pregnant CBA/CBA mice were exposed to 0.5, 1 and 2 Grey (Gy), (1 Gy = 100 rad) in single doses with whole body gamma-irradiation on the 12th, 13th and 16th gestational days, respectively. The animals were tested at an age of one month for vestibular and cochlear function. Thereafter the inner ears were analyzed with scanning electron microscopy. A morphological analysis with cytocochleograms was performed. Morphological changes in the vestibular part showed gross malformations in the cristae ampullares. Hair cells of type I seemed to be more severely changed than hair cells type II. The macula utriculi also showed malformations of the otoconia. All these changes were more pronounced when the irradiation was given early during pregnancy and with the highest doses used, except the otoconia which were more injured when irradiated day 16 of gestation. No disturbances of the equilibrium reflexes were noted. In the cochlea a dose-dependent, time-related damage pattern was demonstrated with pathological changes of outer (OHC) and inner (IHC) hair cells. When tested electrophysiologically for auditory function with auditory brainstem recordings (ABR), elevated thresholds were revealed different in shape depending on when during pregnancy irradiation took place. A good correlation existed between the morphological changes as seen in the cytocochleograms and the functional changes documented with the ABR.

  1. Correlation between auditory brainstem recordings and morphology as seen through the scanning electron microscope

    International Nuclear Information System (INIS)

    Pregnant CBA/CBA mice were exposed to 0.5, 1 and 2 Grey (Gy), (1 Gy = 100 rad) in single doses with whole body gamma-irradiation on the 12th, 13th and 16th gestational days, respectively. The animals were tested at an age of one month for vestibular and cochlear function. Thereafter the inner ears were analyzed with scanning electron microscopy. A morphological analysis with cytocochleograms was performed. Morphological changes in the vestibular part showed gross malformations in the cristae ampullares. Hair cells of type I seemed to be more severely changed than hair cells type II. The macula utriculi also showed malformations of the otoconia. All these changes were more pronounced when the irradiation was given early during pregnancy and with the highest doses used, except the otoconia which were more injured when irradiated day 16 of gestation. No disturbances of the equilibrium reflexes were noted. In the cochlea a dose-dependent, time-related damage pattern was demonstrated with pathological changes of outer (OHC) and inner (IHC) hair cells. When tested electrophysiologically for auditory function with auditory brainstem recordings (ABR), elevated thresholds were revealed different in shape depending on when during pregnancy irradiation took place. A good correlation existed between the morphological changes as seen in the cytocochleograms and the functional changes documented with the ABR

  2. Transplantation of Neural Differentiated Human Mesenchymal Stem Cells into the Cochlea of an Auditory-neuropathy Guinea Pig Model

    OpenAIRE

    Cho, Yong-Bum; Cho, Hyong-Ho; Jang, Sujeong; Jeong, Han-Seong; Park, Jong-Seong

    2011-01-01

    The aim of this study was to determine the effects of transplanted neural differentiated human mesenchymal stem cells (hMSCs) in a guinea pig model of auditory neuropathy. In this study, hMSCs were pretreated with a neural-induction protocol and transplanted into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. A control model was made by injection of Hanks balanced salt solution alone into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. We est...

  3. Effects of ultraviolet-visible irradiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Menon, I.A.; Persad, S.; Ranadive, N.S.; Haberman, H.F.

    1983-07-01

    The present study is an attempt to investigate the possibility that ultraviolet irradiation in the presence of pheomelanin may be more harmful to cells than the irradiation in the presence of eumelanin. The effects of UV-visible irradiation upon Ehrlich ascites carcinoma cells in the presence of the melanin isolated from human black hair (eumelanin) or from red hair (pheomelanin) were investigated. Irradiation of these cells was found to produce cell lysis, as observed by leakage of 51Cr from labeled cells and intracellular lactic dehydrogenase from the cells and decrease in cell viability demonstrated by the trypan blue exclusion test. The three parameters were quantitatively parallel to one another under various experimental conditions, namely different periods of irradiation and irradiation in the presence of different concentrations of melanin. The above effects were more pronounced when the irradiation was carried out in the presence of melanin from red hair than in the presence of black-hair melanin. In the absence of either melanin, the irradiation did not produce any significant effect in cell viability or cell lysis. Irradiation of the cells in the presence of red-hair melanin also decreased the transplantability of these cells. These observations clearly show that irradiation of cells in the presence of pheomelanin could produce cytotoxic effects. The present experimental design may have application in the development of in vitro models for the study of UV radiation-induced cutaneous carcinogenesis. The reactions of pheomelanin may be related to the susceptibility of ''Celtic'' skin to UV radiation-induced skin damage and carcinogenesis.

  4. Effects of ultraviolet-visible irradiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells

    International Nuclear Information System (INIS)

    The present study is an attempt to investigate the possibility that ultraviolet irradiation in the presence of pheomelanin may be more harmful to cells than the irradiation in the presence of eumelanin. The effects of UV-visible irradiation upon Ehrlich ascites carcinoma cells in the presence of the melanin isolated from human black hair (eumelanin) or from red hair (pheomelanin) were investigated. Irradiation of these cells was found to produce cell lysis, as observed by leakage of 51Cr from labeled cells and intracellular lactic dehydrogenase from the cells and decrease in cell viability demonstrated by the trypan blue exclusion test. The three parameters were quantitatively parallel to one another under various experimental conditions, namely different periods of irradiation and irradiation in the presence of different concentrations of melanin. The above effects were more pronounced when the irradiation was carried out in the presence of melanin from red hair than in the presence of black-hair melanin. In the absence of either melanin, the irradiation did not produce any significant effect in cell viability or cell lysis. Irradiation of the cells in the presence of red-hair melanin also decreased the transplantability of these cells. These observations clearly show that irradiation of cells in the presence of pheomelanin could produce cytotoxic effects. The present experimental design may have application in the development of in vitro models for the study of UV radiation-induced cutaneous carcinogenesis. The reactions of pheomelanin may be related to the susceptibility of ''Celtic'' skin to UV radiation-induced skin damage and carcinogenesis

  5. 6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

    Directory of Open Access Journals (Sweden)

    Yong Miao

    Full Text Available Ginger (Zingiber officinale has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.

  6. Auditory Neuropathy

    Science.gov (United States)

    ... field differ in their opinions about the potential benefits of hearing aids, cochlear implants, and other technologies for people with auditory neuropathy. Some professionals report that hearing aids and personal listening devices such as frequency modulation (FM) systems are ...

  7. Myosin-I Isozymes in Neonatal Rodent Auditory and Vestibular Epithelia

    OpenAIRE

    Dumont, Rachel A.; Zhao, Yi-Dong; Holt, Jeffrey R.; Bähler, Martin; Gillespie, Peter G.

    2002-01-01

    Myosin isozymes are essential for hair cells, the sensory cells of the inner ear. Because a myosin-I subfamily member may mediate adaptation of mechanoelectrical transduction, we examined expression of all eight myosin-I isozymes in rodent auditory and vestibular epithelia. Using RT-PCR, we found prominent expression of three isozymes, Myo1b (also known as myosin-Ia or myr 1), Myo1c (myosin-Ib or myr 2), and Myo1e (myr 3). By contrast, Myo1a (brush-border myosin-I), Myo1d (myosin lg or myr 4)...

  8. TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia

    Directory of Open Access Journals (Sweden)

    Kiyoto Kurima

    2015-09-01

    Full Text Available Mechanosensitive ion channels at stereocilia tips mediate mechanoelectrical transduction (MET in inner ear sensory hair cells. Transmembrane channel-like 1 and 2 (TMC1 and TMC2 are essential for MET and are hypothesized to be components of the MET complex, but evidence for their predicted spatiotemporal localization in stereocilia is lacking. Here, we determine the stereocilia localization of the TMC proteins in mice expressing TMC1-mCherry and TMC2-AcGFP. Functionality of the tagged proteins was verified by transgenic rescue of MET currents and hearing in Tmc1Δ/Δ;Tmc2Δ/Δ mice. TMC1-mCherry and TMC2-AcGFP localize along the length of immature stereocilia. However, as hair cells develop, the two proteins localize predominantly to stereocilia tips. Both TMCs are absent from the tips of the tallest stereocilia, where MET activity is not detectable. This distribution was confirmed for the endogenous proteins by immunofluorescence. These data are consistent with TMC1 and TMC2 being components of the stereocilia MET channel complex.

  9. TMC1 and TMC2 Localize at the Site of Mechanotransduction in Mammalian Inner Ear Hair Cell Stereocilia.

    Science.gov (United States)

    Kurima, Kiyoto; Ebrahim, Seham; Pan, Bifeng; Sedlacek, Miloslav; Sengupta, Prabuddha; Millis, Bryan A; Cui, Runjia; Nakanishi, Hiroshi; Fujikawa, Taro; Kawashima, Yoshiyuki; Choi, Byung Yoon; Monahan, Kelly; Holt, Jeffrey R; Griffith, Andrew J; Kachar, Bechara

    2015-09-01

    Mechanosensitive ion channels at stereocilia tips mediate mechanoelectrical transduction (MET) in inner ear sensory hair cells. Transmembrane channel-like 1 and 2 (TMC1 and TMC2) are essential for MET and are hypothesized to be components of the MET complex, but evidence for their predicted spatiotemporal localization in stereocilia is lacking. Here, we determine the stereocilia localization of the TMC proteins in mice expressing TMC1-mCherry and TMC2-AcGFP. Functionality of the tagged proteins was verified by transgenic rescue of MET currents and hearing in Tmc1(Δ/Δ);Tmc2(Δ/Δ) mice. TMC1-mCherry and TMC2-AcGFP localize along the length of immature stereocilia. However, as hair cells develop, the two proteins localize predominantly to stereocilia tips. Both TMCs are absent from the tips of the tallest stereocilia, where MET activity is not detectable. This distribution was confirmed for the endogenous proteins by immunofluorescence. These data are consistent with TMC1 and TMC2 being components of the stereocilia MET channel complex. PMID:26321635

  10. EF-hand protein Ca²⁺ buffers regulate Ca²⁺ influx and exocytosis in sensory hair cells

    OpenAIRE

    Pangršič, Tina; Gabrielaitis, Mantas; Michanski, Susann; Schwaller, Beat; Wolf, Fred; Strenzke, Nicola; Moser, Tobias

    2015-01-01

    EF-hand Ca²⁺-binding proteins are thought to shape the spatiotemporal properties of cellular Ca²⁺ signaling and are prominently expressed in sensory hair cells in the ear. Here, we combined genetic disruption of parvalbumin-α, calbindin-D28k, and calretinin in mice with patch-clamp recording, in vivo physiology, and mathematical modeling to study their role in Ca²⁺ signaling, exocytosis, and sound encoding at the synapses of inner hair cells (IHCs). IHCs lacking all three proteins showed exce...

  11. Removing Hair Safely

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Removing Hair Safely Share Tweet Linkedin Pin it More sharing ... methods of hair removal. back to top Laser Hair Removal In this method, a laser destroys hair ...

  12. A computational model of the auditory periphery for speech and hearing research. I. Ascending path.

    Science.gov (United States)

    Giguère, C; Woodland, P C

    1994-01-01

    A dual analog/digital model of the ascending path through the entire auditory periphery is described. The analog representation consists of the concatenation of electrical circuit submodels for (a) the diffraction of the external ear system; (b) the propagation through the concha and auditory canal; (c) the transmission through the middle ear; (d) the basilar membrane motion and cochlear hydrodynamics; (e) the fast motile mechanism of the outer hair cells; and (f) the neural transduction process of the inner hair cells. Time-domain numerical solutions are obtained by applying the technique of wave digital filtering onto the resulting analog circuit. The present version of the model reproduces the sound pressure gain at the eardrum for lateral sound incidence, the vibration characteristics of the stapes, and the low-frequency attenuation provided by the stapedial muscle. Source elements in the cochlear module provide level-dependent basilar membrane tuning curves leading to dynamic compression of input signals near the characteristic frequency/place. The output is the tonotopic distribution of firing activity in the auditory nerve. A companion article addresses the modeling of the descending paths [C. Giguère and P. C. Woodland, J. Acoust, Soc. Am. 94, 343-349 (1993)]. PMID:8120244

  13. Analysis of cytotoxicity and genotoxicity on E. coli, human blood cells and Allium cepa suggests a greater toxic potential of hair dye.

    Science.gov (United States)

    Maiti, Swati; Sasmal, Kankaayan; Sinha, Sudarson Sekhar; Singh, Mukesh

    2016-02-01

    Pharmaceuticals and personal care products (PPCPs) are among the most important emerging environmental contaminants in recent time. PPCPs include wide range of cosmetics, among which hair dyes, are immensely popular in modern society. However, impact of hair dye and its residual discharged to the environment in relation to human health and ecological imbalance have not been widely studied. Based on the result of initial survey among the group of populations of eastern India, three most popular and commonly used permanent hair dyes are selected. Working sample of dye is prepared as recommended on the instructions booklet of the hair dye. The effect of three dyes is studied on Escherichia coli, human red blood cells (RBC), white blood cells (WBC) and Allium cepa bulbs by growth inhibition, hemolysis, 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and A. cepa micronuclei assays respectively. The Lethal dose (LD) demonstrated significant differences among three dyes and the model systems. In vitro hemolytic assays performed on RBC, and MTT assays on WBC show the cytotoxic effects of hair dye. Significant growth inhibition of E. coli has also been noted. In addition, the root tips of A. cepa treated with the dye have shown major chromosomal abnormalities coupled with cell division retardation. Here low mitotic index confirm cell division retardation. Finally, results of in vitro studies of dye-DNA interactions demonstrate electrostatic interaction. Combing all these results it confirms that hair dyes are cytotoxic and may cause mutagenic effect on living cells irrespective of microbes, plant and animal system. PMID:26544094

  14. Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline.

    Science.gov (United States)

    Sergeyenko, Yevgeniya; Lall, Kumud; Liberman, M Charles; Kujawa, Sharon G

    2013-08-21

    Aging listeners experience greater difficulty understanding speech in adverse listening conditions and exhibit degraded temporal resolution, even when audiometric thresholds are normal. When threshold evidence for peripheral involvement is lacking, central and cognitive factors are often cited as underlying performance declines. However, previous work has uncovered widespread loss of cochlear afferent synapses and progressive cochlear nerve degeneration in noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and Liberman 2009). Here, we characterize age-related cochlear synaptic and neural degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair cell and neuronal function was assessed via distortion product otoacoustic emissions and auditory brainstem responses, respectively. Immunostained cochlear whole mounts and plastic-embedded sections were studied by confocal and conventional light microscopy to quantify hair cells, cochlear neurons, and synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144 weeks) and is seen throughout the cochlea long before age-related changes in thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss, after a delay of several months. Key functional clues to the synaptopathy are available in the neural response; these can be accessed noninvasively, enhancing the possibilities for translation to human clinical characterization. PMID:23966690

  15. Auditory Neuropathy in Two Patients with Generalized Neuropathic Disorder: A Case Report

    Directory of Open Access Journals (Sweden)

    P Ahmadi

    2008-06-01

    Full Text Available Background: Although it is not a new disorder, in recent times we have attained a greater understanding of auditory neuropathy (AN. In this type of hearing impairment, cochlear hair cells function but AN victims suffer from disordered neural transmission in the auditory pathway. The auditory neuropathy result profile often occurs as a part of that of the generalized neuropathic disorders, indicated in approximately 30-40% of all reported auditory neuropathy/auditory dyssynchrony (AN/AD cases, with approximately 80% of patients reporting symptom onset over the age of 15 years. In the present report, the results of audiologic tests (behavioral, physiologic and evoked potentials on two young patients with generalized neuropathy are discussed.Case report: Two brothers, 26 and 17 years old, presented with speech perception weakness and movement difficulties that started at 12 years of age and progressed as time passed. In their last examination, there was a moderate to severe flat audiogram in the older patient and mild low tone loss in the younger one. The major difficulty of the patients was severe speech perception impairment that was not compatible with their hearing thresholds. Paresthesia, sural muscle contraction and pain, and balance disorder were the first symptoms of the older brother. Now he can only move with crutches and his finger muscle tonicity has decreased remarkably, with marked fatigue after a short period of walking. Increasing movement difficulties were noted in his last visit. Visual neuropathy had been reported in repeated visual system examinations for the older brother, with similar, albeit less severe, symptoms in the younger brother.In the present study of these patients, behavioral investigations included pure-tone audiometry and speech discrimination scoring. Physiologic studies consisted Transient Evoked Otoacoustic Emission (TEOAE and acoustic reflexes. Electrophysiologic auditory tests were also performed to determine

  16. Laser assisted hair-removal.

    Science.gov (United States)

    Choudhary, S; Elsaie, M L; Nouri, K

    2009-10-01

    A number of lasers and light devices are now available for the treatment of unwanted hair. The goal of laser hair removal is to damage stem cells in the bulge of the hair follicle by targeting melanin, the endogenous chromophore for laser and light devices utilized to remove hair. The competing chromophores in the skin and hair, oxyhemoglobin and water, have a decreased absorption between 690 nm and 1000 nm, thus making this an ideal range for laser and light sources. Laser hair removal is achieved through follicular unit destruction based on selective photothermolysis. The principle of selective photothermolysis predicts that the thermal injury will be restricted to a given target if there is sufficient selective absorption of light and the pulse duration is shorter than the thermal relaxation time of the target. This review will focus on the mechanisms of laser assisted hair removal and provide an update on the newer technologies emerging in the field of lasers assisted hair removal. PMID:19834437

  17. Tmc gene therapy restores auditory function in deaf mice.

    Science.gov (United States)

    Askew, Charles; Rochat, Cylia; Pan, Bifeng; Asai, Yukako; Ahmed, Hena; Child, Erin; Schneider, Bernard L; Aebischer, Patrick; Holt, Jeffrey R

    2015-07-01

    Genetic hearing loss accounts for up to 50% of prelingual deafness worldwide, yet there are no biologic treatments currently available. To investigate gene therapy as a potential biologic strategy for restoration of auditory function in patients with genetic hearing loss, we tested a gene augmentation approach in mouse models of genetic deafness. We focused on DFNB7/11 and DFNA36, which are autosomal recessive and dominant deafnesses, respectively, caused by mutations in transmembrane channel-like 1 (TMC1). Mice that carry targeted deletion of Tmc1 or a dominant Tmc1 point mutation, known as Beethoven, are good models for human DFNB7/11 and DFNA36. We screened several adeno-associated viral (AAV) serotypes and promoters and identified AAV2/1 and the chicken β-actin (Cba) promoter as an efficient combination for driving the expression of exogenous Tmc1 in inner hair cells in vivo. Exogenous Tmc1 or its closely related ortholog, Tmc2, were capable of restoring sensory transduction, auditory brainstem responses, and acoustic startle reflexes in otherwise deaf mice, suggesting that gene augmentation with Tmc1 or Tmc2 is well suited for further development as a strategy for restoration of auditory function in deaf patients who carry TMC1 mutations. PMID:26157030

  18. Cochlear injury and adaptive plasticity of the auditory cortex

    Directory of Open Access Journals (Sweden)

    ANNA R. eFETONI

    2015-02-01

    Full Text Available Growing evidence suggests that cochlear stressors as noise exposure and aging can induce homeostatic/maladaptive changes in the central auditory system from the brainstem to the cortex. Studies centered on such changes have revealed several mechanisms that operate in the context of sensory disruption after insult (noise trauma, drug- or age-related injury. The oxidative stress is central to current theories of induced sensory neural hearing loss and aging, and interventions to attenuate the hearing loss are based on antioxidant agent. The present review addresses the recent literature on the alterations in hair cells and spiral ganglion neurons due to noise-induced oxidative stress in the cochlea, as well on the impact of cochlear damage on the auditory cortex neurons. The emerging image emphasizes that noise-induced deafferentation and upward spread of cochlear damage is associated with the altered dendritic architecture of auditory pyramidal neurons. The cortical modifications may be reversed by treatment with antioxidants counteracting the cochlear redox imbalance. These findings open new therapeutic approaches to treat the functional consequences of the cortical reorganization following cochlear damage.

  19. Cochlear injury and adaptive plasticity of the auditory cortex.

    Science.gov (United States)

    Fetoni, Anna Rita; Troiani, Diana; Petrosini, Laura; Paludetti, Gaetano

    2015-01-01

    Growing evidence suggests that cochlear stressors as noise exposure and aging can induce homeostatic/maladaptive changes in the central auditory system from the brainstem to the cortex. Studies centered on such changes have revealed several mechanisms that operate in the context of sensory disruption after insult (noise trauma, drug-, or age-related injury). The oxidative stress is central to current theories of induced sensory-neural hearing loss and aging, and interventions to attenuate the hearing loss are based on antioxidant agent. The present review addresses the recent literature on the alterations in hair cells and spiral ganglion neurons due to noise-induced oxidative stress in the cochlea, as well on the impact of cochlear damage on the auditory cortex neurons. The emerging image emphasizes that noise-induced deafferentation and upward spread of cochlear damage is associated with the altered dendritic architecture of auditory pyramidal neurons. The cortical modifications may be reversed by treatment with antioxidants counteracting the cochlear redox imbalance. These findings open new therapeutic approaches to treat the functional consequences of the cortical reorganization following cochlear damage. PMID:25698966

  20. Human Wharton's Jelly Mesenchymal Stem Cells plasticity augments scar-free skin wound healing with hair growth.

    Directory of Open Access Journals (Sweden)

    Vikram Sabapathy

    Full Text Available Human mesenchymal stem cells (MSCs are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL. Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG at optimal concentration can be resourcefully used for labeling of stem cells

  1. Identification of a new plant extract for androgenic alopecia treatment using a non-radioactive human hair dermal papilla cell-based assay

    OpenAIRE

    Jain, Ruchy; Monthakantirat, Orawan; Tengamnuay, Parkpoom; De-Eknamkul, Wanchai

    2016-01-01

    Background Androgenic alopecia (AGA) is a major type of human scalp hair loss, which is caused by two androgens: testosterone (T) and 5α-dihydrotestosterone (5α-DHT). Both androgens bind to the androgen receptor (AR) and induce androgen-sensitive genes within the human hair dermal papilla cells (HHDPCs), but 5α-DHT exhibits much higher binding affinity and potency than T does in inducing the involved androgen-sensitive genes. Changes in the induction of androgen-sensitive genes during AGA are...

  2. Quantitative analysis of the ribbon synapse number of cochlear inner hair cells in C57BL/6J mice using the three-dimensional modeling method.

    Science.gov (United States)

    Liu, Ke; Li, ShuNa; Jiang, XueJun

    2009-09-01

    In mammals, the ribbon synapses of cochlear inner hair cells are a synaptic structure of the first sensory nerve in the pathway of acoustical signal transmission to the acoustic center, and it is directly involved in voice coding and neurotransmitter release. It is difficult to quantitatively analyze the ribbon synaptic number only using an electron microscope, because the ribbon synaptic number is relatively limited and their location is deep. In this study, the specific presynaptic structure-RIBEYE, and non-specific postsynaptic structure-GluR 2 & 3 in C57BL/6J mouse basilar membrane samples were treated by immunofluorescent labeling. Serial section was performed on the samples using a laser scanning confocal microscope, and then the serial sections were used to build three-dimensional models using 3DS MAX software. Each fluorescein color pair indicates one synapse, so the number of ribbon synapses of inner hair cells is obtained. The spatial distribution and the number of ribbon synapses of cochlear inner hair cells were clearly shown in this experiment, and the mean number of ribbon synapses per inner hair cell was 16.10+/-1.03. Our results have demonstrated the number of ribbon synapses is accurately calculated by double immunofluorescent labeling to presynaptic and postsynaptic structures, serial sections obtained using a laser scanning confocal microscope, and three-dimensional modeling obtained using 3DS MAX software. The method above is feasible and has important significance for further exploring the mechanism of sensorineural deafness. PMID:19802738

  3. Disruption of adaptor protein 2mu (AP-2mu) in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing

    NARCIS (Netherlands)

    Jung, S.; Maritzen, T.; Wichmann, C.; Jing, Z.; Neef, A.; Revelo, N.H.; Al-Moyed, H.; Meese, S.; Wojcik, S.M.; Panou, I.; Bulut, H.; Schu, P.; Ficner, R.; Reisinger, E.; Rizzoli, S.O.; Neef, J.; Strenzke, N.; Haucke, V.; Moser, T.

    2015-01-01

    Active zones (AZs) of inner hair cells (IHCs) indefatigably release hundreds of vesicles per second, requiring each release site to reload vesicles at tens per second. Here, we report that the endocytic adaptor protein 2mu (AP-2mu) is required for release site replenishment and hearing. We show that

  4. Quantitative analysis of the ribbon synapse number of cochlear inner hair cells in C57BL/6J mice using the three-dimensional modeling method

    Institute of Scientific and Technical Information of China (English)

    LIU Ke; LI ShuNa; JIANG XueJun

    2009-01-01

    In mammals, the ribbon synapses of cochlear inner hair cells are a synaptic structure of the first sensory nerve in the pathway of acoustical signal transmission to the acoustic center, and it is directly involved in voice coding and neurotransmitter release. It is difficult to quantitatively analyze the ribbon synaptic number only using an electron microscope, because the ribbon synaptic number is relatively limited and their location is deep. In this study, the specific presynaptic structure-RIBEYE, and non-specific postsynaptic structure-GluR 2 & 3 in C57BL/6J mouse basilar membrane samples were treated by immunofluorescent labeling. Serial section was performed on the samples using a laser scanning confocal microscope, and then the serial sections were used to build three-dimensional models using 3DS MAX software. Each fluorescein color pair indicates one synapse, so the number of ribbon synapses of inner hair cells is obtained. The spatial distribution and the number of ribbon synapses of cochlear inner hair cells were clearly shown in this experiment, and the mean number of ribbon synapses per inner hair cell was 16.10±1.03. Our results have demonstrated the number of ribbon synapses is accurately calculated by double immunofluorescent labeling to presynaptic and postsynaptic structures, serial sections obtained using a laser scanning confocal microscope, and three-dimensional modeling obtained using 3DS MAX software. The method above is feasible and has important significance for further exploring the mechanism of sensorineural deafness.

  5. Body Hair

    Science.gov (United States)

    ... and uncomfortable. If you decide to use a hair-removal cream, make sure it says it’s gentle enough for the pubic area. Don’t put on any product that could sting, like aftershave lotion. To help avoid irritation, don’t use products with added dyes or fragrances. If you have more questions about ...

  6. Generation of highly-reactive oxygen species (hROS) is closely related to hair cell damage in rat organ of Corti treated with gentamicin

    OpenAIRE

    Choung, YH; Taura, A.; Pak, K; Choi, SJ; Masuda, M.; Ryan, A.F.

    2009-01-01

    Reactive oxygen species (ROS) have been suggested to play a major role in aminoglycoside-induced hair cell (HC) loss, but are difficult to detect. Moreover, ROS can occur normally in cells where they have roles in metabolism, cell signaling and other processes. Two new probes, aminophenyl fluorescein (APF) and hydroxyphenyl fluorescein (HPF) are dyes which selectively detect highly-reactive oxygen species (hROS), those most associated with cellular damage. We assessed the presence of hROS in ...

  7. Definitive Endoderm Formation from Plucked Human Hair-Derived Induced Pluripotent Stem Cells and SK Channel Regulation

    Directory of Open Access Journals (Sweden)

    Anett Illing

    2013-01-01

    Full Text Available Pluripotent stem cells present an extraordinary powerful tool to investigate embryonic development in humans. Essentially, they provide a unique platform for dissecting the distinct mechanisms underlying pluripotency and subsequent lineage commitment. Modest information currently exists about the expression and the role of ion channels during human embryogenesis, organ development, and cell fate determination. Of note, small and intermediate conductance, calcium-activated potassium channels have been reported to modify stem cell behaviour and differentiation. These channels are broadly expressed throughout human tissues and are involved in various cellular processes, such as the after-hyperpolarization in excitable cells, and also in differentiation processes. To this end, human induced pluripotent stem cells (hiPSCs generated from plucked human hair keratinocytes have been exploited in vitro to recapitulate endoderm formation and, concomitantly, used to map the expression of the SK channel (SKCa subtypes over time. Thus, we report the successful generation of definitive endoderm from hiPSCs of ectodermal origin using a highly reproducible and robust differentiation system. Furthermore, we provide the first evidence that SKCas subtypes are dynamically regulated in the transition from a pluripotent stem cell to a more lineage restricted, endodermal progeny.

  8. Nestin-expressing cells in the developing, mature and noise-exposed cochlear epithelium

    OpenAIRE

    Watanabe, Reiko; Morell, Maria H.; Miller, Josef M.; Kanicki, Ariane; O'Shea, K. Sue; Altschuler, Richard A.; Raphael, Yehoash

    2011-01-01

    The auditory sensory epithelium in non-mammalian vertebrates can replace lost hair cells by transdifferentiation of supporting cells, but this regenerative ability is lost in the mammalian cochlea. Future cell-based treatment of hearing loss may depend on stem cell transplantation or on transdifferentiation of endogenous cells in the cochlea. For both approaches, identification of cells with stem cell features within the mature cochlea may be useful. Here we use a Nestin-β-gal mouse to examin...

  9. Diffuse alopecia areata is associated with intense inflammatory infiltration and CD8+ T cells in hair loss regions and an increase in serum IgE level

    Directory of Open Access Journals (Sweden)

    Ying Zhao

    2012-01-01

    Full Text Available Background: Mechanism leading to an abrupt hair loss in diffuse alopecia areata (AA remains unclear. Aims: To explore the characteristics of diffuse AA and possible factors involved in its pathogenesis. Methods: Clinical and laboratory data of 17 diffuse AA patients and 37 patchy AA patients were analyzed retrospectively. Serum IgE level was evaluated in all diffuse and patchy AA patients, as well as 27 healthy subjects without hair loss to serve as normal control. Univariate analysis was performed using Fisher′s exact test and Wilcoxon rank-sum test. Associations between inflammatory cell infiltration and laboratory values were analyzed using Spearman rank correlation test. Results: The mean age of patients with diffuse AA was 27 years with a mean disease duration of 1.77 months. All of them presented in spring or summer with an acute onset of diffuse hair loss preceded by higher incidence of scalp pruritus. Although no statistically significant difference on the incidence of atopic disease among three groups has been found, serum IgE level in diffuse AA was higher than that in healthy controls, but was comparable to that in patchy AA group. Histopathology of lesional scalp biopsies showed more intense infiltration comprising of mononuclear cells, eosinophils, CD3 + , and CD8 + T cells around hair bulbs in diffuse AA group than in patchy AA group. Moreover, IgE level in diffuse AA patients positively correlated with intensity of infiltration by mononuclear cells, eosinophils, and CD8 + T cells. Conclusions: Hypersensitivity may be involved in pathogenesis of diffuse AA. The acute onset of diffuse AA may be related to intense local inflammatory infiltration of hair loss region and an increase in serum IgE level.

  10. Human mesenchymal stromal cells could deliver erythropoietin and migrate to the basal layer of hair shaft when subcutaneously implanted in a murine model.

    Science.gov (United States)

    Mok, P L; Cheong, S K; Leong, C F; Chua, K H; Ainoon, O

    2012-08-01

    Mesenchymal stromal cells (MSC) are an attractive cell-targeting vehicle for gene delivery. MIDGE (an acronym for Minimalistic, Immunologically Defined Gene Expression) construct is relatively safer than the viral or plasmid expression system as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. The objective of this study was to test the ability of the human MSC (hMSC) to deliver the erythropoietin (EPO) gene in a nude mice model following nucleofection using a MIDGE construct. hMSC nucleofected with MIDGE encoding the EPO gene was injected subcutaneously in Matrigel at the dorsal flank of nude mice. Subcutaneous implantation of nucleofected hMSC resulted in increased hemoglobin level with presence of human EPO in the peripheral blood of the injected nude mice in the first two weeks post-implantation compared with the control groups. The basal layer of the hair shaft in the dermal layer was found to be significantly positive for immunohistochemical staining of a human EPO antibody. However, only a few basal layers of the hair shaft were found to be positively stained for CD105. In conclusion, hMSC harboring MIDGE-EPO could deliver and transiently express the EPO gene in the nude mice model. These cells could be localized to the hair follicle and secreted EPO protein might have possible role in hair regeneration. PMID:22560724

  11. Abnormal hair follicle development and altered cell fate of follicular keratinocytes in transgenic mice expressing ΔNp63α

    OpenAIRE

    Romano, Rose-Anne; Smalley, Kirsten; Liu, Song; Sinha, Satrajit

    2010-01-01

    The transcription factor p63 plays an essential role in epidermal morphogenesis. Animals lacking p63 fail to form many ectodermal organs, including the skin and hair follicles. Although the indispensable role of p63 in stratified epithelial skin development is well established, relatively little is known about this transcriptional regulator in directing hair follicle morphogenesis. Here, using specific antibodies, we have established the expression pattern of ΔNp63 in hair follicle developmen...

  12. Hair care and dyeing.

    Science.gov (United States)

    Draelos, Zoe Diana

    2015-01-01

    Alopecia can be effectively camouflaged or worsened through the use of hair care techniques and dyeing. Proper hair care, involving hair styling and the use of mild shampoos and body-building conditioners, can amplify thinning scalp hair; however, chemical processing, including hair dyeing, permanent waving, and hair straightening, can encourage further hair loss through breakage. Many patients suffering from alopecia attempt to improve their hair through extensive manipulation, which only increases problems. Frequent haircuts to minimize split ends, accompanied by gentle handling of the fragile fibers, is best. This chapter offers the dermatologist insight into hair care recommendations for the alopecia patient. PMID:26370650

  13. Skin, Hair, and Nails

    Science.gov (United States)

    ... distribution of melanin in the cortex of each hair (the same melanin that's found in the epidermis). Hair also contains ... red pigment; people who have blonde or red hair have only a small amount of melanin in their hair. Hair becomes gray when people ...

  14. Neural Hyperactivity of the Central Auditory System in Response to Peripheral Damage

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2016-01-01

    Full Text Available It is increasingly appreciated that cochlear pathology is accompanied by adaptive responses in the central auditory system. The cause of cochlear pathology varies widely, and it seems that few commonalities can be drawn. In fact, despite intricate internal neuroplasticity and diverse external symptoms, several classical injury models provide a feasible path to locate responses to different peripheral cochlear lesions. In these cases, hair cell damage may lead to considerable hyperactivity in the central auditory pathways, mediated by a reduction in inhibition, which may underlie some clinical symptoms associated with hearing loss, such as tinnitus. Homeostatic plasticity, the most discussed and acknowledged mechanism in recent years, is most likely responsible for excited central activity following cochlear damage.

  15. Inhibition of H3K9me2 Reduces Hair Cell Regeneration after Hair Cell Loss in the Zebrafish Lateral Line by Down-Regulating the Wnt and Fgf Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Dongmei eTang

    2016-05-01

    Full Text Available The activation of neuromast supporting cell (SC proliferation leads to hair cell (HC regeneration in the zebrafish lateral line. Epigenetic mechanisms have been reported that regulate HC regeneration in the zebrafish lateral line, but the role of H3K9me2 in HC regeneration after HC loss remains poorly understood. In this study, we focused on the role of H3K9me2 in HC regeneration following neomycin-induced HC loss. To investigate the effects of H3K9me2 in HC regeneration, we took advantage of the G9a/GLP-specific inhibitor BIX01294 that significantly reduces the dimethylation of H3K9. We found that BIX01294 significantly reduced HC regeneration after neomycin-induced HC loss in the zebrafish lateral line. BIX01294 also significantly reduced the proliferation of neuromast cells and led to fewer SCs in the lateral line. In situ hybridization showed that BIX01294 significantly down-regulated the Wnt and Fgf signaling pathways, which resulted in reduced SC proliferation and HC regeneration in the neuromasts of the lateral line. Altogether, our results suggest that down-regulation of H3K9me2 significantly decreases HC regeneration after neomycin-induced HC loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus H3K9me2 plays a critical role in HC regeneration.

  16. Transcriptome profiling of induced hair cells (iHCs) generated by combined expression of Gfi1, Pou4f3 and Atoh1 during embryonic stem cell differentiation.

    Science.gov (United States)

    Costa, Aida; Henrique, Domingos

    2015-12-01

    To gain new insights about the genetic networks controlling hair cell (HC) development, we previously developed a direct genetic programming strategy to generate an inexhaustible supply of HC-like cells (induced HCs, iHCs) in vitro, starting from mouse embryonic stem cells (ESC). We found that combined activity of three transcription factors, Gfi1, Pou4f3, and Atoh1, can program ESC-derived progenitors towards HC fate with efficiencies of 55%-80%. These iHCs express several HC markers and exhibit polarized structures that are highly reminiscent of the mechanosensitive hair bundles, with many microvilli-like stereocilia. Here, we describe the experimental design, methodology, and data validation for the microarray analysis used to characterize the transcriptome profile of iHCs at different stages of their differentiation. This approach based on FACS sorting and microarray analysis revealed a highly similar iHC transcriptome to that of endogenous HCs in vivo. The data obtained in this study is available in the Gene Expression Omnibus (GEO) database (accession number GSE60352). PMID:26697340

  17. Permeation of Fluorophore-Conjugated Phalloidin into Live Hair Cells of the Inner Ear Is Modulated by P2Y Receptors

    OpenAIRE

    Thiede, Benjamin R.; Corwin, Jeffrey T.

    2013-01-01

    Phalloidin, a toxin isolated from the death cap mushroom, Amanita phalloides, binds to filamentous actin with high affinity, and this has made fluorophore-conjugated phalloidin a useful tool in cellular imaging. Hepatocytes take up phalloidin via the liver-specific organic anion transporting polypeptide 1b2, but phalloidin does not permeate most living cells. Rapid entry of styryl dyes into live hair cells has been used to evaluate function, but the usefulness of those fluorescence dyes is li...

  18. A nano-microstructured artificial-hair-cell-type sensor based on topologically graded 3D carbon nanotube bundles

    Science.gov (United States)

    Yilmazoglu, O.; Yadav, S.; Cicek, D.; Schneider, J. J.

    2016-09-01

    A design for a unique artificial-hair-cell-type sensor (AHCTS) based entirely on 3D-structured, vertically aligned carbon nanotube (CNT) bundles is introduced. Standard microfabrication techniques were used for the straightforward micro-nano integration of vertically aligned carbon nanotube arrays composed of low-layer multi-walled CNTs (two to six layers). The mechanical properties of the carbon nanotube bundles were intensively characterized with regard to various substrates and CNT morphology, e.g. bundle height. The CNT bundles display excellent flexibility and mechanical stability for lateral bending, showing high tear resistance. The integrated 3D CNT sensor can detect three-dimensional forces using the deflection or compression of a central CNT bundle which changes the contact resistance to the shorter neighboring bundles. The complete sensor system can be fabricated using a single chemical vapor deposition (CVD) process step. Moreover, sophisticated external contacts to the surroundings are not necessary for signal detection. No additional sensors or external bias for signal detection are required. This simplifies the miniaturization and the integration of these nanostructures for future microsystem set-ups. The new nanostructured sensor system exhibits an average sensitivity of 2100 ppm in the linear regime with the relative resistance change per micron (ppm μm‑1) of the individual CNT bundle tip deflection. Furthermore, experiments have shown highly sensitive piezoresistive behavior with an electrical resistance decrease of up to ∼11% at 50 μm mechanical deflection. The detection sensitivity is as low as 1 μm of deflection, and thus highly comparable with the tactile hair sensors of insects, having typical thresholds on the order of 30–50 μm. The AHCTS can easily be adapted and applied as a flow, tactile or acceleration sensor as well as a vibration sensor. Potential applications of the latter might come up in artificial cochlear systems. In

  19. Proteomic Analysis of Hair Follicles

    Science.gov (United States)

    Ishioka, Noriaki; Terada, Masahiro; Yamada, Shin; Seki, Masaya; Takahashi, Rika; Majima, Hideyuki J.; Higashibata, Akira; Mukai, Chiaki

    2013-02-01

    Hair root cells actively divide in a hair follicle, and they sensitively reflect physical conditions. By analyzing the human hair, we can know stress levels on the human body and metabolic conditions caused by microgravity environment and cosmic radiation. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. During long-term flights, the physiological effects on astronauts include muscle atrophy and bone calcium loss. Furthermore, radiation and psychological effects are important issue to consider. Therefore, an understanding of the effects of the space environment is important for developing countermeasures against the effects experienced by astronauts. In this experiment, we identify functionally important target proteins that integrate transcriptome, mineral metabolism and proteome profiles from human hair. To compare the protein expression data with the gene expression data from hair roots, we developed the protein processing method. We extracted the protein from five strands of hair using ISOGEN reagents. Then, these extracted proteins were analyzed by LC-MS/MS. These collected profiles will give us useful physiological information to examine the effect of space flight.

  20. Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis

    Science.gov (United States)

    Lee, Jayhun; Kang, Sangjo; Lilja, Karin C.; Colletier, Keegan J.; Scheitz, Cornelia Johanna Franziska; Zhang, Ying V.; Tumbar, Tudorita

    2016-01-01

    Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T-cell progenitors. Here we find histone H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells (HFSCs) during G0 quiescence. The level of marks over specific gene promoters did not correlate to mRNA level changes in quiescent HFSCs. Skin hypomethylation during quiescence was necessary for subsequent progression of hair homeostasis (cycle). Inhibiting BMP signal, a known HFSC anti-proliferative factor, elevated HFSC methylation in vivo during quiescence prior to proliferation onset. Furthermore, removal of proliferation factors and addition of BMP4 reduced histone methylases and increased demethylases mRNAs in cultured skin epithelial cells. We conclude that signalling couples hair follicle stem cell quiescence with reduced H3 K4/K9/K27me3 levels for proper tissue homeostasis. PMID:27080563