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Sample records for auditory hair cells

  1. Auditory hair cell innervational patterns in lizards.

    Science.gov (United States)

    Miller, M R; Beck, J

    1988-05-22

    The pattern of afferent and efferent innervation of two to four unidirectional (UHC) and two to nine bidirectional (BHC) hair cells of five different types of lizard auditory papillae was determined by reconstruction of serial TEM sections. The species studies were Crotaphytus wislizeni (iguanid), Podarcis (Lacerta) sicula and P. muralis (lacertids), Ameiva ameiva (teiid), Coleonyx variegatus (gekkonid), and Mabuya multifasciata (scincid). The main object was to determine in which species and in which hair cell types the nerve fibers were innervating only one (exclusive innervation), or two or more hair cells (nonexclusive innervation); how many nerve fibers were supplying each hair cell; how many synapses were made by the innervating fibers; and the total number of synapses on each hair cell. In the species studies, efferent innervation was limited to the UHC, and except for the iguanid, C. wislizeni, it was nonexclusive, each fiber supplying two or more hair cells. Afferent innervation varied both with the species and the hair cell types. In Crotaphytus, both the UHC and the BHC were exclusively innervated. In Podarcis and Ameiva, the UHC were innervated exclusively by some fibers but nonexclusively by others (mixed pattern). In Coleonyx, the UHC were exclusively innervated but the BHC were nonexclusively innervated. In Mabuya, both the UHC and BHC were nonexclusively innervated. The number of afferent nerve fibers and the number of afferent synapses were always larger in the UHC than in the BHC. In Ameiva, Podarcis, and Mabuya, groups of bidirectionally oriented hair cells occur in regions of cytologically distinct UHC, and in Ameiva, unidirectionally oriented hair cells occur in cytologically distinct BHC regions. PMID:3385019

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

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Hair cells are the mechanosensory cells thatconvert sound and motion signals into electrical i m-pulses in cochlear and vestibular end organs of innerear.Although mature mammals nor mally do notgenerate new hair cells,recentin vivoandin vitrostudies have demonstrated mitotic activity and i m-mature-looking hair cells in mammalian vestibularepithelia after exposure to ototoxic drugs[1-3],sug-gesting that vestibular hair cell regeneration inmammals may be inducible.However,the possibil-ity of auditory hair ce...

  7. 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...

  8. 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...

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

    Science.gov (United States)

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

    2016-01-18

    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.

  10. 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.

  11. 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...

  12. 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 ...

  13. Heterotopic synaptic bodies in the auditory hair cells of adult lizards.

    Science.gov (United States)

    Miller, M R; Beck, J

    1987-07-01

    The auditory hair cells of adults of eight species of lizards (three gekkonids: Coleonyx variegatus, Gekko gecko, and Cosymbotus platyurus; two teiids: Ameiva ameiva and Cnemidophorus tigris; one anguid: Celestus costatus; one lacertid: Podarcis (Lacerta) sicula; and one iguanid: Crotaphytus wislizeni) were studied by transmission electron microscopy. Heterotopic synaptic bodies were found in some of the auditory hair cells of all of the above species, occurring frequently in the gekkonids but infrequently in other species. The groups of heterotopic synaptic bodies occurred mainly in the infranuclear cytoplasm between the hair cell nucleus and the hair cell plasma membrane. The groups of synaptic bodies that were close to the hair cell nucleus were usually associated with specialized arrays of rough and smooth endoplasmic reticulum. The numbers of heterotopic synaptic bodies were greatest in the gekkonid species and were especially large in Coleonyx variegatus, where an average of 36.8 synaptic bodies occur in one group. The functional significance of the presence of heterotopic synaptic bodies in the auditory hair cells of adults animals is not known. PMID:2820267

  14. 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.

  15. 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.

  16. Auditory Sensitivity Provided by Self-tuned Critical Oscillations of Hair Cells

    CERN Document Server

    Camalet, S; Jülicher, F; Prost, J; Camalet, Sebastien; Duke, Thomas; Julicher, Frank; Prost, Jacques

    1997-01-01

    We introduce the concept of self-tuned criticality as a general mechanism for signal detection in sensory systems. In the case of hearing, we argue that active amplification of faint sounds is provided by a dynamical system which is maintained at the threshold of an oscillatory instability. This concept can account for the exquisite sensitivity of the auditory system and its wide dynamic range, as well as its capacity to respond selectively to different frequencies. A specific model of sound detection by the hair cells of the inner ear is discussed. We show that a collection of motor proteins within a hair bundle can generate oscillations at a frequency which depends on the elastic properties of the bundle. Simple variation of bundle geometry gives rise to hair cells with characteristic frequencies which span the range of audibility. Tension-gated transduction channels, which primarily serve to detect the motion of a hair bundle, also tune each cell by admitting ions which regulate the motor protein activity....

  17. Inhibition of H3K4me2 Demethylation Protects Auditory Hair Cells from Neomycin-Induced Apoptosis.

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    He, Yingzi; Yu, Huiqian; Cai, Chengfu; Sun, Shan; Chai, Renjie; Li, Huawei

    2015-08-01

    Aminoglycoside-induced hair cell loss is a major cause of hearing impairment in children and deserves more attention in medical research. Epigenetic mechanisms have been shown to protect hair cells from ototoxic drugs. In this study, we focused on the role of dimethylated histone H3K4 (H3K4me2) in hair cell survival. To investigate the effects of lysine-specific demethylase 1 (LSD1)--the histone demethylase primarily responsible for demethylating H3K4me2--on neomycin-induced hair cell loss, isolated cochleae were pretreated with LSD1 inhibitors followed by neomycin exposure. There was a severe loss of hair cells in the organ of Corti after neomycin exposure, and inhibition of LSD1 significantly protected against neomycin-induced hair cell loss. H3K4me2 expression in the nuclei of hair cells decreased after exposure to neomycin, and blocking the decreased expression of H3K4me2 with LSD1 inhibitors prevented hair cell loss. Local delivery of these inhibitors in vivo also protected hair cells from neomycin-induced ototoxicity and maintained the hearing threshold in mice as determined by auditory brain stem response. This inhibition of neomycin-induced apoptosis occurs via reduced caspase-3 activation. Together, our findings demonstrate the protective role for H3K4me2 against neomycin-induced hair cell loss and hearing loss.

  18. 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...

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

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    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

  20. Changes in size and shape of auditory hair cells in vivo during noise-induced temporary threshold shift.

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    Dew, L A; Owen, R G; Mulroy, M J

    1993-03-01

    In this study we describe changes in the size and shape of auditory hair cells of the alligator lizard in vivo during noise-induced temporary threshold shift. These changes consist of a decrease in cell volume, a decrease in cell length and an increase in cell width. We speculate that these changes are due to relaxation of cytoskeletal contractile elements and osmotic loss of intracellular water. We also describe a decrease in the surface area of the hair cell plasmalemma, and speculate that it is related to the endocytosis and intracellular accumulation of cell membrane during synaptic vesicle recycling. Finally we describe an increase in the endolymphatic surface area of the hair cell, and speculate that this could alter the micromechanics of the stereociliary tuft to attenuate the effective stimulus.

  1. 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.

  2. 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 ...

  3. Adaptation Independent Modulation of Auditory Hair Cell Mechanotransduction Channel Open Probability Implicates a Role for the Lipid Bilayer.

    Science.gov (United States)

    Peng, Anthony W; Gnanasambandam, Radhakrishnan; Sachs, Frederick; Ricci, Anthony J

    2016-03-01

    The auditory system is able to detect movement down to atomic dimensions. This sensitivity comes in part from mechanisms associated with gating of hair cell mechanoelectric transduction (MET) channels. MET channels, located at the tops of stereocilia, are poised to detect tension induced by hair bundle deflection. Hair bundle deflection generates a force by pulling on tip-link proteins connecting adjacent stereocilia. The resting open probability (P(open)) of MET channels determines the linearity and sensitivity to mechanical stimulation. Classically, P(open) is regulated by a calcium-sensitive adaptation mechanism in which lowering extracellular calcium or depolarization increases P(open). Recent data demonstrated that the fast component of adaptation is independent of both calcium and voltage, thus requiring an alternative explanation for the sensitivity of P(open) to calcium and voltage. Using rat auditory hair cells, we characterize a mechanism, separate from fast adaptation, whereby divalent ions interacting with the local lipid environment modulate resting P(open). The specificity of this effect for different divalent ions suggests binding sites that are not an EF-hand or calmodulin model. GsMTx4, a lipid-mediated modifier of cationic stretch-activated channels, eliminated the voltage and divalent sensitivity with minimal effects on adaptation. We hypothesize that the dual mechanisms (lipid modulation and adaptation) extend the dynamic range of the system while maintaining adaptation kinetics at their maximal rates.

  4. Auditory sensitivity and the outer hair cell system in the CBA mouse model of age-related hearing loss.

    Science.gov (United States)

    Frisina, Robert D; Zhu, Xiaoxia

    2010-06-01

    Age-related hearing loss is a highly prevalent sensory disorder, from both the clinical and animal model perspectives. Understanding of the neurophysiologic, structural, and molecular biologic bases of age-related hearing loss will facilitate development of biomedical therapeutic interventions to prevent, slow, or reverse its progression. Thus, increased understanding of relationships between aging of the cochlear (auditory portion of the inner ear) hair cell system and decline in overall hearing ability is necessary. The goal of the present investigation was to test the hypothesis that there would be correlations between physiologic measures of outer hair cell function (otoacoustic emission levels) and hearing sensitivity (auditory brainstem response thresholds), starting in middle age. For the CBA mouse, a useful animal model of age-related hearing loss, it was found that correlations between these two hearing measures occurred only for high sound frequencies in middle age. However, in old age, a correlation was observed across the entire mouse range of hearing. These findings have implications for improved early detection of progression of age-related hearing loss in middle-aged mammals, including mice and humans, and distinguishing peripheral etiologies from central auditory system decline.

  5. 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

  6. Basic fibroblast growth factor protects auditory neurons and hair cells from noise exposure and glutamate neurotoxicity

    Institute of Scientific and Technical Information of China (English)

    翟所强; 王大君; 王嘉陵

    2003-01-01

    The purpose of the present study was to determine protectivie effects of basic fibroblast growth factor (bFGF) on cochlear neurons and hair cells in vitro and in vivo. In experiment I, cultured spiral ganglion neurons (SGNs) prepared from P3 mice were exposed to 20mM glutamate for 2 hours before the culture medium was replaced with fresh medium containing 0, 25, 50, and 100 ng/ml bFGF, respectively. Fourteen days later, all cultures were fixed with 4% paraformaldehyde, and stained with 1% toluidine blue. The number of surviving SGNs were counted and the length of SGNs neurites were measured. Exposure to 20 mM glutamate for 24 hours resulted in an inhibition on neurite outgrowth of SGNs and elevated cell death. Treatment of the cultures with bFGF led to promotion of neurite outgrowth and elevated number of surviving SGNs. Effects of bFGF were dose dependent with the highest potency at 100 ng/ml. In experiment Ⅱ, in vivo studies were carried out with guinea pigs in which bFGF or artificial perilymph was perfused into the cochlea to assess possible protective effects of bFGF on cochlear hair cells and compound action potentials(CAP). The CAPs were measured before, immediatly and 48 hours after exposure to noise. Significant differences in CAP were observed (p<0. 05 ) among the bFGF perfused group, control group(t =3. 896 ) and artificial perilymph perfused group (t =2. 520) at 48 hours after noise exposure, Cochleae were removed and hair cell Loss was analyzed in surface preparations prepared from all experimental animals. Acoustic trauma caused loss of 651 and 687 inner hair cells in the control and artificial perilymph perfused group, respectively. In sharp contrast, only 31 inner hair cells were lost in the bFGF perfused ears. Similarly, more outer hair cells died in the control and perilymph perfuesed group (41830 and 41968, respectively) than in the group treated with bFGF (34258). Our results demonstrate that bFGF protected SGNs against glutmate

  7. Down-regulation of msrb3 and destruction of normal auditory system development through hair cell apoptosis in zebrafish.

    Science.gov (United States)

    Shen, Xiaofang; Liu, Fei; Wang, Yingzhi; Wang, Huijun; Ma, Jing; Xia, Wenjun; Zhang, Jin; Jiang, Nan; Sun, Shaoyang; Wang, Xu; Ma, Duan

    2015-01-01

    Hearing defects can significantly influence quality of life for those who experience them. At this time, 177 deafness genes have been cloned, including 134 non-syndromic hearing-loss genes. The methionine sulfoxide reductase B3 (Ahmed et al., 2011) gene (also called DFNB74) is one such newly discovered hearing-loss gene. Within this gene c.265 T>G and c.55 T>C mutations are associated with autosomal recessive hearing loss. However, the biological role and mechanism underlying how it contributes to deafness is unclear. Thus, to better understand this mutation, we designed splicing morpholinos for the purpose of down-regulating msrb3 in zebrafish. Morphants exhibited small, tiny, fused, or misplaced otoliths and abnormal numbers of otoliths. Down-regulation of msrb3 also caused shorter, thinner, and more crowded cilia. Furthermore, L1-8 neuromasts were reduced and disordered in the lateral line system; hair cells in each neuromast underwent apoptosis. Co-injection with human MSRB3 mRNA partially rescued auditory system defects, but mutant MSRB3 mRNA could not. Thus, msrb3 is instrumental for auditory system development in zebrafish and MSRB3-related deafness may be caused by promotion of hair cell apoptosis.

  8. 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...

  9. 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

  10. In vitro protection of auditory hair cells by salicylate from the gentamicin-induced but not neomycin-induced cell loss.

    Science.gov (United States)

    Mazurek, Birgit; Lou, Xiangxin; Olze, Heidi; Haupt, Heidemarie; Szczepek, Agnieszka J

    2012-01-01

    Salicylate has been shown to protect animals and people from the gentamicin-induced hearing loss. The objective of our study was to determine if salicylate is otoprotective in vitro. In this fashion, we wanted to validate the use of explant culture system for future studies on the ototoxicity prevention. In addition, we wanted to find out if salicylate protects from the ototoxicity of other aminoglycosides. As a model, we used the membranous cochlear tissues containing the organ of Corti, spiral limbus and spiral ganglion neurons dissected from the cochleas of p3-p5 Wistar pups. The explants were divided into apical, medial and basal parts and cultured in presence or absence of 100μM gentamicin, 100μM neomycin and 5mM salicylate. Following the tissue fixation and staining with phalloidin-TRITC, the number of inner and outer hair cells (IHCs, OHCs) was scored under the fluorescent microscope. Presence of 5mM salicylate in explants cultures exposed to 100μM gentamicin significantly reduced the loss of IHCs and OHCs, as compared to explants exposed to gentamicin alone. In contrast, neomycin-induced auditory hair cell loss remained unaffected by the presence of salicylate. Our results corroborate earlier in vivo findings and validate the use of cochlear explants for future studies on ototoxicity and its prevention. Moreover, the inability of salicylate to prevent neomycin-induced ototoxicity implies possible differences between the mechanisms of auditory hair cell loss induced by gentamicin and neomycin.

  11. The temporal characteristics of Ca2+ entry through L-type and T-type Ca2+ channels shape exocytosis efficiency in chick auditory hair cells during development.

    Science.gov (United States)

    Levic, Snezana; Dulon, Didier

    2012-12-01

    During development, synaptic exocytosis by cochlear hair cells is first initiated by patterned spontaneous Ca(2+) spikes and, at the onset of hearing, by sound-driven graded depolarizing potentials. The molecular reorganization occurring in the hair cell synaptic machinery during this developmental transition still remains elusive. We characterized the changes in biophysical properties of voltage-gated Ca(2+) currents and exocytosis in developing auditory hair cells of a precocial animal, the domestic chick. We found that immature chick hair cells (embryonic days 10-12) use two types of Ca(2+) currents to control exocytosis: low-voltage-activating, rapidly inactivating (mibefradil sensitive) T-type Ca(2+) currents and high-voltage-activating, noninactivating (nifedipine sensitive) L-type currents. Exocytosis evoked by T-type Ca(2+) current displayed a fast release component (RRP) but lacked the slow sustained release component (SRP), suggesting an inefficient recruitment of distant synaptic vesicles by this transient Ca(2+) current. With maturation, the participation of L-type Ca(2+) currents to exocytosis largely increased, inducing a highly Ca(2+) efficient recruitment of an RRP and an SRP component. Notably, L-type-driven exocytosis in immature hair cells displayed higher Ca(2+) efficiency when triggered by prerecorded native action potentials than by voltage steps, whereas similar efficiency for both protocols was found in mature hair cells. This difference likely reflects a tighter coupling between release sites and Ca(2+) channels in mature hair cells. Overall, our results suggest that the temporal characteristics of Ca(2+) entry through T-type and L-type Ca(2+) channels greatly influence synaptic release by hair cells during cochlear development.

  12. 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

  13. 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...

  14. 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

  15. The effect of hair bundle shape on hair bundle hydrodynamics of inner ear hair cells at low and high frequencies.

    Science.gov (United States)

    Shatz, L F

    2000-03-01

    The relationship between size and shape of the hair bundle of a hair cell in the inner ear and its sensitivity at asymptotically high and low frequencies was determined, thereby extending the results of an analysis of hair bundle hydrodynamics in two dimensions (Freeman and Weiss, 1990. Hydrodynamic analysis of a two-dimensional model for micromechanical resonance of free-standing hair bundles. Hear. Res. 48, 37-68) to three dimensions. A hemispheroid was used to represent the hair bundle. The hemispheroid had a number of advantages: it could represent shapes that range from thin, pencil-like shapes, to wide, flat, disk-like shapes. Also analytic methods could be used in the high frequency range to obtain an exact solution to the equations of motion. In the low frequency range, where an approximate solution was found using boundary element methods, the sensitivity of the responses of hair cells was mainly proportional to the cube of the heights of their hair bundles, and at high frequencies, the sensitivity of the hair cells was mainly proportional to the inverse of their heights. An excellent match was obtained between measurements of sensitivity curves in the basillar papilla of the alligator and bobtail lizards and the model's predictions. These results also suggest why hair bundles of hair cells in vestibular organs which are sensitive to low frequencies have ranges of heights that are an order of magnitude larger than the range of heights of hair bundles of hair cells found in auditory organs.

  16. Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish

    OpenAIRE

    Stawicki, Tamara M.; Hernandez, Liana; Esterberg, Robert; Linbo, Tor; Owens, Kelly N.; Shah, Arish N.; Thapa, Nihal; Roberts, Brock; Cecilia B. Moens; Rubel, Edwin W; Raible, David W.

    2016-01-01

    Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (D...

  17. 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...

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

    Science.gov (United States)

    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

  19. 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...

  20. Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth.

    Science.gov (United States)

    Lelli, Andrea; Michel, Vincent; Boutet de Monvel, Jacques; Cortese, Matteo; Bosch-Grau, Montserrat; Aghaie, Asadollah; Perfettini, Isabelle; Dupont, Typhaine; Avan, Paul; El-Amraoui, Aziz; Petit, Christine

    2016-01-18

    The precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a(-/-)Myo3b(-/-) mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b(-/-) mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a(-/-)Myo3b(-/-) cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a(-/-)Myo3b(-/-) stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping.

  1. 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 ...

  2. MAP3K1 function is essential for cytoarchitecture of the mouse organ of Corti and survival of auditory hair cells

    Directory of Open Access Journals (Sweden)

    Rizwan Yousaf

    2015-12-01

    Full Text Available MAP3K1 is a serine/threonine kinase that is activated by a diverse set of stimuli and exerts its effect through various downstream effecter molecules, including JNK, ERK1/2 and p38. In humans, mutant alleles of MAP3K1 are associated with 46,XY sex reversal. Until recently, the only phenotype observed in Map3k1tm1Yxia mutant mice was open eyelids at birth. Here, we report that homozygous Map3k1tm1Yxia mice have early-onset profound hearing loss accompanied by the progressive degeneration of cochlear outer hair cells. In the mouse inner ear, MAP3K1 has punctate localization at the apical surface of the supporting cells in close proximity to basal bodies. Although the cytoarchitecture, neuronal wiring and synaptic junctions in the organ of Corti are grossly preserved, Map3k1tm1Yxia mutant mice have supernumerary functional outer hair cells (OHCs and Deiters' cells. Loss of MAP3K1 function resulted in the downregulation of Fgfr3, Fgf8, Fgf10 and Atf3 expression in the inner ear. Fgfr3, Fgf8 and Fgf10 have a role in induction of the otic placode or in otic epithelium development in mice, and their functional deficits cause defects in cochlear morphogenesis and hearing loss. Our studies suggest that MAP3K1 has an essential role in the regulation of these key cochlear morphogenesis genes. Collectively, our data highlight the crucial role of MAP3K1 in the development and function of the mouse inner ear and hearing.

  3. 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...

  4. 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 ...

  5. 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...

  6. 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 ...

  7. Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea.

    Science.gov (United States)

    Waqas, Muhammad; Zhang, Shasha; He, Zuhong; Tang, Mingliang; Chai, Renjie

    2016-09-01

    Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atoh1 to regulate hair cell regeneration in the mammalian cochlea. PMID:27527363

  8. 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...

  9. 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...

  10. 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.

  11. 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...

  12. 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...

  13. 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.

  14. Growth factors have a protective effect on neomycin-induced hair cell loss.

    Science.gov (United States)

    Lou, Xiangxin; Yuan, Huihua; Xie, Jing; Wang, Xianliu; Yang, Liangliang; Zhang, Yanzhong

    2015-01-01

    We have demonstrated that selected growth factors are involved in regulating survival and proliferation of progenitor cells derived from the neonatal rat organ of Corti (OC). The protective and regenerative effects of these defined growth factors on the injured organ of Corti were therefore investigated. The organ of Corti dissected from the Wistar rat pups (P3-P5) was split into apical, middle, and basal parts, explanted and cultured with or without neomycin and growth factors. Insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF) protected the inner hair cells (IHCs) and outer hair cells (OHCs) from neomycin ototoxicity. Using EGF, IGF-1, and FGF-2 alone induced no protective effect on the survival of auditory hair cells. Combining 2 growth factors (EGF + IGF-1, EGF + FGF-2, or IGF-1 + FGF-2) gave statistically protective effects. Similarly, combining all three growth factors effectively protected auditory hair cells from the ototoxic insult. None of the growth factors induced regeneration of hair cells in the explants injured with neomycin. Thus various combinations of the three defined factors (IGF-1, FGF-2, and EGF) can protect the auditory hair cells from the neomycin-induced ototoxic damage, but no regeneration was seen. This offers a possible novel approach to the treatment of hearing loss.

  15. 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.

  16. 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.

  17. Immunohistochemical study of hair follicle stem cells in regenerated hair follicles induced by Wnt10b

    Science.gov (United States)

    Zhang, Yiming; Xing, Yizhan; Guo, Haiying; Ma, Xiaogen; Li, Yuhong

    2016-01-01

    The regulation of the periodic regeneration of hair follicles is complicated. Although Wnt10b has been reported to induce hair follicle regeneration, the characteristics of induced hair follicles, especially the target cells of Wnt10b, have not yet been clearly elucidated. Thus, we systematically evaluated the expression and proliferation patterns of Wnt10b-induced hair follicles. We found that Wnt10b promoted the proliferation of hair follicle stem cells from 24 hours after AdWnt10b injection. Seventy-two hours after AdWnt10b injection, cells outside of bulge area began to proliferate. When the induced hair follicle entered full anagen, although the hair follicle stem cells were normal, canonical Wnt signaling was maintained in the hair precortex cells. Our results reveal that the target cells that overexpressed Wnt10b included hair follicle stem cells, hair precortex cells, and matrix cells.

  18. Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish

    Directory of Open Access Journals (Sweden)

    Tamara M. Stawicki

    2016-07-01

    Full Text Available Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (Danio rerio we have found that mutations in multiple cilia genes implicated in intraflagellar transport (dync2h1, wdr35, ift88, and traf3ip, and the ciliary transition zone (cc2d2a, mks1, and cep290 lead to resistance to aminoglycoside-induced hair cell death. These genes appear to have differing roles in hair cells, as mutations in intraflagellar transport genes, but not transition zone genes, lead to defects in kinocilia formation and processes dependent upon hair cell mechanotransduction activity. These mutants highlight a novel role of cilia-associated genes in hair cells, and provide powerful tools for further study.

  19. Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish.

    Science.gov (United States)

    Stawicki, Tamara M; Hernandez, Liana; Esterberg, Robert; Linbo, Tor; Owens, Kelly N; Shah, Arish N; Thapa, Nihal; Roberts, Brock; Moens, Cecilia B; Rubel, Edwin W; Raible, David W

    2016-01-01

    Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (Danio rerio) we have found that mutations in multiple cilia genes implicated in intraflagellar transport (dync2h1, wdr35, ift88, and traf3ip), and the ciliary transition zone (cc2d2a, mks1, and cep290) lead to resistance to aminoglycoside-induced hair cell death. These genes appear to have differing roles in hair cells, as mutations in intraflagellar transport genes, but not transition zone genes, lead to defects in kinocilia formation and processes dependent upon hair cell mechanotransduction activity. These mutants highlight a novel role of cilia-associated genes in hair cells, and provide powerful tools for further study.

  20. Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice.

    Science.gov (United States)

    Wu, Xudong; Indzhykulian, Artur A; Niksch, Paul D; Webber, Roxanna M; Garcia-Gonzalez, Miguel; Watnick, Terry; Zhou, Jing; Vollrath, Melissa A; Corey, David P

    2016-01-01

    Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP-deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction. PMID:27196058

  1. Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Xudong Wu

    Full Text Available Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP-deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction.

  2. 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.

  3. 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

  4. 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

  5. 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...

  6. 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

  7. 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.

  8. Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea

    Science.gov (United States)

    Jin, Yecheng; Ren, Naixia; Li, Shiwei; Fu, Xiaolong; Sun, Xiaoyang; Men, Yuqin; Xu, Zhigang; Zhang, Jian; Xie, Yue; Xia, Ming; Gao, Jiangang

    2016-01-01

    Hair cells (HCs) are mechanosensors that play crucial roles in perceiving sound, acceleration, and fluid motion. The precise architecture of the auditory epithelium and its repair after HC loss is indispensable to the function of organ of Corti (OC). In this study, we showed that Brg1 was highly expressed in auditory HCs. Specific deletion of Brg1 in postnatal HCs resulted in rapid HC degeneration and profound deafness in mice. Further experiments showed that cell-intrinsic polarity of HCs was abolished, docking of outer hair cells (OHCs) by Deiter’s cells (DCs) failed, and scar formation in the reticular lamina was deficient. We demonstrated that Brg1 ablation disrupted the Gαi/Insc/LGN and aPKC asymmetric distributions, without overt effects on the core planer cell polarity (PCP) pathway. We also demonstrated that Brg1-deficient HCs underwent apoptosis, and that leakage in the reticular lamina caused by deficient scar formation shifted the mode of OHC death from apoptosis to necrosis. Together, these data demonstrated a requirement for Brg1 activity in HC development and suggested a role for Brg1 in the proper cellular structure formation of HCs. PMID:27255603

  9. 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.

  10. 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.

  11. 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.

  12. 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 ...

  13. An electrical tuning mechanism in turtle cochlear hair cells.

    Science.gov (United States)

    Crawford, A C; Fettiplace, R

    1981-03-01

    1. Intracellular recordings were made from single cochlear hair cells in the isolated half-head of the turtle. The electrical responses of the cells were recorded under two conditions: (a) when the ear was stimulated with low-intensity tones of different frequencies and (b) when current steps were injected through the intracellular electrode. The aim of the experiments was to evaluate the extent to which the cochlea's frequency selectivity could be accounted for by the electrical properties of the hair cells.2. At low levels of acoustic stimulation, the amplitude of the hair cell's receptor potential was proportional to sound pressure. The linear tuning curve, which is defined as the sensitivity of the cell as a function of frequency when the cell is operating in its linear range, was measured for a number of hair cells with characteristic frequencies from 86 Hz to 425 Hz.3. A rectangular current passed into a hair cell elicited a membrane potential change consisting of a damped oscillation superimposed on a step. Small currents produced symmetrical oscillations at the beginning and end of the pulse. Larger currents increased the initial ringing frequency if depolarizing and decreased it if hyperpolarizing.4. For small currents the frequency of the oscillations and the quality factor (Q) of the electrical resonance derived from the decay of the oscillations were close to the characteristic frequency and Q of the hair-cell linear tuning curve obtained from sound presentations.5. The hair cell's membrane potential change to small-current pulses or low-intensity tone bursts could be largely described by representing the hair cell as a simple electrical resonator consisting of an inductance, resistor and capacitor.6. When step displacements of 29-250 nm were applied to a micropipette, placed just outside a hair cell in the basilar papilla, an initial periodic firing of impulses could be recorded from single fibres in the auditory nerve. Currents of up to 1 nA, injected

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

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    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.

  15. Significance of the resting angles of hair-cell bundles for Hopf bifurcation criticality

    Science.gov (United States)

    Kim, Kyung-Joong; Ahn, Kang-Hun

    2016-08-01

    We investigate the significance of the inclined angle of a hair bundle at equilibrium. We find that, while the angle gives a geometrical conversion factor between the bundle deflection and the ion channel displacement, it also controls the dynamics of the bundle. We show that a Hopf bifurcation, which enhances sensitivity, can be driven by the geometrical factor. However, existing experimental data indicate that mammalian auditory hair-cell bundles are located far away from the Hopf bifurcation point, suggesting that the high sensitivity of mammalian hearing might come from other mechanisms.

  16. 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...

  17. Regeneration of stereocilia of hair cells by forced Atoh1 expression in the adult mammalian cochlea.

    Directory of Open Access Journals (Sweden)

    Shi-Ming Yang

    Full Text Available The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60-70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.

  18. 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...

  19. 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.

  20. 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

  1. Treatment with Piribedil and Memantine Reduces Noise-Induced Loss of Inner Hair Cell Synaptic Ribbons

    Science.gov (United States)

    Altschuler, Richard A.; Wys, Noel; Prieskorn, Diane; Martin, Cathy; DeRemer, Susan; Bledsoe, Sanford; Miller, Josef M.

    2016-01-01

    Noise overstimulation can induce loss of synaptic ribbons associated with loss of Inner Hair CellAuditory Nerve synaptic connections. This study examined if systemic administration of Piribedil, a dopamine agonist that reduces the sound evoked auditory nerve compound action potential and/or Memantine, an NMDA receptor open channel blocker, would reduce noise-induced loss of Inner Hair Cell ribbons. Rats received systemic Memantine and/or Piribedil for 3 days before and 3 days after a 3 hour 4 kHz octave band noise at 117 dB (SPL). At 21 days following the noise there was a 26% and 38% loss of synaptic ribbons in regions 5.5 and 6.5 mm from apex, respectively, elevations in 4-, 8- and 20 kHz tonal ABR thresholds and reduced dynamic output at higher intensities of stimulation. Combined treatment with Piribedil and Memantine produced a significant reduction in the noise-induced loss of ribbons in both regions and changes in ABR sensitivity and dynamic responsiveness. Piribedil alone gave significant reduction in only the 5.5 mm region and Memantine alone did not reach significance in either region. Results identify treatments that could prevent the hearing loss and hearing disorders that result from noise-induced loss of Inner Hair CellAuditory Nerve synaptic connections. PMID:27686418

  2. 压力波对豚鼠耳蜗血管纹、毛细胞心钠素免疫活性改变的研究%Change of Atrial Natriuretic Peptides Immunoreactivity in Stria Vascularis and Hair Cells of Cochlear and Correlation Study of Auditory Threshold Shift After Shock Wave

    Institute of Scientific and Technical Information of China (English)

    陈合新; 邱建华; 王锦玲

    2000-01-01

    目的为探讨压力波的致聋机理,对豚鼠耳蜗血管纹(SV)、毛细胞(HC)中心钠素免疫活性(ANP-IR)的改变及与听阈阈移的相关性进行研究。方法采用免疫细胞化学(ABC法)法、图像分析听性脑干反应测听技术(ABR)对压力波暴露后不同时间分组的豚鼠耳蜗SV、HC中ANP-IR产物进行检测。结果压力波暴露后6、12、24h和48h组SV组织中ANP-IR光密度值较对照组均有明显的差异(P<0.05),其中24h组最高;冲击波暴露后6、12、24h组内毛细胞(IHC)中ANP-IR阳性产物的光密度值较对照组明显增高(P<0.05),其中以12 h组最高。二者的变化均与听阈阈移有明显的正相关性(r1=0.8175,P>0.05;r2=0.9185,P>0.05)。而外毛细胞(OHC)中ANP-IR阳性产物变化不明显。结论压力波暴露后,SV组织中ANP的增高可能是内耳的一种代偿机制;IHC和OHC中ANP-IR的变化可能是冲击波对其损伤机制的不同表现。%Objective In order to investigate the effects of shock wave on atrial natriuretic peptides immunoreactivity in the stria vascularis and hair cells of cochlear and correlation of auditory threshold shift,to study the mechanism of deafness caused by blast trauma. Methods After shock wave, different groups of guinea pigs were studied by ABC immunohistochemistry, image analysis and auditory brainstem response. Results ANP - IR optic density in experimental group was higher than that of control in the stria vascularis and inner hair cells. The change of ANP- IR optic density was directy correlated with ABR threshold shift (r2 =0.9185. P2<0.05). There was no change of ABR and ANP - IR optic density on outer hair cells. Conclusion The change of ANP in the stria vascularis may be a compensatory mechanism to heating lose caused by shock wave; ANP in inner cells may be a pathological manifestation of shock wave. The changes of ANP - IR in outer cells may be a false appearance, it was the shock wave which

  3. THE COCHLEAR AMPLIFIER:IS IT HAIR BUNDLE MOTION OF OUTER HAIR CELLS?

    Institute of Scientific and Technical Information of China (English)

    LI Yi; He David Z

    2014-01-01

    Cochlear outer hair cells (OHCs) are involved in a mechanical feedback loop in which the fast somatic motility of OHCs is required for cochlear amplification. Alternatively, amplification is thought to arise from active hair bundle movements ob-served in non-mammalian hair cells. We measured the voltage-evoked hair bundle motions in the gerbil cochlea to determine if such movements are also present in mammalian OHCs. The OHCs displayed a large hair bundle movement that was not based on mechanotransducer channels but based on somatic motility. Significantly, bundle movements were able to generate radial motion of the tectorial membrane in situ. This result implies that the motility-associated hair bundle motion may be part of the cochlear amplifier.

  4. 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.

  5. A descriptive model of the receptor potential nonlinearities generated by the hair cell mechanoelectrical transducer.

    Science.gov (United States)

    Lukashkin, A N; Russell, I J

    1998-02-01

    This paper describes a model for generating the hair cell receptor potential based on a second-order Boltzmann function. The model includes only the resistive elements of the hair cell membranes with batteries across them and the series resistance of the external return path of the transducer current through the tissue of the cochlea. The model provides a qualitative description of signal processing by the hair cell transducer and shows that the nonlinearity of the hair cell transducer can give rise to nonlinear phenomena, such as intermodulation distortion products and two-tone suppression with patterns similar to those which have been recorded from the peripheral auditory system. Particular outcomes of the model are the demonstration that two-tone suppression depends not on the saturation of the receptor current, but on the behaviour of the hair cell transducer function close to the operating point. The model also shows that there is non-monotonic growth and phase change for any spectral component, but not for the fundamental of the receptor potential. PMID:9479750

  6. TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear

    OpenAIRE

    Pan, Bifeng; Géléoc, Gwenaelle S.; Asai, Yukako; Horwitz, Geoffrey C.; Kurima, Kiyoto; Ishikawa, Kotaro; Kawashima, Yoshiyuki; Griffith, Andrew J; Holt, Jeffrey R.

    2013-01-01

    Sensory transduction in auditory and vestibular hair cells requires expression of transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are components of the mechanosensitive ion channels that convert mechanical information into electrical signals, we recorded whole-cell and single-channel currents from mouse hair cells that expressed Tmc1, Tmc2 or mutant Tmc1. Cells that expressed mutant Tmc1 had ...

  7. Gene and stem cell therapy of the hair follicle.

    Science.gov (United States)

    Hoffman, Robert M

    2005-01-01

    The hair follicle is a highly complex appendage of the skin containing a multiplicity of cell types. The follicle undergoes constant cycling through the life of the organism including growth and resorption with growth dependent on specific stem cells. The targeting of the follicle by genes and stem cells to change its properties, in particular, the nature of the hair shaft is discussed. Hair follicle delivery systems are described such as liposomes and viral vectors for gene therapy. The nature of the hair follicle stem cells is discussed, in particular, its pluripotency.

  8. 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.

  9. 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...

  10. Slow motility in hair cells of the frog amphibian papilla: Ca2+-dependent shape changes.

    Science.gov (United States)

    Farahbakhsh, Nasser A; Narins, Peter M

    2006-02-01

    We investigated the process of slow motility in non-mammalian auditory hair cells by recording the time course of shape change in hair cells of the frog amphibian papilla. The tall hair cells in the rostral segment of this organ, reported to be the sole recipients of efferent innervation, were found to shorten in response to an increase in the concentration of the intracellular free calcium. These shortenings are composed of two partially-overlapping phases: an initial rapid iso-volumetric contraction, followed by a slower length decrease accompanied with swelling. It is possible to unmask the iso-volumetric contraction by delaying the cell swelling with the help of K+ or Cl- channel inhibitors, quinine or furosemide. Furthermore, it appears that the longitudinal contraction in these cells is Ca2+-calmodulin-dependent: in the presence of W-7, a calmodulin inhibitor, only a slow, swelling phase could be observed. These findings suggest that amphibian rostral AP hair cells resemble their mammalian counterparts in expressing both a Ca2+-calmodulin-dependent contractile structure and an "osmotic" mechanism capable of mediating length change in response to extracellular stimuli. Such a mechanism might be utilized by the efferent neurotransmitters for adaptive modulation of mechano-electrical transduction, sensitivity enhancement, frequency selectivity, and protection against over-stimulation.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Quanwen Liu

    2016-01-01

    Full Text Available 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 bundles. The hair-cell-like cells exhibited rapid permeation of FM1-43FX. The whole-cell patch-clamp technique was used to measure the membrane currents of cells differentiated for 7 days on chicken utricle stromal cells and analyze the biophysical properties of the hair-cell-like cells by recording membrane properties of cells. The results suggested that the hair-cell-like cells derived from inner ear multipotent cells were functional following differentiation in an enabling environment.

  13. LKB1 Is Required for the Development and Maintenance of Stereocilia in Inner Ear Hair Cells in Mice.

    Directory of Open Access Journals (Sweden)

    Yuqin Men

    Full Text Available The LKB1 gene, which encodes a serine/threonine kinase, was discovered to play crucial roles in cell differentiation, proliferation, and the establishment of cell polarity. In our study, LKB1 conditional knockout mice (Atoh1-LKB1-/- mice were generated to investigate LKB1 function in the inner ear. Tests of auditory brainstem response and distortion product otoacoustic emissions revealed significant decreases in the hearing sensitivities of the Atoh1-LKB1-/- mice. In Atoh1-LKB1-/- mice, malformations of hair cell stereocilliary bundles were present as early as postnatal day 1 (P1, a time long before the maturation of the hair cell bundles. In addition, we also observed outer hair cell (OHC loss starting at P14. The impaired stereocilliary bundles occurred long before the presence of hair cell loss. Stereociliary cytoskeletal structure depends on the core actin-based cytoskeleton and several actin-binding proteins. By Western blot, we examined actin-binding proteins, specifically ERM (ezrin/radixin/moesin proteins involved in the regulation of the actin cytoskeleton of hair cell stereocilia. Our results revealed that the phosphorylation of ERM proteins (pERM was significantly decreased in mutant mice. Thus, we propose that the decreased pERM may be a key factor for the impaired stereocillia function, and the damaged stereocillia may induce hair cell loss and hearing impairments. Taken together, our data indicates that LKB1 is required for the development and maintenance of stereocilia in the inner ear.

  14. 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.

  15. Semicircular canals circumvent brownian motion overload of mechanoreceptor hair cells

    NARCIS (Netherlands)

    Muller, Mees; Heeck, Kier; Elemans, Coen P.H.

    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 (4

  16. 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...

  17. 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.

  18. An Analogue VLSI Implementation of the Meddis Inner Hair Cell Model

    Directory of Open Access Journals (Sweden)

    McEwan Alistair

    2003-01-01

    Full Text Available The Meddis inner hair cell model is a widely accepted, but computationally intensive computer model of mammalian inner hair cell function. We have produced an analogue VLSI implementation of this model that operates in real time in the current domain by using translinear and log-domain circuits. The circuit has been fabricated on a chip and tested against the Meddis model for (a rate level functions for onset and steady-state response, (b recovery after masking, (c additivity, (d two-component adaptation, (e phase locking, (f recovery of spontaneous activity, and (g computational efficiency. The advantage of this circuit, over other electronic inner hair cell models, is its nearly exact implementation of the Meddis model which can be tuned to behave similarly to the biological inner hair cell. This has important implications on our ability to simulate the auditory system in real time. Furthermore, the technique of mapping a mathematical model of first-order differential equations to a circuit of log-domain filters allows us to implement real-time neuromorphic signal processors for a host of models using the same approach.

  19. Distinguishing hair cell from neural potentials recorded at the round window.

    Science.gov (United States)

    Forgues, Mathieu; Koehn, Heather A; Dunnon, Askia K; Pulver, Stephen H; Buchman, Craig A; Adunka, Oliver F; Fitzpatrick, Douglas C

    2014-02-01

    Almost all patients who receive cochlear implants have some acoustic hearing prior to surgery. Electrocochleography (ECoG), or electrophysiological measures of cochlear response to sound, can identify remaining auditory nerve activity that is the basis for this residual hearing and can record potentials from hair cells that are no longer functionally connected to nerve fibers. The ECoG signal is therefore complex, being composed of both hair cell and neural signals. To identify signatures of different sources in the recorded potentials, we collected ECoG data across frequency and intensity from the round window of gerbils before and after treatment with kainic acid, a neurotoxin. Distortions in the recorded waveforms were produced by different sources over different ranges of frequency and intensity. In response to tones at low frequencies and low-to-moderate intensities, the major source of distortion was from neural phase-locking that was sensitive to kainic acid. At high intensities at all frequencies, the distortion was not sensitive to kainic acid and was consistent with asymmetric saturation of the hair cell transducer current. In addition to loss of phase-locking, changes in the envelope after kainic acid treatment indicate that sustained neural firing combines with receptor potentials from hair cells to produce the envelope of the response to tones. These results provide baseline data to interpret comparable recordings from human cochlear implant recipients. PMID:24133227

  20. 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.

  1. Acute mechanical overstimulation of isolated outer hair cells causes changes in intracellular calcium levels without shape changes.

    Science.gov (United States)

    Fridberger, A; Ulfendahl, M

    1996-01-01

    Impaired auditory function following acoustic overstimulation, or noise, is mainly reported to be accompanied by cellular changes such as damage to the sensory hair bundles, but changes in the cell bodies of the outer hair cells have also been described. To investigate more closely the immediate cellular responses to overstimulation, isolated guinea pig outer hair cells were subjected to a 200 Hz oscillating water jet producing intense mechanical stimulation. The water jet was aimed at the cell body of the isolated outer hair cell. Cell shape changes were studied using video microscopy, and intracellular calcium concentration changes were monitored by means of the fluorescent calcium indicator Fluo-3. Cells exposed to a high-intensity stimulus showed surprisingly small light-microscopical alterations. The cytoplasmic calcium concentration increased in most cells, although some cells appeared very resistant to the mechanical stress. No correlation could be found be tween the calcium concentration changes and the cell length. The changes in calcium concentration reported here are suggested to be involved in the long-term pathogenesis of noise-induced hair cell damage.

  2. 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.

  3. 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 ...

  4. Vestibular evoked myogenic potentials are heavily dependent on type I hair cell activity of the saccular macula in guinea pigs.

    Science.gov (United States)

    Lue, June-Horng; Day, An-Shiou; Cheng, Po-Wen; Young, Yi-Ho

    2009-01-01

    This study applied the vestibular evoked myogenic potential (VEMP) test to guinea pigs coupled with electronic microscopic examination to determine whether VEMPs are dependent on type I or II hair cell activity of the saccular macula. An amount of 0.05 ml of gentamicin (40 mg/ml) was injected directly overlaying, but not through, the round window membrane of the left ear in guinea pigs.One week after surgery, auditory brainstem response test revealed normal responses in 12 animals (80%), and elevated thresholds in 3 animals (20%). The VEMP test using click stimulation showed absent responses in all 15 animals (100%). Another 6 gentamicin-treated animals underwent the VEMP test using galvanic stimulation and all 6 also displayed absent responses. Ultrathin sections of the saccular macula in the gentamicin-treated ears displayed morphologic alterations in type I or II hair cells, including shrinkage and/or vacuolization in the cytoplasm, increased electron density of the cytoplasm and nuclear chromatin, and cellular lucency. However, extrusion degeneration was rare and only present in type II hair cells. Quantitative analysis demonstrated that the histological density of intact type I hair cells was 1.1 +/- 1.2/4000 microm(2) in the gentamicin-treated ears, showing significantly less than that in control ears (4.5 +/- 1.8/4000 microm(2)). However, no significant difference was observed in the densities of intact type II hair cells and supporting cells between treated and control ears. Furthermore, the calyx terminals surrounding the damaged type I hair cells were swollen and disrupted, while the button afferents contacting the damaged type II hair cells were not obviously deformed. Based on the above results, we therefore conclude that VEMPs are heavily dependent on type I hair cell activity of the saccular macula in guinea pigs.

  5. Introduction to Hair-Follicle-Associated Pluripotent Stem Cells.

    Science.gov (United States)

    Hoffman, Robert M

    2016-01-01

    Nestin-expressing stem cells of the hair follicle, discovered by our laboratory, have been shown to be able to form outer-root sheaths of the follicle as well as neurons and many other non-follicle cell types. We have termed the nestin-expressing stem cells of the hair follicle as hair-follicle-associated pluripotent (HAP) stem cells. We have shown that the HAP stem cells from the hair follicle can effect the repair of peripheral nerve and spinal cord injury. The hair follicle stem cells differentiate into neuronal and glial cells after transplantation to the injured peripheral nerve and spinal cord, and enhance injury repair and locomotor recovery. When the excised hair follicle with its nerve stump was placed in Gelfoam(®) 3D histoculture, HAP stem cells grew and extended the hair follicle nerve which consisted of βIII-tubulin-positive fibers with F-actin expression at the tip. These findings indicate that βIII-tubulin-positive fibers elongating from the whisker follicle sensory nerve stump were growing axons. The growing whisker sensory nerve was highly enriched in HAP stem cells, which appeared to play a major role in its elongation and interaction with other nerves in 3D Gelfoam(®) histoculture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. These results suggest that a major function of the HAP stem cells in the hair follicle is for growth of the follicle sensory nerve. Recently, we have shown that HAP stem cells can differentiate into beating cardiac muscle cells. HAP stem cells have critical advantages for regenerative medicine over embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in that they are highly accessible from each patient, thereby eliminating immunological issues since they are autologous, require no genetic manipulation, are non-tumorigenic, and do not present ethical issues.

  6. 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

  7. 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...

  8. Hair cell mechano-transduction : Its influence on the gross mechanical characteristics of a hair cell sense organ

    NARCIS (Netherlands)

    vanNetten, SM

    1997-01-01

    The complex mechanical behaviour of a hair cell bundle appears to be a direct consequence of the gating forces on the individual transduction channels. The mechanical molecular interactions involved in transduction channel gating, therefore, also bear a reciprocal influence, via the hair bundles; on

  9. 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 ...

  10. 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 ...

  11. Ecabet sodium alleviates neomycin-induced hair cell damage.

    Science.gov (United States)

    Rah, Yoon Chan; Choi, June; Yoo, Myung Hoon; Yum, Gunhwee; Park, Saemi; Oh, Kyoung Ho; Lee, Seung Hoon; Kwon, Soon Young; Cho, Seung Hyun; Kim, Suhyun; Park, Hae-Chul

    2015-12-01

    Ecabet sodium (ES) is currently applied to some clinical gastrointestinal disease primarily by the inhibition of the ROS production. In this study, the protective role of ES was evaluated against the neomycin-induced hair cell loss using zebrafish experimental animal model. Zebrafish larvae (5-7 dpf), were treated with each of the following concentrations of ES: 5, 10, 20, 40, and 80 μg/mL for 1 h, followed by 125 μM neomycin for 1h. The positive control group was established by 125 μM neomycin-only treatment (1h) and the negative control group with no additional chemicals was also established. Hair cells inside four neuromasts ( SO1, SO2, O1, OC1) were assessed using fluorescence microscopy (n = 10). Hair cell survival was calculated as the mean number of viable hair cells for each group. Apoptosis and mitochondrial damage were investigated using special staining (TUNEL and DASPEI assay, respectively), and compared among groups. Ultrastructural changes were evaluated using scanning electron microscopy. Pre-treatment group with ES increased the mean number of viable hair cells as a dose-dependent manner achieving almost same number of viable hair cells with 40 μM/ml ES treatment (12.98 ± 2.59 cells) comparing to that of the negative control group (14.15 ± 1.39 cells, p = 0.72) and significantly more number of viable hair cells than that of the positive control group (7.45 ± 0.91 cells, p neomycin treatment than the negative control group and significantly decreased down to 105% with the pre-treatment with 40 μM/ml ES (n = 40, p = 0.04). A significantly less number of TUNEL-positive cells (reflecting apoptosis, p neomycin-induced hair cell loss possibly by reducing apoptosis, mitochondrial damages, and the ROS generation.

  12. 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...

  13. 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

  14. Semicircular canals circumvent Brownian Motion overload of mechanoreceptor hair cells

    DEFF Research Database (Denmark)

    Muller, Mees; Heeck, Kier; Elemans, Coen P H

    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...... to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors...

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

    DEFF Research Database (Denmark)

    Muller, Mees; Heeck, Kier; Elemans, Coen P H

    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 (hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above...... differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (

  16. 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.

  17. 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...

  18. 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 (mechanoreceptors of the SCC. PMID:27448330

  19. 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

  20. 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...

  1. Transmitter release from cochlear hair cells is phase locked to cyclic stimuli of different intensities and frequencies.

    Science.gov (United States)

    Goutman, Juan D

    2012-11-21

    The auditory system processes time and intensity through separate brainstem pathways to derive spatial location as well as other salient features of sound. The independent coding of time and intensity begins in the cochlea, where afferent neurons can fire action potentials at constant phase throughout a wide range of stimulus intensities. We have investigated time and intensity coding by simultaneous presynaptic and postsynaptic recording at the hair cell-afferent synapse from rats. Trains of depolarizing steps to the hair cell were used to elicit postsynaptic currents that occurred at constant phase for a range of membrane potentials over which release probability varied significantly. To probe the underlying mechanisms, release was examined using single steps to various command voltages. As expected for vesicular release, first synaptic events occurred earlier as presynaptic calcium influx grew larger. However, synaptic depression produced smaller responses with longer first latencies. Thus, during repetitive hair cell stimulation, as the hair cell is more strongly depolarized, increased calcium channel gating hurries transmitter release, but the resulting vesicular depletion produces a compensatory slowing. Quantitative simulation of ribbon function shows that these two factors varied reciprocally with hair cell depolarization (stimulus intensity) to produce constant synaptic phase. Finally, we propose that the observed rapid vesicle replenishment would help maintain the vesicle pool, which in turn would equilibrate with the stimulus intensity (and therefore the number of open Ca(2+) channels), so that for trains of different levels the average phase will be conserved. PMID:23175853

  2. 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

  3. 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.

  4. 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...

  5. 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...

  6. Coenzyme Q10 protects hair cells against aminoglycoside.

    Directory of Open Access Journals (Sweden)

    Kazuma Sugahara

    Full Text Available It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10 is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group. In the neomycin group, utricles were cultured with neomycin (1 mM to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM. Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

  7. 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...

  8. 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

  9. 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

  10. 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.

  11. Ephrin A2 protein expression in the regeneration and plasticity of cochlear hair cells in chicken following kanamycin ototoxicity

    Institute of Scientific and Technical Information of China (English)

    Jia Yu; Mingliang Xiang; Hao Wu; Chenling Shen

    2012-01-01

    The results from this study showed that the thresholds of brainstem auditory-evoked potentials peak following 10 successive days of intramuscular injection of Roman chickens with kanamycin, starting 3 days after birth. Fluorescence immunohistochemistry analysis revealed few ganglion cells positively labeled for Ephrin A2 in the cochlea of experimental chickens from 2 days before until 7 days after the last kanamycin injection. The number of Ephrin A2-positive ganglion cell bodies was increased at 15 days after the last injection and was similar to that in normal chickens at 30 days following the cessation of kanamycin treatment. These experimental findings indicate that Ephrin A2 protein expression in the acoustic ganglia is synchronized with the connection damage and regeneration of cochlear hair cells after kanamycin exposure. Ephrin A2 may play an important role in the regeneration and plasticity of cochlear hair cells in the chick cochlea following kanamycin ototoxicity.

  12. 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.

  13. 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

  14. 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...

  15. 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...

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

    Directory of Open Access Journals (Sweden)

    Mees Muller

    Full Text Available 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 (< 10 μm vs. <400 nm. We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC.

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

    Science.gov (United States)

    Muller, Mees; Heeck, Kier; Elemans, Coen P H

    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 (< 10 μm vs. <400 nm). We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz) signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC. PMID:27448330

  18. 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 ...

  19. Two modes of release shape the postsynaptic response at the inner hair cell ribbon synapse.

    Science.gov (United States)

    Grant, Lisa; Yi, Eunyoung; Glowatzki, Elisabeth

    2010-03-24

    Cochlear inner hair cells (IHCs) convert sounds into receptor potentials and via their ribbon synapses into firing rates in auditory nerve fibers. Multivesicular release at individual IHC ribbon synapses activates AMPA-mediated EPSCs with widely ranging amplitudes. The underlying mechanisms and specific role for multivesicular release in encoding sound are not well understood. Here we characterize the waveforms of individual EPSCs recorded from afferent boutons contacting IHCs and compare their characteristics in immature rats (postnatal days 8-11) and hearing rats (postnatal days 19-21). Two types of EPSC waveforms were found in every recording: monophasic EPSCs, with sharp rising phases and monoexponential decays, and multiphasic EPSCs, exhibiting inflections on rising and decaying phases. Multiphasic EPSCs exhibited slower rise times and smaller amplitudes than monophasic EPSCs. Both types of EPSCs had comparable charge transfers, suggesting that they were activated by the release of similar numbers of vesicles, which for multiphasic EPSCs occurred in a less coordinated manner. On average, a higher proportion of larger, monophasic EPSCs was found in hearing compared to immature rats. In addition, EPSCs became significantly faster with age. The developmental increase in size and speed could improve auditory signaling acuity. Multiphasic EPSCs persisted in hearing animals, in some fibers constituting half of the EPSCs. The proportion of monophasic versus multiphasic EPSCs varied widely across fibers, resulting in marked heterogeneity of amplitude distributions. We propose that the relative contribution of two modes of multivesicular release, generating monophasic and multiphasic EPSCs, may underlie fundamental characteristics of auditory nerve fibers.

  20. 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.

  1. Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration.

    Directory of Open Access Journals (Sweden)

    Sang Goo Lee

    Full Text Available Unlike mammals, the non-mammalian vertebrate inner ear can regenerate the sensory cells, hair cells, either spontaneously or through induction after hair cell loss, leading to hearing recovery. The mechanisms underlying the regeneration are poorly understood. By microarray analysis on a chick model, we show that chick hair cell regeneration involves the activation of proliferation genes and downregulation of differentiation genes. Both MYC and FGF are activated in chick hair cell regeneration. Using a zebrafish lateral line neuromast hair cell regeneration model, we show that the specific inhibition of Myc or Fgf suppresses hair cell regeneration, demonstrating that both pathways are essential to the process. Rapid upregulation of Myc and delayed Fgf activation during regeneration suggest a role of Myc in proliferation and Fgf in differentiation. The dorsal-ventral pattern of fgfr1a in the neuromasts overlaps with the distribution of hair cell precursors. By laser ablation, we show that the fgfr1a-positive supporting cells are likely the hair cell precursors that directly give rise to new hair cells; whereas the anterior-posterior fgfr1a-negative supporting cells have heightened proliferation capacity, likely to serve as more primitive progenitor cells to replenish lost precursors after hair cell loss. Thus fgfr1a is likely to mark compartmentalized supporting cell subtypes with different capacities in renewal proliferation and hair cell regeneration. Manipulation of c-MYC and FGF pathways could be explored for mammalian hair cell regeneration.

  2. Myc and Fgf Are Required for Zebrafish Neuromast Hair Cell Regeneration

    Science.gov (United States)

    Obholzer, Nikolaus D.; Sun, Shan; Li, Wenyan; Petrillo, Marco; Dai, Pu; Zhou, Yi; Cotanche, Douglas A.; Megason, Sean G.; Li, Huawei; Chen, Zheng-Yi

    2016-01-01

    Unlike mammals, the non-mammalian vertebrate inner ear can regenerate the sensory cells, hair cells, either spontaneously or through induction after hair cell loss, leading to hearing recovery. The mechanisms underlying the regeneration are poorly understood. By microarray analysis on a chick model, we show that chick hair cell regeneration involves the activation of proliferation genes and downregulation of differentiation genes. Both MYC and FGF are activated in chick hair cell regeneration. Using a zebrafish lateral line neuromast hair cell regeneration model, we show that the specific inhibition of Myc or Fgf suppresses hair cell regeneration, demonstrating that both pathways are essential to the process. Rapid upregulation of Myc and delayed Fgf activation during regeneration suggest a role of Myc in proliferation and Fgf in differentiation. The dorsal-ventral pattern of fgfr1a in the neuromasts overlaps with the distribution of hair cell precursors. By laser ablation, we show that the fgfr1a-positive supporting cells are likely the hair cell precursors that directly give rise to new hair cells; whereas the anterior-posterior fgfr1a-negative supporting cells have heightened proliferation capacity, likely to serve as more primitive progenitor cells to replenish lost precursors after hair cell loss. Thus fgfr1a is likely to mark compartmentalized supporting cell subtypes with different capacities in renewal proliferation and hair cell regeneration. Manipulation of c-MYC and FGF pathways could be explored for mammalian hair cell regeneration. PMID:27351484

  3. 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.

  4. 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

  5. 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.

  6. 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 ...

  7. 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 ...

  8. 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...

  9. 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...

  10. 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.

  11. Hearing loss and hair cell death in mice given the cholesterol-chelating agent hydroxypropyl-β-cyclodextrin.

    Directory of Open Access Journals (Sweden)

    Mark A Crumling

    Full Text Available Cyclodextrins are sugar compounds that are increasingly finding medicinal uses due to their ability to complex with hydrophobic molecules. One cyclodextrin in particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD, is used as a carrier to solubilize lipophilic drugs and is itself being considered as a therapeutic agent for treatment of Niemann-Pick Type C disease, due to its ability to mobilize cholesterol. Results from toxicological studies suggest that HPβCD is generally safe, but a recent study has found that it causes hearing loss in cats. Whether the hearing loss occurred via death of cochlear hair cells, rendering it permanent, was unexplored. In the present study, we examined peripheral auditory function and cochlear histology in mice after subcutaneous injection of HPβCD to test for hearing loss and correlate any observed auditory deficits with histological findings. On average, auditory brainstem response thresholds were elevated at 4, 16, and 32 kHz in mice one week after treatment with 8,000 mg/kg. In severely affected mice all outer hair cells were missing in the basal half of the cochlea. In many cases, surviving hair cells in the cochlear apex exhibited abnormal punctate distribution of the motor protein prestin, suggesting long term changes to membrane composition and integrity. Mice given a lower dose of 4,000 mg/kg exhibited hearing loss only after repeated doses, but these threshold shifts were temporary. Therefore, cyclodextrin-induced hearing loss was complex, involving cell death and other more subtle influences on cochlear physiology.

  12. The expression of NLRX1 in C57BL/6 mice cochlear hair cells: Possible relation to aging- and neomycin-induced deafness.

    Science.gov (United States)

    Yang, Qianqian; Sun, Gaoying; Cao, Zhixin; Yin, Haiyan; Qi, Qi; Wang, Jinghan; Liu, Wenwen; Bai, Xiaohui; Wang, Haibo; Li, Jianfeng

    2016-03-11

    Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is a cytoplasmic pattern recognition receptor that is predominantly located in mitochondria, which is tightly related to mitochondrial damage, reactive oxygen species (ROS) production, inflammation and apoptosis. The present study was designed to explore whether NLRX1 expresses in C57BL/6 mice cochlear hair cells and, if so, to investigate the possible correlations between NLRX1 and hearing. The location and dynamic expression of NLRX1 were investigated by immunofluorescence, real-time PCR and Western blotting. Hearing thresholds of C57BL/6 mice were measured by auditory brainstem response (ABR). Moreover, the downstream inflammatory and apoptotic pathways regulated by NLRX1 were examined in age-related and neomycin-induced hair cell damage. Data showed that NLRX1 expressed in cytoplasm of C57BL/6 cochlear hair cells, especially in the cilia, which were essential for sound sensation. The expression of NLRX1 in hair cells increased as the mice grew up, and, decreased as they aged. Additionally, the activated apoptotic JNK pathway was detected in 9-month old mice with worse-hearing and 3-month old mice treated with neomycin. Overall, results indicate that NLRX1 may relate to hair cell maturity, hearing formation and maintenance, and promote hair cell apoptosis through JNK pathway induced by aging and neomycin.

  13. 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.

  14. 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

  15. Effects of microbubble size on ultrasound-mediated gene transfection in auditory cells.

    Science.gov (United States)

    Liao, Ai-Ho; Hsieh, Yi-Lei; Ho, Hsin-Chiao; Chen, Hang-Kang; Lin, Yi-Chun; Shih, Cheng-Ping; Chen, Hsin-Chien; Kuo, Chao-Yin; Lu, Ying-Jui; Wang, Chih-Hung

    2014-01-01

    Gene therapy for sensorineural hearing loss has recently been used to insert genes encoding functional proteins to preserve, protect, or even regenerate hair cells in the inner ear. Our previous study demonstrated a microbubble- (MB-)facilitated ultrasound (US) technique for delivering therapeutic medication to the inner ear. The present study investigated whether MB-US techniques help to enhance the efficiency of gene transfection by means of cationic liposomes on HEI-OC1 auditory cells and whether MBs of different sizes affect such efficiency. Our results demonstrated that the size of MBs was proportional to the concentration of albumin or dextrose. At a constant US power density, using 0.66, 1.32, and 2.83 μm albumin-shelled MBs increased the transfection rate as compared to the control by 30.6%, 54.1%, and 84.7%, respectively; likewise, using 1.39, 2.12, and 3.47 μm albumin-dextrose-shelled MBs increased the transfection rates by 15.9%, 34.3%, and 82.7%, respectively. The results indicate that MB-US is an effective technique to facilitate gene transfer on auditory cells in vitro. Such size-dependent MB oscillation behavior in the presence of US plays a role in enhancing gene transfer, and by manipulating the concentration of albumin or dextrose, MBs of different sizes can be produced.

  16. Mast cells as modulators of hair follicle cycling.

    Science.gov (United States)

    Maurer, M; Paus, R; Czarnetzki, B M

    1995-08-01

    While the central role of mast cells (MC) in allergy and inflammation is well-appreciated, much less is known about their physiological functions. The impressive battery of potent growth modulatory MC products, and increasing evidence of MC involvement in hyperproliferative and fibrotic disorders suggest that tissue remodelling may be one of those, namely in the skin. Here, we delineate why this may best be studied by analysing the potential role of MC in hair growth regulation. On the background of numerous, yet widely under-appreciated hints from the older literature, we summarize and discuss our recent observations from the C57BL/6 mouse model for hair research which support the concept that MC are functionally important modulators of hair follicle cycling, specifically during anagen development. This invites to exploit the murine hair cycle as a model for dissecting the physiological growth modulatory functions of MC and encourages the exploration of MC-targeting pharmaceutical strategies for the treatment of hair growth disorders.

  17. [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

  18. 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

  19. Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape.

    Science.gov (United States)

    Etournay, Raphaël; Lepelletier, Léa; Boutet de Monvel, Jacques; Michel, Vincent; Cayet, Nadège; Leibovici, Michel; Weil, Dominique; Foucher, Isabelle; Hardelin, Jean-Pierre; Petit, Christine

    2010-04-01

    Epithelial cells acquire diverse shapes relating to their different functions. This is particularly relevant for the cochlear outer hair cells (OHCs), whose apical and basolateral shapes accommodate the functioning of these cells as mechano-electrical and electromechanical transducers, respectively. We uncovered a circumferential shape transition of the apical junctional complex (AJC) of OHCs, which occurs during the early postnatal period in the mouse, prior to hearing onset. Geometric analysis of the OHC apical circumference using immunostaining of the AJC protein ZO1 and Fourier-interpolated contour detection characterizes this transition as a switch from a rounded-hexagon to a non-convex circumference delineating two lateral lobes at the neural side of the cell, with a negative curvature in between. This shape tightly correlates with the 'V'-configuration of the OHC hair bundle, the apical mechanosensitive organelle that converts sound-evoked vibrations into variations in cell membrane potential. The OHC apical circumference remodeling failed or was incomplete in all the mouse mutants affected in hair bundle morphogenesis that we tested. During the normal shape transition, myosin VIIa and myosin II (A and B isoforms) displayed polarized redistributions into and out of the developing lobes, respectively, while Shroom2 and F-actin transiently accumulated in the lobes. Defects in these redistributions were observed in the mutants, paralleling their apical circumference abnormalities. Our results point to a pivotal role for actomyosin cytoskeleton tensions in the reshaping of the OHC apical circumference. We propose that this remodeling contributes to optimize the mechanical coupling between the basal and apical poles of mature OHCs.

  20. 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

  1. Auditory Neuropathy - A Case of Auditory Neuropathy after Hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Maliheh Mazaher Yazdi

    2007-12-01

    Full Text Available Background and Aim: Auditory neuropathy is an hearing disorder in which peripheral hearing is normal, but the eighth nerve and brainstem are abnormal. By clinical definition, patient with this disorder have normal OAE, but exhibit an absent or severely abnormal ABR. Auditory neuropathy was first reported in the late 1970s as different methods could identify discrepancy between absent ABR and present hearing threshold. Speech understanding difficulties are worse than can be predicted from other tests of hearing function. Auditory neuropathy may also affect vestibular function. Case Report: This article presents electrophysiological and behavioral data from a case of auditory neuropathy in a child with normal hearing after bilirubinemia in a 5 years follow-up. Audiological findings demonstrate remarkable changes after multidisciplinary rehabilitation. Conclusion: auditory neuropathy may involve damage to the inner hair cells-specialized sensory cells in the inner ear that transmit information about sound through the nervous system to the brain. Other causes may include faulty connections between the inner hair cells and the nerve leading from the inner ear to the brain or damage to the nerve itself. People with auditory neuropathy have OAEs response but absent ABR and hearing loss threshold that can be permanent, get worse or get better.

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

    NARCIS (Netherlands)

    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 degen

  3. 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...

  4. 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...

  5. 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

  6. Temporary Neurotrophin Treatment Prevents Deafness-Induced Auditory Nerve Degeneration and Preserves Function

    NARCIS (Netherlands)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B.; Klis, Sjaak F. L.; Grolman, Wilko

    2015-01-01

    After substantial loss of cochlear hair cells, exogenous neurotrophins prevent degeneration of the auditory nerve. Because cochlear implantation, the current therapy for profound sensorineural hearing loss, depends on a functional nerve, application of neurotrophins is being investigated. We address

  7. Electrokinetic shape changes of cochlear outer hair cells

    Science.gov (United States)

    Kachar, Bechara; Brownell, William E.; Altschuler, Richard; Fex, Jörgen

    1986-07-01

    Rapid mechanical changes have been associated with electrical activity in a variety of non-muscle excitable cells1-5. Recently, mechanical changes have been reported in cochlear hair cells6-8. Here we describe electrically evoked mechanical changes in isolated cochlear outer hair cells (OHCs) with characteristics which suggest that direct electrokinetic phenomena are implicated in the response. OHCs make up one of two mechanosensitive hair cell populations in the mammalian cochlea; their role may be to modulate the micromechanical properties of the hearing organ through mechanical feedback mechanisms6-10. In the experiments described here, we applied sinusoidally modulated electrical potentials across isolated OHCs; this produced oscillatory elongation and shortening of the cells and oscillatory displacements of intracellular organdies. The movements were a function of the direction and strength of the electrical field, were inversely related to the ionic concentration of the medium, and occurred in the presence of metabolic uncouplers. The cylindrical shape of the OHCs and the presence of a system of membranes within the cytoplasm-laminated cisternae11-may provide the anatomical substrate for electrokinetic phenomena such as electro-osmosis12,13.

  8. 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

  9. 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

  10. The hair follicle and its stem cells as drug delivery targets.

    Science.gov (United States)

    Hoffman, Robert M

    2006-05-01

    The hair follicle is a skin appendage with a complex structure containing many cell types that produce highly specialised proteins. The hair follicle is in a continuous cycle: anagen is the hair growth phase, catagen the involution phase and telogen is the resting phase. The follicle offers many potential therapeutic targets. Hoffman and colleagues have pioneered hair-follicle-specific targeting using liposomes to deliver small and large molecules, including genes. They have also pioneered ex vivo hair-follicle targeting with continued expression of the introduced gene following transplantation. Recently, it has been discovered that hair follicle stem cells are highly pluripotent and can form neurons, glial cells and other cell types, and this has suggested that hair follicle stem cells may serve as gene therapy targets for regenerative medicine.

  11. 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...

  12. 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.

  13. 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

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

    Science.gov (United States)

    Farahbakhsh, Nasser A; Narins, Peter M

    2008-07-01

    Using video, fluorescence and confocal microscopy, quantitative analysis and modeling, we investigated intracellular processes mediating the calcium/calmodulin (Ca(2+)/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 recorded and compared. These cells respond to ionomycin with a tri-phasic shape change: an initial phase of iso-volumetric length decrease; a period of concurrent shortening and swelling; and the final phase of increase in both length and volume. We found that both the myosin light chain kinase inhibitor, ML-7, and antagonists of the multifunctional Ca(2+)/CaM-dependent kinases, KN-62 and KN-93, inhibit the iso-volumetric shortening phase of the response to ionomycin. The type 1 protein phosphatase inhibitors, calyculin A and okadaic acid induce minor shortening on their own, but do not significantly alter phase 1 response. However, they appear to counter effects of the inhibitors of Ca(2+)/CaM-dependent kinases. We hypothesize that an active actomyosin-based process mediates the iso-volumetric shortening in the frog rostral amphibian papillar hair cells.

  15. 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.

  16. 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...

  17. 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...

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

    Science.gov (United States)

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

    2013-04-01

    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 successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss.

  19. 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

  20. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

    Directory of Open Access Journals (Sweden)

    Peipei Zhang

    2014-10-01

    Full Text Available Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration.

  1. A simplified model of ephitelial cell hair orientation in Drosophila

    Science.gov (United States)

    Garcia-Vergara, Mauricio; Gomez-Correa, Gilberto; Ramirez-Santiago, Guillermo

    2012-02-01

    Epithelia cells are polarized along an axis perpendicular to the apical-basal axis, --``Planar cell polarization'' (PCP)--. In Drosophila adult cuticle cells are hexagonally packed and the PCP gives rise to the elaboration of an actin-rich hair that develops from one of the hexagon vertex and pointing distally. Genetic analyses have identified a group of proteins whose activities are required to polarize each cell and produce the phenomenon of PCP. To describe the PCP in the epithelia some quantitative models intended to explain this phenomenon by invoking diffusion of several proteins and all their interactions. Here we propose a simpler model consisting of two reaction-diffusion equations that describe the redistribution process of two chemical agents inside a cell. This redistribution occurs as a response to an external gradient of a quimio-attractor. We emulate the collective cell polarization by introducing ``interactions'' between neighboring cells that propagate trough the epithelia. This collective polarization gives rise to an orientational pattern in the actin-rich hairs.

  2. 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....

  3. 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.

  4. Local positive feedback regulation determines cell shape in root hair cells.

    Science.gov (United States)

    Takeda, Seiji; Gapper, Catherine; Kaya, Hidetaka; Bell, Elizabeth; Kuchitsu, Kazuyuki; Dolan, Liam

    2008-02-29

    The specification and maintenance of growth sites are tightly regulated during cell morphogenesis in all organisms. ROOT HAIR DEFECTIVE 2 reduced nicotinamide adenine dinucleotide phosphate (RHD2 NADPH) oxidase-derived reactive oxygen species (ROS) stimulate a Ca2+ influx into the cytoplasm that is required for root hair growth in Arabidopsis thaliana. We found that Ca2+, in turn, activated the RHD2 NADPH oxidase to produce ROS at the growing point in the root hair. Together, these components could establish a means of positive feedback regulation that maintains an active growth site in expanding root hair cells. Because the location and stability of growth sites predict the ultimate form of a plant cell, our findings demonstrate how a positive feedback mechanism involving RHD2, ROS, and Ca2+ can determine cell shape.

  5. 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.

  6. 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.

  7. The progenitors of inner ear hair cells and their regulating genes

    Institute of Scientific and Technical Information of China (English)

    SHU Wei-ning; ZHAO Li-dong; ZHANG Xiao-bing; YANG Shi-ming

    2010-01-01

    @@ Hair cells in the mammalian inner ear are very fragile and are often injured as a result of acoustic trauma or exposure to ototoxic drugs (cisplatin, aminoglycosides, etc)[1]. In amphibians and birds, spontaneous post-injury regeneration of all inner ear sensory hair cell occurs, while in the mammalian cochlea, such hearing loss is usually permanent as there are currently no treatments that can lead to post-injury hair cell regeneration.

  8. 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...

  9. The effect of hair bundle shape on hair bundle hydrodynamics of non-mammalian inner ear hair cells for the full frequency range.

    Science.gov (United States)

    Shatz, Lisa F

    2004-09-01

    The effect of the size and the shape of the hair bundle of a hair cell in the inner ear of non-mammals on its motion for the full range of frequencies is determined thereby extending the results of a previous analysis of hair bundle motion for high and low frequencies [Hear Res. 141 (2000) 39-50]. A hemispheroid is used to represent the hair bundle because it can represent a full range of shapes, from thin, pencil-like shapes to wide, flat, disk-like shapes. Boundary element methods are used to approximate the solution for the hydrodynamics. For physiologically relevant parameters, an excellent match is obtained between the model's predictions and measurements of hair bundle motion in the free-standing region of the basilar papilla of the alligator lizard [Aranyosi, Measuring sound-induced motions of the alligator lizard cochlea. Massachusetts Institute of Technology, PhD Thesis, 2002]. Neither in the model's predictions nor in experimental measurements is sharp tuning observed. The model predicted the low frequency region of neural tuning curves for the alligator lizard and bobtail lizard, but could not predict the sharp tuning or the high frequency region. An element that represents an active mechanism is added to the hair bundle model to predict neural tuning curves, which are sharply tuned, and an excellent match is obtained for all the characteristics of neural tuning curves for the alligator lizard, and for the low and high frequency regions for the bobtail lizard. The model does not predict well the sharp tuning of the shorter hair bundles of the bobtail lizard, possibly because it does not represent tectorial sallets.

  10. 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...

  11. A study in motion sickness - Saccular hair cells in the adult bullfrog

    Science.gov (United States)

    Cohen, G. M.; Reschke, M.; Homick, J.

    1982-01-01

    The bullfrog's saccule were examined using light and scanning electron microscopy. No evidence of a striola was found. Type A hair cells were not only distributed peripherally, but also throughout the central macula, though far less frequently than the dominant type D. Two primary hair cell types were distinguished, which corresponded to the ciliary patterns: type A cilia are associated with short, conical hair cells, and type D cilia are associated with long, cylindrical hair cells. Each displays at least one subtype, which may represent developmental precursors. The otolithic membrane is crisscrossed with tunnels and topped with statoconia.

  12. The dynamic range of inner hair cell and organ of Corti responses.

    Science.gov (United States)

    Cheatham, M A; Dallos, P

    2000-03-01

    Inner hair cell (IHC) and organ of Corti (OC) responses are measured from the apical three turns of the guinea pig cochlea, allowing access to regions with best, or most sensitive, frequencies at approximately 250, 1000, and 4000 Hz. In addition to measuring both ac and dc receptor potentials, the average value of the half-wave rectified response (AVEHR) is computed to better reflect the signal that induces transmitter release. This measure facilitates comparisons with single-unit responses in the auditory nerve. Although IHC ac responses exhibit compressive growth, response magnitudes at high levels depend on stimulus frequency. For example, IHCs with moderate and high best frequencies (BF) exhibit more linear responses below the BF of the cell, where higher sound-pressure levels are required to approach saturation. Because a similar frequency dependence is observed in extracellular OC responses, this phenomenon may originate in cochlear mechanics. At the most apical recording location, however, the pattern documented at the base of the cochlea is not seen in IHCs with low BFs around 250 Hz. In fact, more linear behavior is measured above the BF of the cell. These frequency-dependent features require modification of cochlear models that do not provide for longitudinal variations and generally depend on a single stage of saturation located at the synapse. Finally, behavior of dc and AVEHR responses suggests that a single IHC is capable of coding intensity over a large dynamic range [Patuzzi and Sellick, J. Acoust. Soc. Am. 74, 1734-1741 (1983); Smith et al., in Hearing--Physiological Bases and Psychophysics (Springer, Berlin, 1983); Smith, in Auditory Function (Wiley, New York, 1988)] and that information compiled over wide areas along the cochlear partition is not essential for loudness perception, consistent with psychophysical results [Viemeister, Hearing Res. 34, 267-274 (1988)].

  13. 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.

  14. 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

  15. 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 ...

  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. 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...

  18. 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.

  19. Recovery characteristics of the electrically stimulated auditory nerve in deafened guinea pigs : Relation to neuronal status

    NARCIS (Netherlands)

    Ramekers, Dyan; Versnel, Huib; Strahl, Stefan B.; Klis, Sjaak F L; Grolman, Wilko

    2015-01-01

    Successful cochlear implant performance requires adequate responsiveness of the auditory nerve to prolonged pulsatile electrical stimulation. Degeneration of the auditory nerve as a result of severe hair cell loss could considerably compromise this ability. The main objective of this study was to ch

  20. 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

  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. In vitro organotin administration alters guinea pig cochlear outer hair cell shape and viability.

    Science.gov (United States)

    Clerici, W J; Chertoff, M E; Brownell, W E; Fechter, L D

    1993-06-01

    Trimethyltin (TMT) and triethyltin (TET) disrupt auditory function at doses far below those shown to be neurotoxic. In vivo studies suggest that the initial effect of TMT on hearing occurs at the inner hair cell/spiral ganglion cell synapse, while later, the outer hair cell (OHC) undergoes structural and functional damage. TET produces acute effects upon afferent neurotransmission similar to those observed following TMT, but TET's effects on OHC structure and function have not been examined. OHCs are motile elements within the cochlea, believed to modulate the sensitivity and tuning within the inner ear. Changes in OHC length may alter hearing function, and length changes have been reported following exposure to various ototoxic agents in vitro. In the present study, 77 OHCs from 45 pigmented male guinea pigs were isolated in primary culture and exposed for 90 min to concentrations between 30 microM and 1.0 mM of TMT or TET and then to bathing medium for 30 min to remove the toxicant. Significant shortening of the OHC cell body occurred at all doses to both organotins, with a mean reduction in length of 15.1 and 20.2% for 1.0 mM TMT and TET, respectively, at the end of testing; control cells were only 3.4% shorter at the end of 90 min of perfusion with bathing medium. The effect of organotin exposure on OHC volume was not consistently related to either TMT or TET concentration or altered cell length. In addition, disruption of the plasma membrane characterized by bleb formation, the forceful ejection of cytoplasm, or bursting was seen in 80% of cells exposed to 1.0 mM TET, although not TMT; lower concentrations of both organotins disrupted the cell membrane in 10-30% of cells. Membrane rupture was not reliably associated with either increased cell volume or decreased length, implicating a weakening of the plasma membrane or cortical lattice as the basis for this effect. Consistent with the irreversible structural weakening of the lateral wall, resorption of

  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. 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.

  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. 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.

  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. Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla.

    Science.gov (United States)

    Hirvonen, Timo P; Minor, Lloyd B; Hullar, Timothy E; Carey, John P

    2005-02-01

    Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5-25 (early) or 90-115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.

  10. Induction of hair follicle regeneration in rat ear by mi-croencapsulated human hair dermal papilla cells

    Institute of Scientific and Technical Information of China (English)

    LIN Chang-min; LI Yu; JI Ying-chang; HUANG Keng; CAI Xiang-na; LI Guo-qiang

    2009-01-01

    Objective: To induce hair follicle regeneration in rat ear by microencapsulated dermal papillae (DP) cells.Methods: Intact dermal papillae were obtained from human scalp follicles which were digested with collagenase I. The human hair DP cells were encapsulated with alginate-polylysine-alginate (APA) by a high-voltage electric field droplet generator. The diameters of the DP cell microcapsules were optimized by regulating the voltage, the distance be-tween the needle head and the solution surface and the injection speed. Then DP cell microencapsulations were xenotransplanted into ears of 20 SD rats with a novel method. One rat was killed every week at the postoperative 2-12 weeks and the implantation sites were biopsied for histo-logical observation.Results: The DP cell microencapsulations were found in a group of round, smooth and transparent microcapsules under a phase-contrast microscope. The optimal combina-tion of parameters to obtain 0.4 mm DP cell microcapsules was voltage 7.0 kV, injection speed 55 mm/h, and distance 10mm. After 4-12 weeks, 18 of 20 DP cell microcapsule implan-tations had produced high-density hair. Histological obser-vation indicated that both large follicles and sebaceous gland structures were formed in the rat ear within 3-12 weeks.Conclusions: These findings show that the DP cell microencapsulation maintain the capacity for initiating the follicle regeneration and can be considered as a substitute for fresh isolated dermal papillae.

  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. 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.

  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. 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...

  16. 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

    injection. Total volume of the utricle, as well as total number of hair and supporting cells, were estimated on light microscopic sections. Total volume and mean volume of hair cell types I and II and supporting cells were estimated on digital transmission electron micrographs. Total volume of the utricular...... 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...

  17. 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

  18. 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.

  19. 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.

  20. 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 ...

  1. 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...

  2. Lowering extracellular chloride concentration alters outer hair cell shape.

    Science.gov (United States)

    Cecola, R P; Bobbin, R P

    1992-08-01

    In general, increasing external K+ concentration, as well as exposure to hypotonic medium, induces a shortening of outer hair cells (OHCs) accompanied by an increase in width and volume. One possible mechanism suggested for these changes is a movement of Cl- and/or water across the cell membrane. We therefore examined the role of Cl- in OHC volume maintenance by testing the effect of decreasing extracellular Cl- concentration on OHC length and shape. In addition, the effect of hypotonic medium was examined. OHCs were isolated from guinea pig cochleae, mechanically dissociated and dispersed, and placed in a modified Hanks balanced salt solution (HBS). Exposing the cells to a Cl(-)-free HBS produced an initial shortening, which was rapidly followed by an increase in length. After about 9 min of exposure to Cl(-)-free HBS, the cells appeared to lose all water and collapsed. Upon return to normal HBS, the OHCs returned to their normal shape. We speculate that the collapse of the OHCs may be due to the loss of intracellular Cl-, which, in turn, resulted in the loss of intracellular K+ and water. The results indicate that Cl- contributes greatly to the maintenance of OHC volume. In addition, we confirmed that isolated OHCs swell in hypotonic medium and maintain their swollen state until returned to normal medium. The mechanism for maintenance of the swollen state is unknown.

  3. 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...... estimates the total number of utricular hair cells and supporting cells in waltzing guinea pigs and age-matched control animals using the optical fractionator method. Animals were divided into four age groups (1, 7, 49 and 343 day-old). The number of type I hair cells decreased by 20% in the 343 day......-old waltzing guinea pigs compared to age-matched controls and younger animals. Two-photon confocal laser scanning microscopy using antibodies against fimbrin and betaIII-tubulin showed that the rods were exclusive to type I hair cells. There was no significant change in the length of the filament rods with age...

  4. 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.

  5. 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...

  6. 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.

  7. 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].

  8. 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

  9. 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.

  10. Dendritic HCN channels shape excitatory postsynaptic potentials at the inner hair cell afferent synapse in the mammalian cochlea.

    Science.gov (United States)

    Yi, Eunyoung; Roux, Isabelle; Glowatzki, Elisabeth

    2010-05-01

    Synaptic transmission at the inner hair cell (IHC) afferent synapse, the first synapse in the auditory pathway, is specialized for rapid and reliable signaling. Here we investigated the properties of a hyperpolarization-activated current (I(h)), expressed in the afferent dendrite of auditory nerve fibers, and its role in shaping postsynaptic activity. We used whole cell patch-clamp recordings from afferent dendrites directly where they contact the IHC in excised postnatal rat cochlear turns. Excitatory postsynaptic potentials (EPSPs) of variable amplitude (1-35 mV) were found with 10-90% rise times of about 1 ms and time constants of decay of about 5 ms at room temperature. Current-voltage relations recorded in afferent dendrites revealed I(h). The pharmacological profile and reversal potential (-45 mV) indicated that I(h) is mediated by hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels. The HCN channel subunits HCN1, HCN2, and HCN4 were found to be expressed in afferent dendrites using immunolabeling. Raising intracellular cAMP levels sped up the activation kinetics, increased the magnitude of I(h) and shifted the half activation voltage (V(half)) to more positive values (-104 +/- 3 to -91 +/- 2 mV). Blocking I(h) with 50 microM ZD7288 resulted in hyperpolarization of the resting membrane potential (approximately 4 mV) and slowing the decay of the EPSP by 47%, suggesting that I(h) is active at rest and shortens EPSPs, thereby potentially improving rapid and reliable signaling at this first synapse in the auditory pathway.

  11. 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...

  12. Rheotaxis in larval zebrafish is mediated by lateral line mechanosensory hair cells.

    Directory of Open Access Journals (Sweden)

    Arminda Suli

    Full Text Available The lateral line sensory system, found in fish and amphibians, is used in prey detection, predator avoidance and schooling behavior. This system includes cell clusters, called superficial neuromasts, located on the surface of head and trunk of developing larvae. Mechanosensory hair cells in the center of each neuromast respond to disturbances in the water and convey information to the brain via the lateral line ganglia. The convenient location of mechanosensory hair cells on the body surface has made the lateral line a valuable system in which to study hair cell damage and regeneration. One way to measure hair cell survival and recovery is to assay behaviors that depend on their function. We built a system in which orientation against constant water flow, positive rheotaxis, can be quantitatively assessed. We found that zebrafish larvae perform positive rheotaxis and that, similar to adult fish, larvae use both visual and lateral line input to perform this behavior. Disruption or damage of hair cells in the absence of vision leads to a marked decrease in rheotaxis that recovers upon hair cell repair or regeneration.

  13. Sodium and calcium currents shape action potentials in immature mouse inner hair cells.

    Science.gov (United States)

    Marcotti, Walter; Johnson, Stuart L; Rusch, Alfons; Kros, Corne J

    2003-11-01

    Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both alpha1D (Cav1.3) Ca2+ and Na+ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na+ current, and slower, partially Ca2+-dependent inactivation for the Ca2+ current. Only the Ca2+ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na+ current. The Na+ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca2+ current is mainly involved, together with the K+ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca2+ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na+ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na+ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at -71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.

  14. 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 ...

  15. 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...

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. 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...

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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 ...

  14. 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.

  15. 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

  16. 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.

  17. 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 ...

  18. 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.

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

    Science.gov (United States)

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

    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 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.

  20. 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...

  1. Cotransfection of Pax2 and Math1 promote in situ cochlear hair cell regeneration after neomycin insult.

    Science.gov (United States)

    Chen, Yan; Yu, Huiqian; Zhang, Yanping; Li, Wen; Lu, Na; Ni, Wenli; He, Yingzi; Li, Jin; Sun, Shan; Wang, Zhengmin; Li, Huawei

    2013-10-21

    The ideal strategy for hair cell regeneration is promoting residual supporting cell proliferation followed by induction of hair cell differentiation. In this study, cultured neonatal mouse organs of Corti were treated with neomycin to eliminate hair cells followed by incubation with recombined adenovirus expressing Pax2 and/or Math1. Results showed that overexpression of Pax2 significantly promoted proliferation of supporting cells. The number of BrdU⁺/myosin VIIA⁺ cells increased significantly in hair cell pre-existing region two weeks after adenovirus infection in Ad-Pax2-IRES-Math1 group compared to Ad-Pax2 and Ad-Math1 groups. This indicated that cotransfection of Pax2 and Math1 induced supporting cells to proliferate and differentiate into hair cells in situ. Most new hair cells were labeled by FM1-43 suggesting they acquired certain function. The results also suggest that inducing proliferating cells rather than quiescent cells to differentiate into hair cells by forced expression of Math1 is feasible for mammalian hair cell regeneration.

  2. 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...

  3. Mechanoelectrical Transducer Has Discrete Conductances in the Chick Vestibular Hair Cell

    Science.gov (United States)

    Ohmori, Harunori

    1984-03-01

    Properties of mechanoelectrical transduction were studied at the single-cell level by applying a whole-cell recording variation of the patch-clamp technique to dissociated vestibular hair cells of chicks. The hair bundle was directly stimulated by a glass rod, and transduction currents were recorded from the cell body. After a triangular movement of the stimulating probe, the transduction current was generated stepwise between discrete levels of amplitude. The minimum step amplitude was -1.8 pA at -27 mV in Na-containing normal saline.

  4. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge.

    Science.gov (United States)

    Liu, Yaping; Lyle, Stephen; Yang, Zaixin; Cotsarelis, George

    2003-11-01

    Putative epithelial stem cells in the hair follicle bulge are thought to play pivotal roles in the homeostasis, aging, and carcinogenesis of the cutaneous epithelium. Elucidating the role of bulge cells in these processes has been hampered by the lack of gene promoters that target this area with specificity. Here we describe the isolation of the mouse keratin 15 (K15) promoter and demonstrate its utility for preferentially targeting hair follicle bulge cells in adult K15/lacZ transgenic mice. We found that patterns of K15 expression and promoter activity changed with age and correlated with levels of differentiation within the cutaneous epithelium; less differentiated keratinocytes in the epidermis of the neonatal mouse and in the bulge area of the adult mouse preferentially expressed K15. These findings demonstrate the utility of the K15 promoter for targeting epithelial stem cells in the hair follicle bulge and set the stage for elucidating the role of bulge cells in skin biology.

  5. An Auditory Model of Improved Adaptive ZCPA

    Directory of Open Access Journals (Sweden)

    Jinping Zhang

    2013-07-01

    Full Text Available An improved ZCAP auditory model with adaptability is proposed in this paper, and the  adaptive method designed for ZCPA model is suitable for other auditory model with inner-hair-cell sub-model. The first step in the implement process of the proposed ZCPA model is to carry out the calculation of inner product between signal and complex Gammatone filters to obtain important frequency components  of signal. And then, according to  the result of the first step, the parameters of the basilar membrane sub-model and frequency box are automatically adjusted, such as the number of the basilar membrane filters, center frequency and bandwith of each basilar membrane filter, position of each frequency box, and so on. Lastly  an auditory model is built, and the final output is auditory spectrum.The results of numerical simulation and experiments have showed that the proposed model could realize accurate frequency selection, and the auditory spectrum is more distinctly than that of conventional ZCPA model. Moreover, the proposed model can completely avoided the influence of the number of filter on the shape of auditory spectrum existing in conventional ZCPA model so that the shape of auditory spectrum is steady, and the data quantity is small.

  6. 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.

  7. Frequency response for electromotility of isolated outer hair cells of the guinea pig

    NARCIS (Netherlands)

    Wit, HP; vanDijk, P; Segenhout, HM

    1996-01-01

    Frequency and impulse responses were determined for isolated guinea pig outer hair cells by electrically stimulating the cells between two wire electrodes with white noise. Cells were attached to the bottom of a small culture dish at one end while the other end was freely moving. Results have the ch

  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. 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...

  10. 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.

  11. Effects of salicylate on sound-evoked outer hair cell stereocilia deflections.

    Science.gov (United States)

    Hakizimana, Pierre; Fridberger, Anders

    2015-09-01

    Hearing depends on sound-evoked deflections of the stereocilia that protrude from the sensory hair cells in the inner ear. Although sound provides an important force driving stereocilia, forces generated through mechanically sensitive ion channels and through the motor protein prestin have been shown to influence stereocilia motion in solitary hair cells. While a possible influence of prestin on mechanically sensitive ion channels has not been systematically investigated, a decrease in transducer currents is evident in solitary hair cells when prestin is blocked with salicylate, raising the question of whether a reduced prestin activity or salicylate itself affected the mechanotransduction apparatus. We used two- and three-dimensional time-resolved confocal imaging to visualize outer hair cell stereocilia during sound stimulation in the apical turn of cochlear explant preparations from the guinea pig. Surprisingly, following application of salicylate, outer hair cell stereocilia deflections increased, while cochlear microphonic potentials decreased. However, when prestin activity was altered with the chloride ionophore tributyltin, both the cochlear microphonic potential and the stereocilia deflection amplitude decreased. Neither positive nor negative current stimulation abolished the bundle movements in the presence of salicylate, indicating that the observed effects did not depend on the endocochlear potential. These data suggest that salicylate may alter the mechanical properties of stereocilia, decreasing their bending stiffness.

  12. Rat hair follicle stem cells differentiate and promote recovery following spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Nowruz Najafzadeh; Maliheh Nobakht; Bagher Pourheydar; Mohammad Ghasem Golmohammadi

    2013-01-01

    Emerging studies of treating spinal cord injury (SCI) with adult stem cells led us to evaluate the effects of transplantation of hair fol icle stem cells in rats with a compression-induced spinal cord lesion. Here, we proposed a hypothesis that rat hair fol icle stem celltransplantation can promote the recovery of injured spinal cord. Compression-induced spinal cord injury was induced in Wistar rats in this study. The bulge area of the rat vibrissa fol icles was isolated, cultivated and characterized with nestin as a stem cellmarker. 5-Bromo-2′-deoxyuridine (BrdU) labeled bulge stem cells were transplanted into rats with spinal cord injury. Immunohistochemical staining results showed that some of the grafted cells could survive and differentiate into oligodendrocytes (receptor-interacting protein positive cells) and neuronal-like cells (βIII-tubulin positive cells) at 3 weeks after transplantation. In addition, recovery of hind limb locomotor function in spinal cord injury rats at 8 weeks fol owing celltransplantation was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The results demon-strate that the grafted hair fol icle stem cells can survive for a long time period in vivo and differentiate into neuronal- and glial-like cells. These results suggest that hair fol icle stem cells can promote the recovery of spinal cord injury.

  13. 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

  14. Noise-induced cell death in the mouse medial geniculate body and primary auditory cortex.

    Science.gov (United States)

    Basta, Dietmar; Tzschentke, Barbara; Ernst, Arne

    Noise-induced effects within the inner ear have been well investigated for several years. However, this peripheral damage cannot fully explain the audiological symptoms in noise-induced hearing loss (NIHL), e.g. tinnitus, recruitment, reduced speech intelligibility, hyperacusis. There are few reports on central noise effects. Noise can induce an apoptosis of neuronal tissue within the lower auditory pathway. Higher auditory structures (e.g. medial geniculate body, auditory cortex) are characterized by metabolic changes after noise exposure. However, little is known about the microstructural changes of the higher auditory pathway after noise exposure. The present paper was therefore aimed at investigating the cell density in the medial geniculate body (MGB) and the primary auditory cortex (AI) after noise exposure. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun, 10:1). After 1 week, auditory brainstem response recordings (ABR) were performed in noise exposed and normal hearing animals. After fixation, the brain was microdissected and stained (Kluever-Barrera). The cell density in the MGB subdivisions and the AI were determined by counting the cells within a grid. Noise-exposed animals showed a significant ABR threshold shift over the whole frequency range. Cell density was significantly reduced in all subdivisions of the MGB and in layers IV-VI of AI. The present findings demonstrate a significant noise-induced change of the neuronal cytoarchitecture in central key areas of auditory processing. These changes could contribute to the complex psychoacoustic symptoms after NIHL.

  15. 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.

  16. [Hair and their environment].

    Science.gov (United States)

    Piérard-Franchimont, C; Piérard, G E

    2015-02-01

    Hair is influenced by the effects of the daily environment. Some toxic xenobiotics slow down or block the cell renewal of the hair matrix, thus inhibiting hair growth. The ultraviolet light obviously influences the physical structure and physiology of the hair follicle. Tobacco is similarly responsible for negative influences on the evolution of various alopecias. Several cosmetic procedures for maintaining and making hair more attractive are not always harmless, and they occasionally represent a possible origin for alopecia. PMID:26011990

  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. Suprathreshold Stochastic Resonance in Mechanoelectrical Transduction of Hair Cells

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xiang-Hui; LONG Zhang-Cai; ZHANG Bing; YANG Nan

    2008-01-01

    @@ Haircell, the sound signal sensor in the auditory system, works in an environment full of noise. This noise has been demonstrated before to be a factor beneficial to the transfer of subthreshold weak signal. We further theoretically demonstrate that in suprathreshold signal situation, noise can still be a beneficial factor and enhance the halrcell nonlinear transfer of suprathreshold signal. This reveals an additional constructive function of noise in hearing and provides theoretic foundation for relevant applications.

  19. In Vivo Cochlear Hair Cell Generation and Survival by Coactivation of β-Catenin and Atoh1

    Science.gov (United States)

    Kuo, Bryan R.; Baldwin, Emily M.; Layman, Wanda S.; Taketo, Makoto Mark

    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 cochlea than previously reported, most of which survive to adulthood. We achieved this by combining the expression of a constitutively active form of β-catenin (a canonical Wnt activator) with ectopic expression of Atoh1 (a HC fate determination factor) in neonatal Lgr5+ cells (the presumed SC and HC progenitors of the postnatal mouse cochlea), and discovered synergistic increases in proliferation and differentiation. The new HCs were predominantly located near the endogenous inner HCs, expressed early HC differentiation markers, and were innervated despite incomplete alignment of presynaptic and postsynaptic markers. Surprisingly, genetic tracing revealed that only a subset of Lgr5+ cells that lie medial to the inner HCs respond to this combination, highlighting a previously unknown heterogeneity that exists among Lgr5+ cells. Together, our data indicate that β-catenin and Atoh1 mediate synergistic effects on both proliferation and differentiation of a subset of neonatal cochlear Lgr5+ cells, thus overcoming major limitations of HC regeneration in postnatal mouse cochleae in vivo. These results provide a basis for combinatorial therapeutics for hearing restoration. SIGNIFICANCE STATEMENT Hearing loss in humans from aging, noise exposure, or ototoxic drugs (i.e., cisplatin or some antibiotics) is permanent and affects every segments of the population, worldwide. However, birds, frog, and fish have the ability to recover hearing, and recent studies have focused on understanding

  20. A hardware model of the auditory periphery to transduce acoustic signals into neural activity

    Directory of Open Access Journals (Sweden)

    Takashi eTateno

    2013-11-01

    Full Text Available To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.

  1. 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...

  2. 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/...

  3. 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

  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. Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair.

    Directory of Open Access Journals (Sweden)

    Keigo Yoshizaki

    Full Text Available Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1, is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1 dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2 Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3 epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.

  6. Analogues of simple and complex cells in rhesus monkey auditory cortex.

    Science.gov (United States)

    Tian, Biao; Kuśmierek, Paweł; Rauschecker, Josef P

    2013-05-01

    Receptive fields (RFs) of neurons in primary visual cortex have traditionally been subdivided into two major classes: "simple" and "complex" cells. Simple cells were originally defined by the existence of segregated subregions within their RF that respond to either the on- or offset of a light bar and by spatial summation within each of these regions, whereas complex cells had ON and OFF regions that were coextensive in space [Hubel DH, et al. (1962) J Physiol 160:106-154]. Although other definitions based on the linearity of response modulation have been proposed later [Movshon JA, et al. (1978) J Physiol 283:53-77; Skottun BC, et al. (1991) Vision Res 31(7-8):1079-1086], the segregation of ON and OFF subregions has remained an important criterion for the distinction between simple and complex cells. Here we report that response profiles of neurons in primary auditory cortex of monkeys show a similar distinction: one group of cells has segregated ON and OFF subregions in frequency space; and another group shows ON and OFF responses within largely overlapping response profiles. This observation is intriguing for two reasons: (i) spectrotemporal dissociation in the auditory domain provides a basic neural mechanism for the segregation of sounds, a fundamental prerequisite for auditory figure-ground discrimination; and (ii) the existence of similar types of RF organization in visual and auditory cortex would support the existence of a common canonical processing algorithm within cortical columns.

  7. Auditory model inversion and its application

    Institute of Scientific and Technical Information of China (English)

    ZHAO Heming; WANG Yongqi; CHEN Xueqin

    2005-01-01

    Auditory model has been applied to several aspects of speech signal processing field, and appears to be effective in performance. This paper presents the inverse transform of each stage of one widely used auditory model. First of all it is necessary to invert correlogram and reconstruct phase information by repetitious iterations in order to get auditory-nerve firing rate. The next step is to obtain the negative parts of the signal via the reverse process of the HWR (Half Wave Rectification). Finally the functions of inner hair cell/synapse model and Gammatone filters have to be inverted. Thus the whole auditory model inversion has been achieved. An application of noisy speech enhancement based on auditory model inversion algorithm is proposed. Many experiments show that this method is effective in reducing noise.Especially when SNR of noisy speech is low it is more effective than other methods. Thus this auditory model inversion method given in this paper is applicable to speech enhancement field.

  8. The effect of quinine on outer hair cell shape, compliance and force.

    Science.gov (United States)

    Jarboe, J K; Hallworth, R

    1999-06-01

    Quinine intoxication causes a well-described syndrome that includes tinnitus, sensorineural hearing loss and vertigo. The pathophysiology of quinine's effects on hearing is unknown, but may include a peripheral component. The cochlear outer hair cell is known to be motile and to contribute force to amplify the vibration pattern of the organ of Corti. The outer hair cell is also a target of diseases involving tinnitus and sensorineural hearing loss, including salicylate intoxication. These effects may be mediated through changes either in motile force or in mechanical properties. Quinine's effects on outer hair cell motility and mechanical properties have therefore been examined in vitro. Quinine at 5.0 mM substantially decreased active force generation in isolated guinea pig cochlear outer hair cells. Isolated cells also elongated and dilated in diameter when exposed to 5.0 mM quinine. No consistent changes in mechanical properties were observed. 1.0 mM quinine was ineffective in either force reduction or elongation. Trifluoperazine, a calmodulin inhibitor, and ML-9, a blocker of myosin light chain kinases, were ineffective in blocking quinine-induced force reduction or elongation. Deferoxamine, a hydroxyl free radical scavenger, also failed to block either the force decrease or the elongation.

  9. 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.

  10. 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.

  11. Hair cosmetics and camouflage technics

    Directory of Open Access Journals (Sweden)

    Zahide Eriş Eken

    2014-06-01

    Full Text Available 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, hair protective products, camouflage products are most commonly used hair cosmetics. Hair shaping procedures are frequently applied.

  12. The delayed rectifier, IKI, is the major conductance in type I vestibular hair cells across vestibular end organs

    Science.gov (United States)

    Ricci, A. J.; Rennie, K. J.; Correia, M. J.

    1996-01-01

    Hair cells were dissociated from the semicircular canal, utricle, lagena and saccule of white king pigeons. Type I hair cells were identified morphologically based on the ratios of neck width to cuticular plate width (NPR technique was used to measure electrical properties from type I hair cells. In voltage-clamp, the membrane properties of all identified type I cells were dominated by a predominantly outward potassium current, previously characterized in semicircular canal as IKI. Zero-current potential, activation, deactivation, slope conductance, pharmacologic and steady-state properties of the complex currents were not statistically different between type I hair cells of different vestibular end organs. The voltage dependence causes a significant proportion of this conductance to be active about the cell's zero-current potential. The first report of the whole-cell activation kinetics of the conductance is presented, showing a voltage dependence that could be best fit by an equation for a single exponential. Results presented here are the first data from pigeon dissociated type I hair cells from utricle, saccule and lagena suggesting that the basolateral conductances of a morphologically identified population of type I hair cells are conserved between functionally different vestibular end organs; the major conductance being a delayed rectifier characterized previously in semicircular canal hair cells as IKI.

  13. 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...

  14. 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

  15. Role for a novel Usher protein complex in hair cell synaptic maturation.

    Directory of Open Access Journals (Sweden)

    Marisa Zallocchi

    Full Text Available The molecular mechanisms underlying hair cell synaptic maturation are not well understood. Cadherin-23 (CDH23, protocadherin-15 (PCDH15 and the very large G-protein coupled receptor 1 (VLGR1 have been implicated in the development of cochlear hair cell stereocilia, while clarin-1 has been suggested to also play a role in synaptogenesis. Mutations in CDH23, PCDH15, VLGR1 and clarin-1 cause Usher syndrome, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa. Here we show developmental expression of these Usher proteins in afferent spiral ganglion neurons and hair cell synapses. We identify a novel synaptic Usher complex comprised of clarin-1 and specific isoforms of CDH23, PCDH15 and VLGR1. To establish the in vivo relevance of this complex, we performed morphological and quantitative analysis of the neuronal fibers and their synapses in the Clrn1-/- mouse, which was generated by incomplete deletion of the gene. These mice showed a delay in neuronal/synaptic maturation by both immunostaining and electron microscopy. Analysis of the ribbon synapses in Ames waltzer(av3J mice also suggests a delay in hair cell synaptogenesis. Collectively, these results show that, in addition to the well documented role for Usher proteins in stereocilia development, Usher protein complexes comprised of specific protein isoforms likely function in synaptic maturation as well.

  16. 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.

  17. 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.

  18. 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

    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...

  19. 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...

  20. Anaesthetics may change the shape of isolated type I hair cells.

    Science.gov (United States)

    Scarfone, E; Ulfendahl, M; Figueroa, L; Flock, A

    1991-08-01

    Type I hair cells isolated from animals anaesthetised with barbiturates or ether were found to be shorter and to lack a prominent 'neck' region when compared to cells isolated from non-anaesthetised animals. Ketamine did not have this effect. The changes observed could have important implications for the physiology of inner ear receptors. These findings infer that care should be taken in the choice of anaesthetics used in studies on cells from the inner ear.

  1. 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.

  2. Nature of the motor element in electrokinetic shape changes of cochlear outer hair cells.

    Science.gov (United States)

    Dallos, P; Evans, B N; Hallworth, R

    1991-03-14

    It is the prevailing notion that cochlear outer hair cells function as mechanical effectors as well as sensory receptors. Electrically induced changes in the shape of mammalian outer hair cells, studied in vitro, are commonly assumed to represent an aspect of their effector process that may occur in vivo. The nature of the motile process is obscure, even though none of the established cellular motors can be involved. Although it is known that the motile response is under voltage control, it is uncertain whether the stimulus is a drop in the voltage along the long axis of the cell or variation in the transmembrane potential. We have now performed experiments with cells partitioned in differing degrees between two chambers. Applied voltage stimulates the cell membrane segments in opposite polarity to an amount dependent on the partitioning. The findings show, in accordance with previous suggestions, that the driving stimulus is a local transmembrane voltage drop and that the cellular motor consists of many independent elements, distributed along the cell membrane and its associated cortical structures. We further show that the primary action of the motor elements is along the longitudinal dimension of the cell without necessarily involving changes in intracellular hydrostatic pressure. This establishes the outer hair cell motor as unique among mechanisms that control cell shape.

  3. 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.

  4. 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.

  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. The cuticular plate: a riddle, wrapped in a mystery, inside a hair cell.

    Science.gov (United States)

    Pollock, Lana M; McDermott, Brian M

    2015-06-01

    The mechanosensitive hair cells of the inner ear are crucial to hearing and vestibular function. Each hair cell detects the mechanical stimuli associated with sound or head movement with a hair bundle at the apical surface of the cell, consisting of a precise array of actin-based stereocilia. Each stereocilium inserts as a rootlet into a dense filamentous actin mesh known as the cuticular plate. Disruption of the parallel actin bundles forming the stereocilia results in hearing impairments and balance defects. The cuticular plate is thought to be involved in holding the stereocilia in place. However, the precise role of the cuticular plate in hair bundle development, maintenance, and hearing remains unknown. Ultrastructural studies have revealed a complex cytoskeletal architecture, but a lack of knowledge of proteins that inhabit the cuticular plate and a dearth of mutations that perturb relevant proteins have hindered our understanding of the functions of the cuticular plate. Here, we discuss what is known about the structure and development of this unique and poorly-understood actin-rich organelle. PMID:26104653

  7. Shape changes in isolated outer hair cells: measurements with attached microspheres.

    Science.gov (United States)

    Zajic, G; Schacht, J

    1991-04-01

    Shape changes can be induced in isolated outer hair cells by various stimuli and quantified from digitized video-images. While overall changes in length between base and apex are easily measured, changes in defined segments of the cell require fixed landmarks on the cell body. The problem of locating such landmarks makes it difficult to assess if a change in length is uniform or largely confined to a particular segment of the cell. This information is important in identifying the location of a contractile apparatus and the elucidation of mechanisms of motility. We demonstrate here that microspheres can serve as reference points for such measurements. By attaching microspheres to cells we determined that, when outer hair cells increased their volume upon K(+)-depolarization, their middle segment shortened more significantly (14 +/- 6%) than either the basal (10 +/- 5%) or apical section (7 +/- 6%; P less than 0.01). In contrast, when cortical contractions were induced by elevating intracellular Ca2+, the elongation of the cells was more pronounced in their basal (8 +/- 2%) than their apical (6 +/- 2%; P = 0.06) or middle region (6 +/- 3%). This study provides further insight into the mechanisms of shape changes in isolated outer hair cells and illustrates a method to analyze localized changes in the absence of internal landmarks.

  8. Glutaraldehyde induces cell shape changes in isolated outer hair cells from the inner ear.

    Science.gov (United States)

    Slepecky, N; Ulfendahl, M

    1988-01-01

    Individual isolated outer hair cells (OHCs) from the cochlea were maintained in a collagen gel and viewed in the light microscope. They were observed during fixation and processing for transmission electron microscopy and individual cells were selected for observation in the electron microscope. Application of glutaraldehyde at several concentrations caused OHCs to become shorter. Shrinkage occurred during dehydration but there was no further change during infiltration with the epoxy resin. Ultrastructural analysis of isolated cells fixed with glutaraldehyde and postfixed with osmium tetroxide showed that these cells were similar to cells fixed in the intact cochlea. The glutaraldehyde-induced cell shape change is similar to the shortening seen in intact OHCs in response to the application of solutions containing high potassium or caffeine. Application of glutaraldehyde to cells pretreated with potassium or caffeine caused further shortening. Glutaraldehyde-induced cell shape change was not blocked by the application of tetracaine, which did prevent potassium-induced and caffeine-induced shortening. Glutaraldehyde-induced cell shape change was not stopped by short treatment with N-ethylmaleimide, which did inhibit potassium-induced shortening. Results from these experiments suggest that the glutaraldehyde-induced OHC shape change is not caused by an effect on the membrane or by calcium activation of a contractile response. Shortening may be caused by shrinkage due to cross-linking of proteins.

  9. A cytoskeletal spring for the control of cell shape in outer hair cells isolated from the guinea pig cochlea.

    Science.gov (United States)

    Holley, M C; Ashmore, J F

    1990-01-01

    A two-dimensional cortical cytoskeletal lattice associated with the lateral plasma membranes of mammalian outer hair cells maintains cell shape and provides a restoring force to oppose active changes in cell length. The lattice is composed of two morphologically distinct filaments which are arranged to reinforce the cell circumferentially whilst allowing limited changes in cell length and diameter. This function can only be fulfilled if intracellular pressure is high enough to put the lattice under tension.

  10. 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...

  11. 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.

  12. 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

  13. 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...

  14. 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 ...

  15. 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

  16. Protective role of NecroX-5 against neomycin-induced hair cell damage in zebrafish.

    Science.gov (United States)

    Song, Jae-Jun; Chang, Jiwon; Choi, Jungim; Im, Gi Jung; Chae, Sung Won; Lee, Seung Hoon; Kwon, Soon-Young; Jung, Hak Hyun; Chung, Ah-Young; Park, Hae-Chul; Choi, June

    2014-02-01

    NecroX-5, one of the derivatives of NecroX series compounds, is a mitochondrial reactive oxygen species and reactive nitrogen species scavenger that inhibits cell death against various kinds of oxidative stresses. The objective of the present study was to evaluate the effects of NecroX-5 on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Five days post-fertilization, zebrafish larvae were exposed to 125 μM neomycin and one of the following NecroX-5 concentrations for 1 h: 10, 25, 50, and 75 μM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy (n = 10). The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and 2-[4-(dimethylamino) styryl]-N-ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis and mitochondrial damage. Ultrastructural changes were evaluated using scanning electron microscopy. NecroX-5 decreased neomycin-induced hair cell loss in the neuromasts (NecroX-5 50 μM: 13.4 ± 2.0 cells, 125 μM neomycin only: 8.1 ± 1.2 cells; n = 10, P neomycin and 50 μM NecroX-5. NecroX-5 decreased apoptosis and mitochondrial damage. In conclusion, NecroX-5 attenuated neomycin-induced hair cell loss in zebrafish.

  17. Relationship between stiffness, internal cell pressure and shape of outer hair cells isolated from the guinea-pig hearing organ.

    Science.gov (United States)

    Chan, E; Ulfendahl, M

    1997-12-01

    The mechanical properties of outer hair cells are of importance for normal hearing, and it has been shown that damage of the cells can lead to a reduction in the hearing sensitivity. In this study, we measured the stiffness of isolated outer hair cells in hyper- and hypotonic conditions, and examined the change in stiffness in relation to the corresponding changes in internal cell pressure and cell shape. The results showed that the axial stiffness of isolated outer hair cells (30-90 microns in length, 8-12 microns in diameter), ranging from 0.13-5.39 mN m-1, was inversely related to cell length. Exposure to hyper- and hypotonic external media with a small percentage change in osmolality caused a similar magnitude of change in cell length and cell diameter, but an average 60% change in cell stiffness. Therefore, a moderate osmotic change in the external medium can lead to a significant alteration in cell stiffness. The findings thus indicate an important contribution of internal cell pressure to cell stiffness.

  18. 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...

  19. 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...

  20. 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.

  1. 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

  2. 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

  3. 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.

  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. 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

  6. 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.

  7. A Hair-cell Structure based Piezoelectric Energy Harvester Operating under Three Dimensional Arbitrary Vibrations

    Science.gov (United States)

    Park, H.; Na, Y.; Park, J.; Park, J. Y.

    2013-12-01

    A hair-cell structure based piezoelectric energy harvester was newly developed to effectively scavenge three-dimensional vibrations. The cantilever of the proposed energy harvester, called a hair-cell structure, is deliberately elongated and curled so that it oscillates with decent displacement under not only vertically induced vibrations, but also under longitudinally and horizontally induced vibrations. The proposed energy harvester is comprised of an elongated and curled piezoelectric cantilever and a proof mass with high aspect ratio at the free end of the cantilever. The fabricated device generated the peak output voltage of 15 mV under vertically induced vibrations with an acceleration of 50 m/s2 at its resonance frequency of 116 Hz. Furthermore, it also generated the peak output voltage of 33 mV and 10 mV under longitudinally and horizontally induced vibrations, respectively.

  8. 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 ...

  9. Sodium Selenite Acts as an Otoprotectant against Neomycin-Induced Hair Cell Damage in a Zebrafish Model.

    Science.gov (United States)

    Chang, Jiwon; Choi, June; Rah, Yoon Chan; Yoo, Myung Hoon; Oh, Kyoung Ho; Im, Gi Jung; Lee, Seung Hoon; Kwon, Soon Young; Park, Hae-Chul; Chae, Sung Won; Jung, Hak Hyun

    2016-01-01

    Sodium selenite is a trace element essential for many physiological functions in the body. It is involved in various biological processes; it acts as a cofactor for antioxidant enzymes that protect against free radicals and is reported to limit metal-mediated oxidative DNA damage. In the present study, we investigated the effect of sodium selenite on neomycin ototoxicity in wild-type and transgenic zebrafish (Brn3C: EGFP). Five or six days post-fertilization, zebrafish larvae were co-exposed to 125 μM neomycin and various concentrations (10 μM, 100 μM, 250 μM, and 500 μM) of sodium selenite for 1 h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy (n = 10 fish per treatment). Hair cell survival was estimated as the ratio of the hair cell numbers in each group compared to those of the control group that were not exposed to neomycin. Apoptosis and hair cell damage of neuromasts were evaluated using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay and 2-[4-(dimethylamino) styryl]-N-ethylpyridinium iodide (DASPEI) assay, respectively. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy. Neuromast hair cells were preserved in zebrafish exposed to 125 μM neomycin and 500 μM sodium selenite for 1 h. Sodium selenite protected against neomycin-induced hair cell loss of neuromasts, reduced apoptosis, and prevented zebrafish ultrastructural changes. We propose that sodium selenite protects against neomycin-induced hair cell damage by inhibiting apoptosis, decreasing the disarray of stereocilia, and preventing ultrastructural changes in the neuromast hair cells of the zebrafish.

  10. 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...

  11. 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...

  12. 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 ...

  13. 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 ...

  14. 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....

  15. 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...

  16. 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...

  17. 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...

  18. Acute Stress-Induced Changes in Follicular Dermal Papilla Cells and Mobilization of Mast Cells: Implications for Hair Growth

    Science.gov (United States)

    Shin, Hyoseung; Choi, Soon-Jin; Cho, A-Ri; Kim, Dong Young; Kim, Kyu Han

    2016-01-01

    Background Stress is a known cause of hair loss in many species. Objective In this study, we investigated the role of acute stress on hair growth using a rat model. Methods Rats were immobilized for 24 hours and blood samples, and skin biopsies were taken. The effect of stress-serum on the in vitro proliferation of rat and human dermal papilla cells (hDPCs), as well as serum cortisol and corticotropin-releasing hormone levels, were measured. Mast cell staining was performed on the biopsied tissue. In addition, Western blot and quantitative real time polymerase chain reaction were used to assess mast cell tryptase and cytokine expression, respectively in rat skin biopsies. Results Stress-serum treatment reduced significantly the number of viable hDPCs and arrested the cell cycle in the G1 phase, compared to serum from unrestrained rats (phair growth via cortisol release in addition to substance P-mast cell pathway.

  19. 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.

  20. Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice.

    Science.gov (United States)

    Hu, J; Xu, M; Yuan, J; Li, B; Entenman, S; Yu, H; Zheng, Q Y

    2016-03-01

    Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cadherin23 (Cdh23) gene, Cdh23(erl/erl), was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23(erl/erl) mice (erl mice), this study investigated TUDCA's otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12.

  1. 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.

  2. Stiffness changes of the cupula associated with the mechanics of hair cells in the fish lateral line.

    Science.gov (United States)

    van Netten, S M; Khanna, S M

    1994-02-15

    Cupular vibration in the lateral-line canal of fish was measured in response to motion of the fluid in the canal by laser-heterodyne interferometry. The results show that the mechanical output/input ratio of the cupula depends on the stimulus amplitude; the cupula thus behaves nonlinearly. The nonlinearity is due to the hair bundles, since it disappears when the cupula is uncoupled from the underlying hair cells. A model of cupular dynamics in which the behavior of the gating springs of the hair cells is incorporated predicts nonlinear responses that are similar to the measurements, suggesting that the nonlinear behavior of the cupula may be attributed to the opening and closing of the transduction channels of the hair cells.

  3. Interaction of minoxidil with pigment in cells of the hair follicle: an example of binding without apparent biological effects.

    Science.gov (United States)

    Buhl, A E; Kawabe, T T; MacCallum, D K; Waldon, D J; Knight, K A; Johnson, G A

    1992-01-01

    To identify minoxidil target cells in hair follicles we followed the uptake of radiolabeled drug in mouse vibrissae follicles both in vitro and in vivo. Autoradiography showed that both 3H-minoxidil and 3H-minoxidil sulfate accumulated in the differentiating epithelial matrix cells superior to the dermal papilla, a distribution similar to that of pigment. Minoxidil localized in melanocytes, melanocyte processes, and areas of greater melanin concentrations within the epithelial cells. Although uptake of minoxidil was significantly less in unpigmented follicles, the drug stimulated proliferation and differentiation of both pigmented and unpigmented follicles. Labeled minoxidil bound to Sepia melanin and was displaced with unlabeled minoxidil and other electron donor drugs. This interaction with melanin acts as a targeting mechanism of minoxidil to pigmented hair follicles but has no apparent functional significance in hair growth. This work illustrates how measurement of drugs in hair may be biased by pigmentation.

  4. Future application of hair follicle stem cells: capable in differentiation into sweat gland cells

    Institute of Scientific and Technical Information of China (English)

    WANG Yao; LIU Zhi-yue; ZHAO Qing; SUN Tong-zhu; MA Kui; FU Xiao-bing

    2013-01-01

    Background Sweat glands (SGs) can not regenerate after complete destruction in the severe skin injury,so it is important to find a ideal stem cell source in order to regenerate functional SGs.Hair follicle stem cells (HFSCs)possess the obvious properties of the adult stem cells,which are multipotent and easily accessible.In this research,we attempted to direct the HFSCs suffered from the sweat gland cells (SGCs) special differentiation by a cooperative coculture system in vitro.Methods The designed co-culture microenvironment in the transwell was consist of two critial factors:heat shocked SGCs and dermis-like mesenchymal tissue,which appeared independently in the two control groups; after induction,the purified induced SGC-like cells were transplanted into the full-thickness scalded wounds of the nude mice,after 4 weeks,the reconstructed SG-like structures were identified by immunohistochemical and immunofiuorescence analysis.Results A part of HFSCs in experimental group finally expressed SGCs phenotypes,by contrast,the control group 1 which just containing dermis-like mesenchymal tissue failed and the control group 2 consisted of heat shocked SGCs was in a poor efficiency; by immunofluorescence staining and flow cytometry analysis,the expression of HFSCs special biomarkers was down regulated,instead of the positive efficiency of SGCs special antigens increased; besides,the induced SGCs displayed a high expression of ectodysplasin A (EDA) and ectodysplasin A receptor (EDAR) genes and proteins; after cell transplantation,the youngest SG-like structures formed and be positive in SGCs special antigens,which never happened in untreated wounds (P <0.05).Conclusion The HFSCs are multipotential and capable in differentiating into SGCs which promise a potential stem cells reservoir for future use; our special co-culture microenvironment is promising for HFSCs differentiating; the induced SGCs are functional and could work well in the regeneration of SGs.

  5. The Fate of the Spiral Ganglion Cells After the Cochlear Hair Cells Serious Injuried%耳蜗毛细胞严重缺失后螺旋神经节细胞的病理变化

    Institute of Scientific and Technical Information of China (English)

    王建军; 毛华杰; 董吕华; 翟所强; 马龙

    2013-01-01

    Objective To study morphological changes of spiral ganglion cells (SGN) following severe cochlear hair cells injury. Methods Guinea pigs were given kanamycin sulfate (1000 mg/kg) intramuscularly followed by furosemide (100 mg/kg) intravenously 2 hours later. Auditory brainstem responses (ABRs) and cochlear morphology were examined at 3 days, 7 days, 1 month and 2 months respectively after the treatment. Results ABR thresholds were greatly elevated after the treatment, with no significant difference among the different time groups. Scanning electron microscopy revealed severe damage to cochlear hair cells, especially out hair cells (OHC) after 7 days. There was also extensive loss of inner hair cells in animals with severe auditory function damage while supporting cells in the organ of Corti were preserved. The SGN showed no change on Day 7, al-though severe SGN loss was seen after 1 month, with total collapse of the organ of Corti. Conclusion Drug-induced hearing loss starts with hair cell loss, followed by SGN loss. In addition, the extent of SGN damage seems to correlate to time lapse after drug administration and can take years to develop, which may provide a time window for cochlear implant.%目的:观察耳蜗毛细胞严重损伤后螺旋神经节细胞的病变过程。方法豚鼠肌肉注射硫酸卡那霉素(1000mg/kg)2小时后给予速尿(100mg/kg)静脉注射,分别于用药3天、7天、1月及2月行听觉脑干诱发电位(auditory brainstem response ABR)及耳蜗形态学检测。结果联合应用速尿和硫酸卡那霉素后,豚鼠鼠ABR阈值出现很大程度提高,给药3天、7天、1月、2个月组各频率ABR阈值比较无差别;对药物损伤致聋豚鼠进行耳蜗切片、扫描电镜观察,发现用药7天后耳蜗毛细胞严重受损,以外毛细胞(OHCs)缺失为主,严重致聋的豚鼠内毛细胞(IHCs)也广泛缺失,但是切片显示柯替氏器的支持细胞存在;螺旋神

  6. Identifying components of the hair-cell interactome involved in cochlear amplification

    Directory of Open Access Journals (Sweden)

    Cheatham MaryAnn

    2009-03-01

    Full Text Available Abstract Background Although outer hair cells (OHCs play a key role in cochlear amplification, it is not fully understood how they amplify sound signals by more than 100 fold. Two competing or possibly complementary mechanisms, stereocilia-based and somatic electromotility-based amplification, have been considered. Lacking knowledge about the exceptionally rich protein networks in the OHC plasma membrane, as well as related protein-protein interactions, limits our understanding of cochlear function. Therefore, we focused on finding protein partners for two important membrane proteins: Cadherin 23 (cdh23 and prestin. Cdh23 is one of the tip-link proteins involved in transducer function, a key component of mechanoelectrical transduction and stereocilia-based amplification. Prestin is a basolateral membrane protein responsible for OHC somatic electromotility. Results Using the membrane-based yeast two-hybrid system to screen a newly built cDNA library made predominantly from OHCs, we identified two completely different groups of potential protein partners using prestin and cdh23 as bait. These include both membrane bound and cytoplasmic proteins with 12 being de novo gene products with unknown function(s. In addition, some of these genes are closely associated with deafness loci, implying a potentially important role in hearing. The most abundant prey for prestin (38% is composed of a group of proteins involved in electron transport, which may play a role in OHC survival. The most abundant group of cdh23 prey (55% contains calcium-binding domains. Since calcium performs an important role in hair cell mechanoelectrical transduction and amplification, understanding the interactions between cdh23 and calcium-binding proteins should increase our knowledge of hair cell function at the molecular level. Conclusion The results of this study shed light on some protein networks in cochlear hair cells. Not only was a group of de novo genes closely associated

  7. MicroRNA-148b promotes proliferation of hair follicle cells by targeting NFAT5

    Directory of Open Access Journals (Sweden)

    Wanbao YANG,Qinqun LI,Bo SU,Mei YU

    2016-03-01

    Full Text Available MicroRNAs (miRNAs, small non-coding RNAs, are involved in many aspects of biological processes. Previous studies have indicated that miRNAs are important for hair follicle development and growth. In our study, we found by qRT-PCR that miR-148b was significantly upregulated in sheep wool follicle bulbs in anagen phase compared with the telogen phase of the hair follicle cycle. Overexpression of miR-148b promoted proliferation of both HHDPC and HHGMC. By using the TOPFlash system we demonstrated that miR-148b could activate Wnt/β-catenin pathway and b-catenin, cycD, c-jun and PPARD were consistently upregulated accordingly. Furthermore, transcript factor nuclear factor of activated T cells type 5 (NFAT5 and Wnt10b were predicted to be the target of miR-148b and this was substantiated using a Dual-Luciferase reporter system. Subsequently NFAT5 was further identified as the target of miR-148b using western blotting. These results were considered to indicate that miR-148b could activate the Wnt/β-catenin signal pathway by targeting NFAT5 to promote the proliferation of human hair follicle cells.

  8. 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.

  9. 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.

  10. 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...

  11. Inhibition of voltage-gated calcium currents in type II vestibular hair cells by cinnarizine.

    Science.gov (United States)

    Arab, Sonja F; Düwel, Philip; Jüngling, Eberhard; Westhofen, Martin; Lückhoff, Andreas

    2004-06-01

    Cinnarizine is pharmaceutically used in conditions with vestibular vertigo such as Meniere's disease. It is thought to act on extra-vestibular targets. We hypothesized that cinnarizine, as a blocker of L-type Ca2+ channels, may directly target vestibular hair cells where Ca2+ currents are important for the mechano-electrical transduction and transmitter release. Our aim was to clarify whether cinnarizine affected voltage-dependent Ca2+ currents in vestibular type II hair cells. Such cells were isolated from inner ears of guinea pigs by enzymatic and mechanical dissection from the gelatinous otolithic membrane and studied with the patch-clamp technique in conventional whole-cell mode. Ca2+ currents were elicited by depolarizing pulses in a solution containing 1.8 mM Ca2+ and 40 mM Ba2+. These currents resembled L-type currents (I(Ca,L)) with respect to their voltage-dependence and their inhibition by nifedipine and Cd2+ but did not show time-dependent inactivation. The currents were inhibited by cinnarizine in a concentration-dependent and reversible manner. The IC50 was 1.5 microM. A block exceeding 80% was achieved with 10 microM. The onset of current block was faster with higher concentrations but the reversibility after wash-out was less, suggesting accumulation in the membrane. We conclude that these direct actions of cinnarizine on hair cells should be considered as molecular mechanisms contributing to therapeutic effects of cinnarizine in vertigo. PMID:15138660

  12. 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

  13. 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.

  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. 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...

  16. 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...... auditory display creation; data handling for auditory display systems; applications of auditory display....

  17. 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...

  18. Functional recovery of anterior semicircular canal afferents following hair cell regeneration in birds

    Science.gov (United States)

    Boyle, Richard; Highstein, Stephen M.; Carey, John P.; Xu, Jinping

    2002-01-01

    Streptomycin sulfate (1.2 g/kg i.m.) was administered for 5 consecutive days to 5-7-day-old white Leghorn chicks; this causes damage to semicircular canal hair cells that ultimately regenerate to reform the sensory epithelium. During the recovery period, electrophysiological recordings were taken sequentially from anterior semicircular canal primary afferents using an indentation stimulus of the canal that has been shown to mimic rotational stimulation. Chicks were assigned to an early (14-18 days; n = 8), intermediate (28-34 days; n = 5), and late (38-58 days; n = 4) period based on days after treatment. Seven untreated chicks, 15-67 days old, provided control data. An absence of background and indent-induced discharge was the prominent feature of afferents in the early period: only "silent" afferents were encountered in 5/8 experiments. In several of these chicks, fascicles of afferent fibers were seen extending up to the epithelium that was void of hair cells, and intra- and extracellular biocytin labeling revealed afferent processes penetrating into the supporting cell layer of the crista. In 3/8 chicks 74 afferents could be characterized, and they significantly differed from controls (n = 130) by having a lower discharge rate and a negligible response to canal stimulation. In the intermediate period there was considerable variability in discharge properties of 121 afferents, but as a whole the number of "silent" fibers in the canal nerve diminished, the background rate increased, and a response to canal stimulation detected. Individually biocytin-labeled afferents had normal-appearing terminal specializations in the sensory epithelium by 28 days poststreptomycin. In the late period, afferents (n = 58) remained significantly different from controls in background discharge properties and response gain. The evidence suggests that a considerable amount of variability exists between chicks in the return of vestibular afferent function following ototoxic injury and

  19. 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.

  20. Interactions between hair cells shape spontaneous otoacoustic emissions in a model of the tokay gecko's cochlea.

    Directory of Open Access Journals (Sweden)

    Michael Gelfand

    Full Text Available BACKGROUND: The hearing of tetrapods including humans is enhanced by an active process that amplifies the mechanical inputs associated with sound, sharpens frequency selectivity, and compresses the range of responsiveness. The most striking manifestation of the active process is spontaneous otoacoustic emission, the unprovoked emergence of sound from an ear. Hair cells, the sensory receptors of the inner ear, are known to provide the energy for such emissions; it is unclear, though, how ensembles of such cells collude to power observable emissions. METHODOLOGY AND PRINCIPAL FINDINGS: We have measured and modeled spontaneous otoacoustic emissions from the ear of the tokay gecko, a convenient experimental subject that produces robust emissions. Using a van der Pol formulation to represent each cluster of hair cells within a tonotopic array, we have examined the factors that influence the cooperative interaction between oscillators. CONCLUSIONS AND SIGNIFICANCE: A model that includes viscous interactions between adjacent hair cells fails to produce emissions similar to those observed experimentally. In contrast, elastic coupling yields realistic results, especially if the oscillators near the ends of the array are weakened so as to minimize boundary effects. Introducing stochastic irregularity in the strength of oscillators stabilizes peaks in the spectrum of modeled emissions, further increasing the similarity to the responses of actual ears. Finally, and again in agreement with experimental findings, the inclusion of a pure-tone external stimulus repels the spectral peaks of spontaneous emissions. Our results suggest that elastic coupling between oscillators of slightly differing strength explains several properties of the spontaneous otoacoustic emissions in the gecko.

  1. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival

    Science.gov (United States)

    Wallis, Deeann; Hamblen, Melanie; Zhou, Yi; Venken, Koen J T.; Schumacher, Armin; Grimes, H. Leighton; Zoghbi, Huda Y.; Orkin, Stuart H.; Bellen, Hugo J.

    2003-01-01

    Gfi1 was first identified as causing interleukin 2-independent growth in T cells and lymphomagenesis in mice. Much work has shown that Gfi1 and Gfi1b, a second mouse homolog, play pivotal roles in blood cell lineage differentiation. However, neither Gfi1 nor Gfi1b has been implicated in nervous system development, even though their invertebrate homologues, senseless in Drosophila and pag-3 in C. elegans are expressed and required in the nervous system. We show that Gfi1 mRNA is expressed in many areas that give rise to neuronal cells during embryonic development in mouse, and that Gfi1 protein has a more restricted expression pattern. By E12.5 Gfi1 mRNA is expressed in both the CNS and PNS as well as in many sensory epithelia including the developing inner ear epithelia. At later developmental stages, Gfi1 expression in the ear is refined to the hair cells and neurons throughout the inner ear. Gfi1 protein is expressed in a more restricted pattern in specialized sensory cells of the PNS, including the eye, presumptive Merkel cells, the lung and hair cells of the inner ear. Gfi1 mutant mice display behavioral defects that are consistent with inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. They have a unique inner ear phenotype in that the vestibular and cochlear hair cells are differentially affected. Although Gfi1-deficient mice initially specify inner ear hair cells, these hair cells are disorganized in both the vestibule and cochlea. The outer hair cells of the cochlea are improperly innervated and express neuronal markers that are not normally expressed in these cells. Furthermore, Gfi1 mutant mice lose all cochlear hair cells just prior to and soon after birth through apoptosis. Finally, by five months of age there is also a dramatic reduction in the number of cochlear neurons. Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss

  2. Hair cell-type dependent expression of basolateral ion channels shapes response dynamics in the frog utricle

    Directory of Open Access Journals (Sweden)

    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.

  3. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis.

    Science.gov (United States)

    Ito, Mayumi; Liu, Yaping; Yang, Zaixin; Nguyen, Jane; Liang, Fan; Morris, Rebecca J; Cotsarelis, George

    2005-12-01

    The discovery of long-lived epithelial stem cells in the bulge region of the hair follicle led to the hypothesis that epidermal renewal and epidermal repair after wounding both depend on these cells. To determine whether bulge cells are necessary for epidermal renewal, here we have ablated these cells by targeting them with a suicide gene encoding herpes simplex virus thymidine kinase (HSV-TK) using a Keratin 1-15 (Krt1-15) promoter. We show that ablation leads to complete loss of hair follicles but survival of the epidermis. Through fate-mapping experiments, we find that stem cells in the hair follicle bulge do not normally contribute cells to the epidermis which is organized into epidermal proliferative units, as previously predicted. After epidermal injury, however, cells from the bulge are recruited into the epidermis and migrate in a linear manner toward the center of the wound, ultimately forming a marked radial pattern. Notably, although the bulge-derived cells acquire an epidermal phenotype, most are eliminated from the epidermis over several weeks, indicating that bulge stem cells respond rapidly to epidermal wounding by generating short-lived 'transient amplifying' cells responsible for acute wound repair. Our findings have implications for both gene therapy and developing treatments for wounds because it will be necessary to consider epidermal and hair follicle stem cells as distinct populations.

  4. Autosomal recessive hereditary auditory neuropathy

    Institute of Scientific and Technical Information of China (English)

    王秋菊; 顾瑞; 曹菊阳

    2003-01-01

    Objectives: Auditory neuropathy (AN) is a sensorineural hearing disorder characterized by absent or abnormal auditory brainstem responses (ABRs) and normal cochlear outer hair cell function as measured by otoacoustic emissions (OAEs). Many risk factors are thought to be involved in its etiology and pathophysiology. Three Chinese pedigrees with familial AN are presented herein to demonstrate involvement of genetic factors in AN etiology. Methods: Probands of the above - mentioned pedigrees, who had been diagnosed with AN, were evaluated and followed up in the Department of Otolaryngology Head and Neck Surgery, China PLA General Hospital. Their family members were studied and the pedigree diagrams were established. History of illness, physical examination,pure tone audiometry, acoustic reflex, ABRs and transient evoked and distortion- product otoacoustic emissions (TEOAEs and DPOAEs) were obtained from members of these families. DPOAE changes under the influence of contralateral sound stimuli were observed by presenting a set of continuous white noise to the non - recording ear to exam the function of auditory efferent system. Some subjects received vestibular caloric test, computed tomography (CT)scan of the temporal bone and electrocardiography (ECG) to exclude other possible neuropathy disorders. Results: In most affected subjects, hearing loss of various degrees and speech discrimination difficulties started at 10 to16 years of age. Their audiological evaluation showed absence of acoustic reflex and ABRs. As expected in AN, these subjects exhibited near normal cochlear outer hair cell function as shown in TEOAE & DPOAE recordings. Pure- tone audiometry revealed hearing loss ranging from mild to severe in these patients. Autosomal recessive inheritance patterns were observed in the three families. In Pedigree Ⅰ and Ⅱ, two affected brothers were found respectively, while in pedigree Ⅲ, 2 sisters were affected. All the patients were otherwise normal without

  5. 丁胺卡那霉素对豚鼠耳蜗毛细胞凋亡及听力阈值的影响%Effect of amikacin on the cochlear hair cells and hearing threshold ofguinea pigs

    Institute of Scientific and Technical Information of China (English)

    巴云鹏; 董明敏

    2000-01-01

    Aifr: To investigate the cochlear hair cell apoptosis induced by the ototoxic aminoglycoside antibiotic amikacinand the effect of hair cell apoptosis on heating loss in guinea pigs. Methods: Fifteen guinea pigs were randomly divided into 3groups, which had been intramuscularly injected with amikacin for 1 day, 3 days and 6 days respectively before they were put todeath. Auditory brainstem response (ABR) and the apoptosis of cochlea hair cells were examined with TdT-modided biotin-dUTPNick-end labeling( TUNEL) at different times. Results: ①In normal cochlear hair cells, no apoptic cell were generally noted. In3 groups the morphological changes of the cell apoptosis were noted at 1,3 and 6 days after injection with amikacin; ②ABRthreshold had no obvious changes 1,3 days after using amikacin while an elevation of ABR threshold was noted after using amikacinfor 6 successive days in guinea pigs. C orclusion: ① Amikacin can induce the apoptosis of the cochlear hair cells in guinea pigs.Cell apoptosis was a mode of hair cell loss after injection with amikacin in guinea pigs. ② The ototoxin mechanism of the amino-glycoside antibiotic may be related to apoptosis of the cochlear hair cell induced by itself.%目的:探讨丁胺卡那霉素作用于耳蜗系统时毛细胞凋亡现象及其在听力损伤中的作用。方法:15只豚鼠随机分为3组,各组肌内注射丁胺卡那霉素400mg·kg-1·d-1,分别于用药1 d,3 d,6 d后处死。处死前检测其听脑于反应(auditory brainstem responses,ABR)的变化,并利用光镜和TUNEL标记技术检测耳蜗毛细胞发生凋亡的情况。结果:①豚鼠肌内注射丁胺卡那霉素1 d后耳蜗毛细胞即出现凋亡现象,连续用药3~6 d,毛细胞凋亡呈强阳性表达;②耳蜗毛细胞凋亡出现的早期豚鼠听力阈值无明显改变,连续用药6 d后听力阈值则明显提高。结论:①丁胺卡那霉素作用于耳蜗毛细胞可引起毛细胞凋亡,细胞

  6. Bax, Bcl2, and p53 differentially regulate neomycin- and gentamicin-induced hair cell death in the zebrafish lateral line.

    Science.gov (United States)

    Coffin, Allison B; Rubel, Edwin W; Raible, David W

    2013-10-01

    Sensorineural hearing loss is a normal consequence of aging and results from a variety of extrinsic challenges such as excessive noise exposure and certain therapeutic drugs, including the aminoglycoside antibiotics. The proximal cause of hearing loss is often death of inner ear hair cells. The signaling pathways necessary for hair cell death are not fully understood and may be specific for each type of insult. In the lateral line, the closely related aminoglycoside antibiotics neomycin and gentamicin appear to kill hair cells by activating a partially overlapping suite of cell death pathways. The lateral line is a system of hair cell-containing sense organs found on the head and body of aquatic vertebrates. In the present study, we use a combination of pharmacologic and genetic manipulations to assess the contributions of p53, Bax, and Bcl2 in the death of zebrafish lateral line hair cells. Bax inhibition significantly protects hair cells from neomycin but not from gentamicin toxicity. Conversely, transgenic overexpression of Bcl2 attenuates hair cell death due to gentamicin but not neomycin, suggesting a complex interplay of pro-death and pro-survival proteins in drug-treated hair cells. p53 inhibition protects hair cells from damage due to either aminoglycoside, with more robust protection seen against gentamicin. Further experiments evaluating p53 suggest that inhibition of mitochondrial-specific p53 activity confers significant hair cell protection from either aminoglycoside. These results suggest a role for mitochondrial p53 activity in promoting hair cell death due to aminoglycosides, likely upstream of Bax and Bcl2.

  7. 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

  8. 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-...

  9. What shapes the stimulus to the inner hair cell?: A moderated discussion

    Science.gov (United States)

    Fridberger, Anders; Guinan, John J.

    2015-12-01

    The following is an edited transcript of a recorded discussion session on the topic of "What Shapes the Stimulus to the Inner Hair Cell?". The discussion, moderated by the authors, took place at the 12th International Workshop on the Mechanics of Hearing held at Cape Sounio, Greece, in June 2014. All participants knew that the session was being recorded. In view of both the spontaneous nature of the discussion and the editing, however, this transcript may not represent the considered or final views of the participants, and may not represent a consensus of experts in the field. The reader is advised to consult additional independent publications.

  10. 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

  11. 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...

  12. Dry hair

    Science.gov (United States)

    ... normally style your hair? Do you use a hair dryer? What type? How often? What other symptoms are also present? Diagnostic tests that may be performed include: Examination of the hair under a microscope Blood tests

  13. 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.

  14. Theory of electrically driven shape changes of cochlear outer hair cells.

    Science.gov (United States)

    Dallos, P; Hallworth, R; Evans, B N

    1993-07-01

    1. A theory of cochlear outer hair cell electromotility is developed and specifically applied to somatic shape changes elicited in a microchamber. The microchamber permits the arbitrary electrical and mechanical partitioning of the outer hair cell along its length. This means that the two partitioned segments are stimulated with different input voltages and undergo different shape changes. Consequently, by imposing more constraints than other methods, experiments in the microchamber are particularly suitable for testing different theories of outer hair cell motility. 2. The present model is based on simple hypotheses. They include a distributed motor associated with the cell membrane or cortex and the assumption that the displacement generated by the motor is related to the transmembrane voltage across the associated membrane element. It is expected that the force generated by the motor is counterbalanced by an elastic restoring force indigenous to the cell membrane and cortex, and a tensile force due to intracellular pressure. It is assumed that all changes take place while total cell volume is conserved. The above elements of the theory taken together permit the development of qualitative and quantitative predictions about the expected motile responses of both partitioned segments of the cell. Only a DC treatment is offered here. 3. Both a linear motor and an expanded treatment that incorporates a stochastic molecular motor model are considered. The latter is represented by a two-state Boltzmann process. We show that the linear motor treatment is an appropriate extrapolation of the stochastic motor theory for the case of small voltage driving signals. Comparison of experimental results with model responses permits the estimation of model parameters. Good match of data is obtained if it is assumed that the molecular motors undergo conformational length changes of 0.7-1.0 nm, that they have an effective displacement vector at approximately -20 degrees with the long

  15. 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

  16. 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.

  17. 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.

  18. 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. ...

  19. 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.

  20. Fabrication and characterization of artificial hair cell sensor based on MWCNT-PDMS composite

    Science.gov (United States)

    Kim, Chi Yeon; Lee, Hyun Sup; Cho, Yo Han; Joh, Cheeyoung; Choi, Pyung; Park, Seong Jin

    2011-06-01

    The aim of this work is to design and fabricate a flow sensor using an artificial hair cell (AHC) inspired by biological hair cells of fish. The sensor consists of a single cilium structure with high aspect ratio and a mechanoreceptor using force sensitive resistor (FSR). The cilium structure is designed for capturing a drag force with direction due to flow field around the sensor and the mechanoreceptor is designed for sensing the drag force with direction from the cilium structure and converting it into an electric signal. The mechanoreceptor has a symmetric four electrodes to sense the drag force and its direction. To fabricate the single cilium structure with high aspect ratio, we have proposed a new design concept using a separated micro mold system (SMS) fabricated by the LIGA process. For a successful replication of the cilium structure, we used the hot embossing process with the help of a double-sided mold system. We used a composite of multiwall carbon nanotube and polydimethylsiloxane (MWCNT-PDMS). The performance of the mechanoreceptors was measured by a computer-controlled nanoindenter. We carried out several experiments with the sensor in the different flow rate and direction using the experimental test apparatus. To calibrate the sensor and calculate the velocity with direction based the signal from the sensor, we analyzed the coupled phenomena between flow field and the cilium structure to calculate the deflection of the cilium structure and the drag force applying to the cilium structure due to the flow field around sensor.

  1. 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

  2. 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.

  3. 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...

  4. Amiloride causes changes in the mechanical properties of hair cell bundles in the fish lateral line similar to those induced by dihydrostreptomycin

    NARCIS (Netherlands)

    Wiersinga-Post, JEC; van Netten, SM

    1998-01-01

    Amiloride is a known blocker of the mechano-electrical transduction current in sensory hair cells. Measurements of cupular motion in the lateral line organ of fish now show that amiloride concurrently changes the micromechanical properties of the hair cell bundles. The effects of amiloride on the me

  5. 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

  6. 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....

  7. [Hair follicle regeneration].

    Science.gov (United States)

    Itami, Satoshi

    2008-05-01

    Hair growth cycle is coordinated with complex processes that are dependent on the interactions of follicular stem cells and dermal papilla cells (DPCs). For the past 10 years, the developmental mechanism of hair follicles has been extensively studied, and spatial and temporal expressions of many molecules are required for the hair morphogenesis. These molecules are also required for hair cycle progression. Androgen receptor, which is a ligand dependent transcription factor, plays an important role in human hair cycle. Frontal scalp DPCs from androgenetic alopecia (AGA) are the target cells of androgen action. Minoxidil and Finasteride were recently introduced for the treatment of AGA, and cell therapy using DPCs is a next strategy for the innovative treatment. PMID:18464507

  8. 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 ...

  9. 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

  10. 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...

  11. Autoradiographic studies of synapsis formation on regenerated hair cells in the chich cochlea%小鸡再生听毛细胞及其突触连接的放射自显影

    Institute of Scientific and Technical Information of China (English)

    聂国辉; 汪吉宝

    2000-01-01

    . It was localized on the neuclei of regenerated hair cells. Neural synapses were found at the end of the new hair cells. The synapses contained many mitochondrions and vesicles. They looked like efferent synapses. Conclusion These results showed a potential capability of cellular proliferation in damaged auditory epithelia. Some of the supporting cells in the damaged region could be precusors for regenerating hair cells. The restoration of hair cell numbers following gentamicin toxicity result from the production of new cells by mitosis. The present results provide a direct evidence of innervation to hair cells after regeneration.

  12. 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.

  13. 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

  14. 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

  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

    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...... the 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...

  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. Entropical Aspects in Auditory Processes and Psychoacoustical Law of Weber-Fechner

    Science.gov (United States)

    Cosma, I.; Popescu, D. I.

    For hearing sense, the mechanoreceptors fire action potentials when their membranes are physically stretched. Based on the statistical physics, we analyzed the entropical aspects in auditory processes of hearing. We develop a model that connects the logarithm of relative intensity of sound (loudness) to the level of energy disorder within the system of cellular sensory system. The increasing of entropy and disorder in the system is connected to the free energy available to signal the production of action potentials in inner hair cells of the vestibulocochlear auditory organ.

  19. Temperature dependency of cupular mechanics and hair cell frequency selectivity in the fish canal lateral line organ

    NARCIS (Netherlands)

    Wiersinga-Post, JEC; van Netten, SM

    2000-01-01

    The mechanical frequency selectivity of the cupula located in the supraorbital lateral line canal and the frequency selectivity of the hair cells driven by the cupula were measured simultaneously in vivo. Laser interferometry was used to measure cupular mechanics and extracellular receptor potential

  20. Amino acid substitution converts WEREWOLF function from an activator to a repressor of Arabidopsis non-hair cell development.

    Science.gov (United States)

    Tominaga-Wada, Rumi; Nukumizu, Yuka; Wada, Takuji

    2012-02-01

    Root hair cell or non-hair cell fate determination in Arabidopsis thaliana root epidermis is model system for plant cell development. Two types of MYB transcription factors, the R2R3-type MYB, WEREWOLF (WER), and an R3-type MYB, CAPRICE (CPC), are involved in this cell fate determination process. To study the molecular basis of this process, we analyzed the functional relationship of WER and CPC. WER-CPC chimeric constructs were made from WER where all or parts of the MYB R3 region were replaced with the corresponding regions from CPC R3, and the constructs were introduced into the cpc-2 mutant. Although, the WER gene did not rescue the cpc-2 mutant 'small number of root hairs' phenotype, the WER-CPC chimera with two amino acids substitution (WC6) completely rescued the cpc-2 mutant phenotype. Furthermore, the WER-CPC chimera with 37 amino acids substitution (WC5) excessively rescued the cpc-2 mutant and induced 2.5 times more root hairs than wild-type. Consistent with this phenotype, GL2 gene expression was strongly reduced in WC5 in a cpc-2 background. Our results suggest that swapping at least two amino acids is sufficient to convert WER to CPC function. Therefore, these key residues may have strongly contributed to the selection of these important functions over evolution.

  1. Frequency-dependent properties of a fluid jet stimulus : Calibration, modeling, and application to cochlear hair cell bundles

    NARCIS (Netherlands)

    Dinklo, Theo; Meulenberg, Cecil J. W.; van Netten, Sietse M.

    2007-01-01

    The investigation of small physiological mechanosensory systems, such as hair cells or their accessory structures in the inner ear or lateral line organ, requires mechanical stimulus equipment that allows spatial manipulation with micrometer precision and stimulation with amplitudes down to the nano

  2. 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.

  3. 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

  4. System approaches to study root hairs as a single cell plant model: current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Md Shakhawat eHossain

    2015-05-01

    Full Text Available Our current understanding of plant functional genomics derives primarily from measurements of gene, protein and/or metabolite levels averaged over the whole plant or multicellular tissues. These approaches risk diluting the response of specific cells that might respond strongly to the treatment but whose signal is diluted by the larger proportion of non-responding cells. For example, if a gene is expressed at a low level, does this mean that it is indeed lowly expressed or is it highly expressed, but only in a few cells? In order to avoid these issues, we adopted the soybean root hair cell, derived from a single, differentiated root epidermal cell, as a single-cell model for functional genomics. Root hair cells are intrinsically interesting since they are major conduits for root water and nutrient uptake and are also the preferred site of infection by nitrogen-fixing rhizobium bacteria. Although a variety of other approaches have been used to study single plant cells or single cell types, the root hair system is perhaps unique in allowing application of the full repertoire of functional genomic and biochemical approaches. In this mini review, we summarize our published work and place this within the broader context of root biology, with a significant focus on understanding the initial events in the soybean-rhizobium interaction.

  5. 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.

  6. Characteristics of echolocating bats’auditory stereocilia length, compared with other mammals

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The stereocilia of the Organ of Corti in 4 different echolocating bats, Myotis adversus, Murina leuco-gaster, Nyctalus plancyi (Nyctalus velutinus), and Rhinolophus ferrumequinum were observed by using scanning electron microscopy (SEM). Stereocilia lengths were estimated for comparison with those of non-echolocating mammals. The specialized lengths of outer hair cells (OHC) stereocilia in echolocating bats were shorter than those of non-echolocating mammals. The specialized lengths of inner hair cells (IHC) stereocilia were longer than those of outer hair cells stereocilia in the Organ of Corti of echolocating bats. These characteristics of the auditory stereocilia length of echolocating bats represent the fine architecture of the electromotility process, helping to adapt to high frequency sound and echolocation.

  7. Characteristics of echolocating bats' auditory stereocilia length, compared with other mammals

    Institute of Scientific and Technical Information of China (English)

    YAO Qian; ZENG JinYao; ZHENG YongMei; Julia LATHAM; LIANG Bing; JIANG Lei; ZHANG ShuYi

    2007-01-01

    The stereocilia of the Organ of Corti in 4 different echolocating bats, Myotis adversus, Murina leucogaster, Nyctalus plancyi (Nyctalus velutinus), and Rhinolophus ferrumequinum were observed by using scanning electron microscopy (SEM). Stereocilia lengths were estimated for comparison with those of non-echolocating mammals. The specialized lengths of outer hair cells (OHC) stereocilia in echolocating bats were shorter than those of non-echolocating mammals. The specialized lengths of inner hair cells (IHC) stereocilia were longer than those of outer hair cells stereocilia in the Organ of Corti of echolocating bats. These characteristics of the auditory stereocilia length of echolocating bats represent the fine architecture of the electromotility process, helping to adapt to high frequency sound and echolocation.

  8. Consequences of outer hair cell damage for otoacoustic emissions and audio-vocal feedback in the mustached bat.

    Science.gov (United States)

    Kössl, M; Vater, M

    2000-12-01

    The cochlea of the mustached bat is adapted to process ultrasonic echolocation signals. To assess the involvement of active sound amplification by outer hair cells in high-frequency hearing and in audio-vocal interaction, selective hair cell damage was induced by the antibiotic Amikacin. Amikacin preferentially damaged the first row of outer hair cells in the basal cochlear turn. The cochlear regions coding for the second-harmonic constant-frequency component of the echolocation call (CF2) at 61 kHz and for frequencies between 75 and 100 kHz were the most affected. This was reflected in an increase of mechanical thresholds obtained by measuring distortion-product otoacoustic emissions. During initial periods of minor hair cell damage, when thresholds had deteriorated by less than 40 dB, a sharp, mechanical, cochlear resonance that is responsible for enhanced tuning to 61 kHz was still measurable as a stimulus-frequency otoacoustic emission and its frequency decreased by 350 Hz. The persistence of the resonance suggests that passive structures like the tectorial or basilar membrane are important for generation of the resonance. Behaviorally, the bats reacted to the change in cochlear micromechanics with a decrease of their CF2 frequency by 360 Hz. After larger hair cell damage, when the cochlear resonance had disappeared, the bats vocalized only sparsely and the CF2 frequency increased by up to 2 kHz, which may correspond to a state without audiovocal feedback. This indicates that audio-vocal feedback in the nondamaged animal works to lower the call frequency. PMID:11547810

  9. Noise-induced nitrotyrosine increase and outer hair cell death in guinea pig cochlea

    Institute of Scientific and Technical Information of China (English)

    HAN Wei-ju; SHI Xiao-rui; Alfred Nuttall

    2013-01-01

    Background Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss,and a number of studies showed the appearance of increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) during and after noise exposure.This study was designed to investigate the noise exposure induced nitrotyrosine change and the mechanism of outer hair cells death in guinea pig cochlea.Method Thirty guinea pigs were used in this study.The experimental animals were either exposed for 4 hours per day to broadband noise at 122 dB SPL (A-weighted) for 2 consecutive days or perfused cochleae with 5 mg/ml of the SIN1 solutions,an exogenous NO and superoxide donor,for 30 minutes.Then the cochleae of the animals were dissected.Propidium iodide (PI),a DNA intercalating fluorescent probe,was used to trace morphological changes in OHC nuclei.The distribution of nitrotyrosine (NT) in the organ of Corti and the cochlear lateral wall tissue from the guinea pigs were examined using fluorescence immunohistochemistry method.Whole mounts of organ of Corti were prepared.Morphological and fluorescent changes were examined under a confocal microscope.Results Either after noise exposure or after SIN1 perfusion,outer hair cells (OHCs) death with characteristics of both apoptotic and necrotic degradation appeared.Nitrotyrosine immunolabeling could be observed in the OHCs from the control animals.After noise exposure,NT immunostaining became much greater than the control animals in OHCs.The apoptotic OHC has significant increase of nitrotyrosine in and around the nucleus following noise exposure.In the normal later wall of cochleae,relatively weak nitrotyrosine immunolabeling could be observed.After noise exposure,nitrotyrosine immunoactivity became stronger in stria vascularis.Conclusion Noise exposure induced increase of nitrotyrosine production is associated with OHCs death suggesting reactive nitrogen species participation in the cochlear

  10. Dynamics of Lgr6+ Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis

    Science.gov (United States)

    Füllgrabe, Anja; Joost, Simon; Are, Alexandra; Jacob, Tina; Sivan, Unnikrishnan; Haegebarth, Andrea; Linnarsson, Sten; Simons, Benjamin D.; Clevers, Hans; Toftgård, Rune; Kasper, Maria

    2015-01-01

    Summary 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. PMID:26607954

  11. The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration.

    Science.gov (United States)

    Chen, Chih-Chiang; Plikus, Maksim V; Tang, Pin-Chi; Widelitz, Randall B; Chuong, Cheng Ming

    2016-04-10

    Hair and feathers are unique because (1) their stem cells are contained within a follicle structure, (2) they undergo cyclic regeneration repetitively throughout life, (3) regeneration occurs physiologically in healthy individuals and (4) regeneration is also induced in response to injury. Precise control of this cyclic regeneration process is essential for maintaining the homeostasis of living organisms. While stem cells are regulated by the intra-follicle-adjacent micro-environmental niche, this niche is also modulated dynamically by extra-follicular macro-environmental signals, allowing stem cells to adapt to a larger changing environment and physiological needs. Here we review several examples of macro-environments that communicate with the follicles: intradermal adipose tissue, innate immune system, sex hormones, aging, circadian rhythm and seasonal rhythms. Related diseases are also discussed. Unveiling the mechanisms of how stem cell niches are modulated provides clues for regenerative medicine. Given that stem cells are hard to manipulate, focusing translational therapeutic applications at the environments appears to be a more practical approach.

  12. 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.

  13. Direct effects of reactive oxygen species on cochlear outer hair cell shape in vitro.

    Science.gov (United States)

    Clerici, W J; DiMartino, D L; Prasad, M R

    1995-04-01

    Reactive oxygen species (ROS) have been implicated in the ototoxicity of various agents. This study examines the effects of superoxide anion (O2), hydroxyl radical (OH.) and hydrogen peroxide (H2O2), on isolated cochlear outer hair cell (OHC) morphology. OHCs were superfused with artificial perilymph (AP) or AP containing a specific ROS scavenger, and then with AP, ROS system or scavenger plus ROS system for 90 min. The generation of ROS as well as the scavenging properties of other agents were confirmed by specific biochemical assays. Control cells decreased 4.8% in mean length, and showed no obvious membrane damage. Generation of O2. or OH. resulted in high rates (85.7 and 42.9%, respectively) of bleb formation at the synaptic pole, and decreased (O2., 15.2%; OH., 17.3%) mean cell length. Length change and bleb formation rate were H2O2 concentration-dependent. 20 mM H2O2 led to 33.3% decreased mean cell length, and only 20% bleb formation; 0.1 mM H2O2 led to 83.3% bleb formation, with no length decrease. Superoxide dismutase, deferoxamine and catalase protected against O2., OH. and H2O2 effects, respectively. Bleb formation and diminished cell length likely represent differential lipid peroxidative outcomes at supra- and infranuclear membranes, and are consistent with effects of certain ototoxicants.

  14. 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.

  15. 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.

  16. 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...

  17. Inner ear hair cell regeneration A look from the past to the future

    Institute of Scientific and Technical Information of China (English)

    Francisco Santaolalla; Carlos Salvador; Agustn Martnez; Jose Mara Snchez; Ana Snchez del Rey

    2013-01-01

    Most recent studies on regeneration of inner ear hair cel s focus on use of stem cel s, gene therapy and neurotrophic factors. Cochlear gene therapy has been successful y used in the treatment of neu-rosensory hearing loss. This suggests that cochlear hair cel regeneration is possible. The objective of this paper is to review research and clinical application of inner near hair cel regeneration.

  18. 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.

  19. 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

  20. 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

  1. Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro

    Science.gov (United States)

    He, Zuhong; Sun, Shan; Waqas, Muhammad; Zhang, Xiaoli; Qian, Fuping; Cheng, Cheng; Zhang, Mingshu; Zhang, Shasha; Wang, Yongming; Tang, Mingliang; Li, Huawei; Chai, Renjie

    2016-01-01

    Aminoglycosides are ototoxic to the cochlear hair cells, and mitochondrial dysfunction is one of the major mechanisms behind ototoxic drug-induced hair cell death. TRMU (tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase) is a mitochondrial protein that participates in mitochondrial tRNA modifications, but the role of TRMU in aminoglycoside-induced ototoxicity remains to be elucidated. In this study, we took advantage of the HEI-OC-1 cell line to investigate the role of TRMU in aminoglycoside-induced cell death. We found that TRMU is expressed in both hair cells and HEI-OC-1 cells, and its expression is significantly decreased after 24 h neomycin treatment. We then downregulated TRMU expression with siRNA and found that cell death and apoptosis were significantly increased after neomycin injury. Furthermore, when we down-regulated TRMU expression, we observed significantly increased mitochondrial dysfunction and increased levels of reactive oxygen species (ROS) after neomycin injury, suggesting that TRMU regulates mitochondrial function and ROS levels. Lastly, the antioxidant N-acetylcysteine rescued the mitochondrial dysfunction and cell apoptosis that was induced by TRMU downregulation, suggesting that ROS accumulation contributed to the increased aminoglycosides sensitivity of HEI-OC-1 cells after TRMU downregulation. This study provides evidence that TRMU might be a new therapeutic target for the prevention of aminoglycoside-induced hair cell death. PMID:27405449

  2. 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....

  3. 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.

  4. 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

  5. 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.

  6. Acetylcholine-induced calcium oscillation in isolated outer hair cells in guinea pig

    Institute of Scientific and Technical Information of China (English)

    XIE Ding-hua; XIAO Zi-an; YANG Shu

    2006-01-01

    Abstract Objective This study is to explore the relationship between acetylcholine (ACh)-induced calcium release from intracellular Ca2+ stores and function of outer hair cell (OHC) motors, in an attempt to elucidate the mechanism of OHC electromotility at resting state. Methods OHCs were isolated from adult guinea pig (200-300 g) cochlea and loaded with Fluo-3/AM. The cells were treated with ACh/dHBSS, ACh/HBSS, dHBSS only or HBSS only. Intracellular [Ca2+]i variations in cells under the four treatments were observed using an Ar-Kr laser scan confocal microscope. Results [Ca2+]i oscillations were recorded in five OHCs treated with ACh/dHBSS but not in other cells. This is the first time that Ach-excited [Ca2+]i oscillations are reported in guinea pig OHCs independent of extracellular calcium. Conclusions ACh-excited [Ca2+]i oscillations in OHCs originates from intracellular calcium release and may play a crucial role in maintaining active mechanical motility of the OHC at resting and modulating OHC electromotility.

  7. ATP hydrolysis is critically required for function of CaV1.3 channels in cochlear inner hair cells via fueling Ca2+ clearance.

    Science.gov (United States)

    Weiler, Simon; Krinner, Stefanie; Wong, Aaron B; Moser, Tobias; Pangršič, Tina

    2014-05-14

    Sound encoding is mediated by Ca(2+) influx-evoked release of glutamate at the ribbon synapse of inner hair cells. Here we studied the role of ATP in this process focusing on Ca(2+) current through CaV1.3 channels and Ca(2+) homeostasis in mouse inner hair cells. Patch-clamp recordings and Ca(2+) imaging demonstrate that hydrolyzable ATP is essential to maintain synaptic Ca(2+) influx in inner hair cells via fueling Ca(2+)-ATPases to avoid an increase in cytosolic [Ca(2+)] and subsequent Ca(2+)/calmodulin-dependent inactivation of CaV1.3 channels.

  8. Hair removal

    DEFF Research Database (Denmark)

    Haedersdal, Merete; Haak, Christina S

    2011-01-01

    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...... 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......, 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...

  9. 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 ...

  10. Shape deformation of the organ of Corti associated with length changes of outer hair cell

    Science.gov (United States)

    Zimmermann, U.; Fermin, C.

    1996-01-01

    Cochlear outer hair cells (OHC) are commonly assumed to function as mechanical effectors as well as sensory receptors in the organ of Corti (OC) of the inner ear. OHC in vitro and in organ explants exhibit mechanical responses to electrical, chemical or mechanical stimulation which may represent an aspect of their effector process that is expected in vivo. A detailed description, however, of an OHC effector operation in situ is still missing. Specifically, little is known as to how OHC movements influence the geometry of the OC in situ. Previous work has demonstrated that the motility of isolated OHCs in response to electrical stimulation and to K(+)-gluconate is probably under voltage control and causes depolarisation (shortening) and hyperpolarization (elongation). This work was undertaken to investigate if the movements that were observed in isolated OHC, and which are induced by ionic stimulation, could change the geometry of the OC. A synchronized depolarization of OHC was induced in guinea pig cochleae by exposing the entire OC to artificial endolymph (K+). Subsequent morphometry of mid-modiolar sections from these cochleae revealed that the distance between the basilar membrane (BM) and the reticular lamina (RL) had decreased considerably. Furthermore, in the three upper turns OHC had significantly shortened in all rows. The results suggest that OHC can change their length in the organ of Corti (OC) thus deforming the geometry of the OC. The experiments reveal a tonic force generation within the OC that may change the position of RL and/or BM, contribute to damping, modulate the BM-RL-distance and control the operating points of RL and sensory hair bundles. Thus, the results suggest active self-adjustments of cochlear mechanics by slow OHC length changes. Such mechanical adjustments have recently been postulated to correspond to timing elements of animal communication, speech or music.

  11. 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...

  12. 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.

  13. 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

  14. Immunological identification of candidate proteins involved in regulating active shape changes of outer hair cells.

    Science.gov (United States)

    Knipper, M; Zimmermann, U; Köpschall, I; Rohbock, K; Jüngling, S; Zenner, H P

    1995-06-01

    By employing immunological methods, it has been demonstrated that myosin, myosin light chain (MLC) and myosin light chain kinase (MLCK) proteins in outer hair cells (OHC) are immunologically different from isoforms in platelets, smooth muscle and heart muscle, and are probably more related to isoforms found in red blood cells (RBC). Moreover, proteins related to band 3 protein (b3p) and protein 4.1 (p 4.1), ankyrin as well as fodrin and spectrin, but not glycophorin, have been identified in isolated OHCs. Both OHCs and RBC differ from other motile non-muscle cells in their lack of smooth muscle isoforms of actin, their common high levels of spectrin-, ankyrin- and band 3-like proteins, as well as the expression of the 80 kDa protein 4.1 isoform. The data support the notion that motility of OHC may be based upon regulation of the b3p/p 4.1/ankyrin complex, and thus may be reminiscent to the active shape changes in RBC.

  15. 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

  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

    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.

  17. Novel synthetic protective compound, KR-22335, against cisplatin-induced auditory cell death.

    Science.gov (United States)

    Shin, Yoo Seob; Song, Suk Jin; Kang, Sungun; Hwang, Hye Sook; Jung, Young-Sik; Kim, Chul-Ho

    2014-02-01

    Cisplatin [cis-diammine-dichloroplatinum (II)] is a widely used chemotherapeutic agent, and one of its most severe side effects is ototoxicity. In the course of developing a new protective agent against cisplatin-induced ototoxicity, we have been interested in a novel synthetic compound, 3-Amino-3-(4-fluoro-phenyl)-1H-quinoline-2,4-dione (KR-22335). We evaluated the effectiveness of KR-22335 as an otoprotective agent against cisplatin-induced toxicity. The otoprotective effect of KR-22335 against cisplatin was tested in vitro in cochlear organs of Corti-derived cell lines, HEI-OC1, and in vivo in a zebrafish (Danio rerio) model. Cisplatin-induced apoptosis, cell cycle arrest and an increase in intracellular reactive oxygen species (ROS) generation were demonstrated in HEI-OC1 cells. KR-22335 inhibited cisplatin-induced apoptosis and mitochondrial injury in HEI-OC1 cells. KR-22335 inhibited cisplatin-induced activation of JNK, p-38, caspase-3 and PARP in HEI-OC1 cells. Scanning and transmission electron micrographs showed that KR-22335 prevented cisplatin-induced destruction of kinocilium and stereocilia in zebrafish neuromasts. Tissue TUNEL of neuromasts in zebrafish demonstrated that KR-22335 blocked cisplatin-induced TUNEL positive hair cells in neuromasts. The results of this study suggest that KR-22335 may prevent ototoxicity caused by the administration of cisplatin through the inhibition of mitochondrial dysfunction and suppression of ROS generation. KR-22335 may be considered as a potential candidate for protective agents against cisplatin-induced ototoxicity.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. Effects of salicylate on shape, electromotility and membrane characteristics of isolated outer hair cells from guinea pig cochlea.

    Science.gov (United States)

    Shehata, W E; Brownell, W E; Dieler, R

    1991-01-01

    A reversible tinnitus and hearing loss have long been known to result from large doses of salicylate. Cochlear electrophysiology and otoacoustic emission studies suggest that the drug may interfere with outer hair cell electromotility. Exposure of isolated outer hair cells to sodium salicylate concentrations ranging from 0.05 to 10 mM reveals a dose dependent, reversible loss of turgidity and dimunition of electromotility. There was also a change in membrane conductance with salicylate superfusion that occurred later in time from the onset of shape and electromotility changes. There was no evidence of dose dependence for the change in membrane conductance, nor was the change reversible. The changes in shape and electromotility that we observe in vitro may impair cochlear partition movements in vivo and could account, at least in part, for the salicylate-induced hearing loss and effects on otoacoustic emissions.

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. Voltage- and calcium-dependent motility of saccular hair bundles

    Science.gov (United States)

    Quiñones, Patricia M.; Meenderink, Sebastiaan W. F.; Bozovic, Dolores

    2015-12-01

    Active bundle motility, which is hypothesized to supply feedback for mechanical amplification of signals, is thought to enhance sensitivity and sharpen tuning in vestibular and auditory organs. To study active hair bundle motility, we combined high-speed camera recordings of bullfrog sacculi, which were mounted in a two-compartment chamber, and voltage-clamp of the hair cell membrane potential. Using this paradigm, we measured three types of bundle motions: 1) spontaneous oscillations which can be analyzed to measure the physiological operating range of the transduction channel; 2) a sustained quasi-static movement of the bundle that depends on membrane potential; and 3) a fast, transient and asymmetric movement that resets the bundle position and depends on changes in the membrane potential. These data support a role for both calcium and voltage in the transduction-channel function.

  9. A threshold decrease for electrically stimulated motor responses of isolated aging outer hair cells from the pigmented guinea pig.

    Science.gov (United States)

    LePage, E L; Reuter, G; Zenner, H P

    1995-01-01

    When outer hair cells are isolated from guinea pig cochleas and are placed in normal Hank's medium, they exhibit aging as a slow tonic reduction in length and increase in diameter. During this time the lateral subsurface cisternae become progressively vesiculated and the optical density of the border seen under phase-contrast microscopy decreases. A study of 65 outer hair cells was carried out using video imaging of this process. The base of each cell bonded to the Petri dish and the motility of the cuticular plate was recorded in two ways. To quantify the slow contraction of each preparation, the dimensions of the cell were measured from video replay. Displacements of the cuticular plate in response to an alternating electric field in line with the cell axis were also monitored using a video tracking technique. The amplitude of a 1 Hz stimulus required to cause a visually detectable motor response above baseline noise decreased as the cell degraded. Typically, fresh cylindrical cells exhibiting high optical contrast showed relatively small movements for field strengths up to 2 kVm-1. However, as the cell depolarized, the rigidity initially decreased and the cell could respond to field strengths down to 0.1 kVm-1 before cell death ultimately occurred. Such a threshold phenomenon in the isolated OHC has not been demonstrated directly until now. This result explains the variability of electromotility in aging in vitro preparations from the cochlea. PMID:7546676

  10. 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...

  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. 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.

  13. 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

  14. 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

  15. Simulation of the response of the inner hair cell stereocilia bundle to an acoustical stimulus.

    Directory of Open Access Journals (Sweden)

    Sonya T Smith

    Full Text Available Mammalian hearing relies on a cochlear hydrodynamic sensor embodied in the inner hair cell stereocilia bundle. It is presumed that acoustical stimuli induce a fluid shear-driven motion between the tectorial membrane and the reticular lamina to deflect the bundle. It is hypothesized that ion channels are opened by molecular gates that sense tension in tip-links, which connect adjacent stepped rows of stereocilia. Yet almost nothing is known about how the fluid and bundle interact. Here we show using our microfluidics model how each row of stereocilia and their associated tip links and gates move in response to an acoustical input that induces an orbital motion of the reticular lamina. The model confirms the crucial role of the positioning of the tectorial membrane in hearing, and explains how this membrane amplifies and synchronizes the timing of peak tension in the tip links. Both stereocilia rotation and length change are needed for synchronization of peak tip link tension. Stereocilia length change occurs in response to accelerations perpendicular to the oscillatory fluid shear flow. Simulations indicate that nanovortices form between rows to facilitate diffusion of ions into channels, showing how nature has devised a way to solve the diffusive mixing problem that persists in engineered microfluidic devices.

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

    Science.gov (United States)

    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 the tunnel of Corti (ToC) in their course to innervate the OHCs. We show that this motion is present at physiologically relevant frequencies and remains at locations distal to the OHC excitation point. We interpret this fiber motion to be the result of oscillatory fluid flow in the ToC. We show, using a simple one-dimensional hydromechanical model of the ToC, that a fluid wave within the tunnel can travel without significant attenuation for distances larger than the wavelength of the cochlear traveling wave at its peak. This ToC fluid wave could interact with the cochlear traveling wave to amplify the motion of the basilar membrane. The ToC wave could also provide longitudinal coupling between adjacent sections of the basilar membrane, and such coupling may be critical for cochlear amplification. PMID:17277193

  17. 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.

  18. 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

  19. 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...... 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....

  20. 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

  1. Ag-NORs and the activity of human hair follicle cells Study%Ag-NORs与人头发毛囊细胞活性的研究

    Institute of Scientific and Technical Information of China (English)

    方峥; 唐文; 吴安花; 向玲丽; 叶合生; 胡琦; 杨粤军

    2013-01-01

    Objective Objective Study the correlation between the activities of men and women's hair folli-cle cells , white hair and black hair and the related Ag-NORS in the nuclear organizer region by means of male and female's hair follicle cell proliferation activity determination of nucleolus organizer regions of silver au-tophagy protein determination. Methods Collect the hair of fifty people of all ages and both sexes and extract the hair follicle cells from their hair, then put the nucleolus which is silver producer under the microscope to count the number of hair follicle cells of one thousand and one hundred people of all ages and both sexes and the num-ber of Ag-NOR. Results Young men's activities of hair follicle cells are no different than those of young women, while there is a big difference between the activities of hair follicle cells of the old people's white hair and those of young people. Conclusion Our experiment demonstrates that the number of AgNOR particles with high estima-tion value of cell activity.%目的:通过对男女性头发毛囊细胞增殖活性的核仁组成区嗜银蛋白(Ag-NORs)测定,定量分析男女头发、白发与黑发性的活性与核仁组成区相关嗜银蛋白(Ag-NORs)的关系。方法:分别收集50名男女老少性的头发,提取毛囊细胞,用核仁银染制片,显微镜下分别计数1100个男女老少及白发毛囊细胞核并统计Ag-NOR的数目。结果:年轻男女毛囊细胞活性相差不大,而老人白发与年轻人的头发毛囊细胞活性相差较大。结论:我们的实验说明AgNOR颗粒数目对细胞活性具有较高估测价值。

  2. Ag-NORs and the activity of human hair follicle cells Study%Ag-NORs与人头发毛囊细胞活性的研究

    Institute of Scientific and Technical Information of China (English)

    唐文; 吴安花; 向玲丽; 叶合生; 胡琦; 杨粤军

    2013-01-01

    Objective Study the correlation between the activities of men and women's hair follicle cells , white hair and black hair and the related Ag-NORS in the nuclear organizer region by means of male and fe-male's hair follicle cell proliferation activity determination of nucleolus organizer regions of silver autophagy pro-tein determination. Methods Collect the hair of fifty people of all ages and both sexes and extract the hair folli-cle cells from their hair, then put the nucleolus which is silver producer under the microscope to count the num-ber of hair follicle cells of one thousand and one hundred people of all ages and both sexes and the number of Ag-NOR. Results Young men's activities of hair follicle cells are no different than those of young women, while there is a big difference between the activities of hair follicle cells of the old people's white hair and those of young people. Conclusion Our experiment demonstrates that the number of AgNOR particles with high estimation value of cell activity.%  目的:通过对男女性头发毛囊细胞增殖活性的核仁组成区嗜银蛋白(Ag-NORs)测定,定量分析男女头发、白发与黑发性的活性与核仁组成区相关嗜银蛋白(Ag-NORs)的关系。方法:分别收集50名男女老少性的头发,提取毛囊细胞,用核仁银染制片,显微镜下分别计数1100个男女老少及白发毛囊细胞核并统计Ag-NOR的数目。结果:年轻男女毛囊细胞活性相差不大,而老人白发与年轻人的头发毛囊细胞活性相差较大。结论:AgNOR颗粒数目对细胞活性具有较高估测价值。

  3. 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.

  4. 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

    2015-11-26

    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.

  5. 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

  6. 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.

  7. 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...

  8. 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.

  9. 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

  10. Human placental extract exerts hair growth-promoting effects through the GSK-3β signaling pathway in human dermal papilla cells.

    Science.gov (United States)

    Kwon, Tae-Rin; Oh, Chang Taek; Choi, Eun Ja; Park, Hye Min; Han, Hae Jung; Ji, Hyi Jeong; Kim, Beom Joon

    2015-10-01

    Human placental extract (HPE) is widely used in Korea to relieve fatigue. However, its effects on human dermal papilla cells (hDPCs) remain unknown. In the present study, in an effort to develop novel therapies to promote hair growth, we screened HPE. We demonstrate that HPE has hair growth‑promoting activities and induces β‑catenin expression through the inhibition of glycogen synthase kinase‑3β (GSK‑3β) by phosphorylation in hDPCs. Treatment with HPE significantly increased the viability of the hDPCs in a concentration‑dependent manner, as shown by bromodeoxyuridine (BrdU) assay. HPE also significantly increased the alkaline phosphatase (ALP) expression levels. The increased β‑catenin levels and the inhibition of GSK‑3β (Ser9) by phosphorylation suggested that HPE promoted the hair-inductive capacity of hDPCs. We compared the effects of treatment with HPE alone and treatment with HPE in conjunction with minoxidil (MXD). We found that HPE plus MXD effectively inhibited GSK‑3β by phosphorylation (Ser9) in the hDPCs. Moreover, we demonstrated that HPE was effective in inducing root hair elongation in rat vibrissa hair follicles, and that treatment with HPE led to a delay in catagen progression. Overall, our findings suggest that HPE promotes hair growth and may thus provide the basis of a novel therapeutic strategy for the clinical treatment of hair loss. PMID:26311045

  11. 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

  12. 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...

  13. Protective role of L-ascorbic acid, N-acetylcysteine and apocynin on neomycin-induced hair cell loss in zebrafish.

    Science.gov (United States)

    Wu, Chia-Yen; Lee, Han-Jung; Liu, Chi-Fang; Korivi, Mallikarjuna; Chen, Hwei-Hsien; Chan, Ming-Huan

    2015-03-01

    Hair cells are highly sensitive to environmental insults and other therapeutic drugs. The adverse effects of drugs such as aminoglycosides can cause hair cell death and lead to hearing loss and imbalance. The objective of the present study was to evaluate the protective activity of L-ascorbic acid, N-acetylcysteine (NAC) and apocynin on neomycin-induced hair cell damage in zebrafish (Danio rerio) larvae at 5 days post fertilization (dpf). Results showed that the loss of hair cells within the neuromasts of the lateral lines after neomycin exposure was evidenced by a significantly lower number of neuromasts labeled with fluorescent dye FM1-43FX observed under a microscope. Co-administration with L-ascorbic acid, NAC and apocynin protected neomycin-induced hair cell loss within the neuromasts. Moreover, these three compounds reduced the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin, indicating that their antioxidant action is involved. In contrast, the neuromasts were labeled with specific fluorescent dye Texas-red conjugated with neomycin to detect neomycin uptake. Interestingly, the uptake of neomycin into hair cells was not influenced by these three antioxidant compounds. These data imply that prevention of hair cell damage against neomycin by L-ascorbic acid, NAC and apocynin might be associated with inhibition of excessive ROS production, but not related to modulating neomycin uptake. Our findings conclude that L-ascorbic acid, NAC and apocynin could be used as therapeutic drugs to protect aminoglycoside-induced listening impairment after further confirmatory studies.

  14. 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 ...

  15. 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...

  16. 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.

  17. NaHS Protects Cochlear Hair Cells from Gentamicin-Induced Ototoxicity by Inhibiting the Mitochondrial Apoptosis Pathway

    Science.gov (United States)

    Dong, Yaodong; Liu, Dongliang; Hu, Yue; Ma, Xiulan

    2015-01-01

    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. PMID:26295804

  18. 毛囊细胞移植法诱导毛囊的初步研究%Follicular cell implantation for induce hair follicle growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    谭挺; 胡志奇

    2009-01-01

    目的 构建一个可靠有效的移植毛囊细胞诱导毛发发育的模型,以治疗脱发.方法 取自愿捐献的成人头皮标本,联用显微分离与免疫磁珠法获得人毛囊干细胞;消化法获得毛乳头细胞.培养后混合植入裸鼠皮下,观察毛囊形成情况.结果 在裸鼠的皮肤切片中可以看到较为完整的毛囊结构形成.结论 毛囊细胞移植法可以在体内诱导出毛囊样结构,为将来治疗脱发奠定了基础.%Objective To establish a convenient and reliable method for inducing hair regeneration by follicular cell implantation for the treatment of alopecia. Methods The human hair follicle stem cells were separated and purified by micromanipulation and magnetic cell sorting, and human scalp dermal papilla cells were isolated by enzyme digestion. The two cells were mixed and implanted subcutaneously in nude mice to observe the regeneration of the hair follicles. Results Formation of intact hair follicle-like structures was observed in the skin sections of the recipient nude mice. Conclusion Follicular cell implantation can induce hair follicle-like structures in nude mice, which provides a means for efficient hair regeneration for treatment of hair loss.

  19. Effects of cinnarizine on calcium and pressure-dependent potassium currents in guinea pig vestibular hair cells.

    Science.gov (United States)

    Düwel, Philip; Haasler, Thorsten; Jüngling, Eberhard; Duong, Thien An; Westhofen, Martin; Lückhoff, Andreas

    2005-06-01

    In vestibular hair cells, K+ currents induced by rises in hydrostatic pressure have recently been demonstrated. These currents are inhibited by charybdotoxin, a blocker of Ca2+-dependent K+ channels. On the other hand, cinnarizine is a blocker of voltage-gated Ca2+ currents in hair cells and is used as a drug in conditions with vestibular vertigo. Our aim was to test in patch-clamp experiments (conventional whole-cell mode) whether cinnarizine, by reducing Ca2+ influx, inhibited Ca2+ and pressure-sensitive K+ currents in vestibular type-II hair cells of guinea pigs. A quantitatively similar inhibition of K+ currents was evoked by extracellular Ca2+ removal, cinnarizine (0.5 microM), and the L-type Ca2+ channel blocker nifedipine (3 microM). Cinnarizine abrogated increases of K+ currents induced by increases in the hydrostatic pressure (from 0.2 to 0.5 cm H2O). At a higher concentration (1 microM), cinnarizine elicited K+ current inhibitions larger than those elicited by Ca2+ removal. Moreover, it reduced K+ currents in the absence of Ca2+, in contrast to nifedipine. However, charybdotoxin abolished these effects of cinnarizine. We thus conclude that cinnarizine inhibits, by two mechanisms, pressure-induced currents that are sensitive to charybdotoxin and Ca2+. It reduces Ca2+ influx and exerts a Ca2+-independent inhibition, with a lower IC50 than that required for Ca2+ channel blockade. These two actions may importantly contribute to its therapeutic effects. PMID:16041595

  20. Artificial induction of Sox21 regulates sensory cell formation in the embryonic chicken inner ear.

    Directory of Open Access Journals (Sweden)

    Stephen D Freeman

    Full Text Available During embryonic development, hair cells and support cells in the sensory epithelia of the inner ear derive from progenitors that express Sox2, a member of the SoxB1 family of transcription factors. Sox2 is essential for sensory specification, but high levels of Sox2 expression appear to inhibit hair cell differentiation, suggesting that factors regulating Sox2 activity could be critical for both processes. Antagonistic interactions between SoxB1 and SoxB2 factors are known to regulate cell differentiation in neural tissue, which led us to investigate the potential roles of the SoxB2 member Sox21 during chicken inner ear development. Sox21 is normally expressed by sensory progenitors within vestibular and auditory regions of the early embryonic chicken inner ear. At later stages, Sox21 is differentially expressed in the vestibular and auditory organs. Sox21 is restricted to the support cell layer of the auditory epithelium, while it is enriched in the hair cell layer of the vestibular organs. To test Sox21 function, we used two temporally distinct gain-of-function approaches. Sustained over-expression of Sox21 from early developmental stages prevented prosensory specification, and abolished the formation of both hair cells and support cells. However, later induction of Sox21 expression at the time of hair cell formation in organotypic cultures of vestibular epithelia inhibited endogenous Sox2 expression and Notch activity, and biased progenitor cells towards a hair cell fate. Interestingly, Sox21 did not promote hair cell differentiation in the immature auditory epithelium, which fits with the expression of endogenous Sox21 within mature support cells in this tissue. These results suggest that interactions among endogenous SoxB family transcription factors may regulate sensory cell formation in the inner ear, but in a context-dependent manner.

  1. Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells

    NARCIS (Netherlands)

    Foijer, Floris; DiTommaso, Tia; Donati, Giacomo; Hautaviita, Katta; Xie, Stephanie Z.; Heath, Emma; Smyth, Ian; Watt, Fiona M.; Sorger, Peter K.; Bradley, Allan

    2013-01-01

    The spindle assembly checkpoint (SAC) ensures correct chromosome segregation during mitosis by preventing aneuploidy, an event that is detrimental to the fitness and survival of normal cells but oncogenic in tumor cells. Deletion of SAC genes is incompatible with early mouse development, and RNAi-me

  2. Generation of Induced Pluripotent Stem Cells from Hair Follicle Bulge Neural Crest Stem Cells

    NARCIS (Netherlands)

    Ma, Ming-San; Czepiel, Marcin; Krause, Tina; Schaefer, Karl-Herbert; Boddeke, Erik; Copray, Sjef

    2014-01-01

    Induced pluripotent stem cells (iPSCs) are promising candidates for the study of disease models as well as for tissue engineering purposes. Part of a strategy to develop safe reprogramming technique is reducing the number of exogenous reprogramming factors. Some cells types are more prone to reprogr

  3. Nutrition and hair: deficiencies and supplements.

    Science.gov (United States)

    Finner, Andreas M

    2013-01-01

    Hair follicle cells have a high turnover. A caloric deprivation or deficiency of several components, such as proteins, minerals, essential fatty acids, and vitamins, caused by inborn errors or reduced uptake, can lead to structural abnormalities, pigmentation changes, or hair loss, although exact data are often lacking. The diagnosis is established through a careful history, clinical examination of hair loss activity, and hair quality and confirmed through targeted laboratory tests. Examples of genetic hair disorders caused by reduced nutritional components are zinc deficiency in acrodermatitis enteropathica and copper deficiency in Menkes kinky hair syndrome.

  4. Determination of hair structure and shape.

    Science.gov (United States)

    Schlake, Thomas

    2007-04-01

    The hair follicle attracted significant attention as a model for the investigation of diverse biological problems. Whereas its morphology and the structure of the hair shaft are known in detail, the molecular biology of this miniorgan is significantly less characterised. Many efforts focussed on the development of the hair follicle and its stem cell reservoir; by contrast, the follicular product, the hair, which is interesting not only in terms of cosmetics was neglected. This review highlights our current knowledge of the control of hair structure and shape with emphasis on mouse hair follicle biology and discusses continuing problems.

  5. 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.

  6. Hair Removal

    DEFF Research Database (Denmark)

    Hædersdal, Merete

    2011-01-01

    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 ...... treatment procedures are evolving. Consumer-based treatments with portable home devices are rapidly evolving, and presently include low-level diode lasers and IPL devices....... 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...... systems. Evidence has been found for long-term hair removal efficacy beyond 6 months after repetitive treatments with alexandrite, diode, and long-pulse Nd:YAG lasers, whereas the current long-term evidence is sparse for IPL devices. Treatment parameters must be adjusted to patient skin type...

  7. 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

  8. FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular plate and regulate actin polymerization in vitro.

    Directory of Open Access Journals (Sweden)

    Huiren Cao

    Full Text Available Mammalian FCHSD1 and FCHSD2 are homologous proteins containing an amino-terminal F-BAR domain and two SH3 domains near their carboxyl-termini. We report here that FCHSD1 and FCHSD2 are expressed in mouse cochlear sensory hair cells. FCHSD1 mainly localizes to the cuticular plate, whereas FCHSD2 mainly localizes along the stereocilia in a punctuate pattern. Nervous Wreck (Nwk, the Drosophila ortholog of FCHSD1 and FCHSD2, has been shown to bind Wsp and play an important role in F-actin assembly. We show that, like its Drosophila counterpart, FCHSD2 interacts with WASP and N-WASP, the mammalian orthologs of Drosophila Wsp, and stimulates F-actin assembly in vitro. In contrast, FCHSD1 doesn't bind WASP or N-WASP, and can't stimulate F-actin assembly when tested in vitro. We found, however, that FCHSD1 binds via its F-BAR domain to the SH3 domain of Sorting Nexin 9 (SNX9, a well characterized BAR protein that has been shown to promote WASP-Arp2/3-dependent F-actin polymerization. FCHSD1 greatly enhances SNX9's WASP-Arp2/3-dependent F-actin polymerization activity. In hair cells, SNX9 was detected in the cuticular plate, where it colocalizes with FCHSD1. Our results suggest that FCHSD1 and FCHSD2 could modulate F-actin assembly or maintenance in hair cell stereocilia and cuticular plate.

  9. 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...

  10. 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.

  11. 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

  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. 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.

  14. 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)

  15. Dissection of the Mechanical Impedance Components of the Outer Hair Cell Using a Chloride-Channel Blocker

    Science.gov (United States)

    Harasztosi, Csaba; Gummer, Anthony W.

    2011-11-01

    The voltage-dependent chloride-channel blocker anthracene-9-carboxylic acid (9AC) has been found to reduce the imaginary but not the real part of the mechanical impedance of the organ of Corti, suggesting that the effective stiffness of outer hair cells (OHCs) is reduced by 9AC. To examine whether 9AC interacts directly with the motor protein prestin to reduce the membrane component of the impedance, the patch-clamp technique in whole-cell configuration was used to measure the nonlinear capacitance (NLC) of isolated OHCs and, as control, prestin-transfected human embryonic kidney 293 (HEK293) cells. Extracellular application of 9AC significantly reduced the NLC of both OHCs and HEK293 cells. Intracellular 9AC did not influence the blocking effect of the extracellular applied drug. These results suggest that 9AC interacts directly with prestin, reducing the effective stiffness of the motor, and that the interaction is extracellular.

  16. 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 ...

  17. 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 ...

  18. 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 ...

  19. Hair shape of curly hair.

    Science.gov (United States)

    Bernard, Bruno A

    2003-06-01

    The hair follicle is a unique composite organ, composed of epithelial and dermal compartments interacting with each other in a surprisingly autonomous way. This is a self-renewing organ that seems to be a true paradigm of epithelial and mesenchymal interactions. Each of the follicular compartments is endowed with a specific differentiation pathway under the control of an intricate network of growth factors, cytokines, and hormones. As observed for ethnic hairs, even the shape of the hair shaft is intrinsically programmed from the bulb.

  20. 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.