Sample records for hair cell losses

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

    PubMed

    Smith, Michael E

    2016-01-01

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

  2. Coping with cancer - hair loss

    MedlinePlus

    Cancer treatment - alopecia; Chemotherapy - hair loss; Radiation - hair loss ... Many chemotherapy drugs attack fast-growing cells. This is because cancer cells divide rapidly. Since the cells in hair ...

  3. Hair cell counts in a rat model of sound damage: Effects of tissue preparation & identification of regions of hair cell loss.

    PubMed

    Neal, Christopher; Kennon-McGill, Stefanie; Freemyer, Andrea; Shum, Axel; Staecker, Hinrich; Durham, Dianne

    2015-10-01

    Exposure to intense sound can damage or kill cochlear hair cells (HC). This loss of input typically manifests as noise induced hearing loss, but it can also be involved in the initiation of other auditory disorders such as tinnitus or hyperacusis. In this study we quantify changes in HC number following exposure to one of four sound damage paradigms. We exposed adult, anesthetized Long-Evans rats to a unilateral 16 kHz pure tone that varied in intensity (114 dB or 118 dB) and duration (1, 2, or 4 h) and sacrificed animals 2-4 weeks later. We compared two different methods of tissue preparation, plastic embedding/sectioning and whole mount dissection, for quantifying hair cell loss as a function of frequency. We found that the two methods of tissue preparation produced largely comparable cochleograms, with whole mount dissections allowing a more rapid evaluation of hair cell number. Both inner and outer hair cell loss was observed throughout the length of the cochlea irrespective of sound damage paradigm. Inner HC loss was either equal to or greater than outer HC loss. Increasing the duration of sound exposures resulted in more severe HC loss, which included all HC lesions observed in an analogous shorter duration exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK

    PubMed Central

    Hill, Kayla; Yuan, Hu; Wang, Xianren

    2016-01-01

    Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKα in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL. SIGNIFICANCE STATEMENT Our results demonstrate for the first time that the activation of AMP-activated protein kinase (AMPK) α in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKα1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy. PMID:27413159

  5. Hair Loss

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Hair Loss KidsHealth / For Teens / Hair Loss What's in ... after the problem that causes it is corrected. Hair Basics Hair is made of a kind of ...

  6. Hair Loss

    MedlinePlus

    Hair loss Overview Hair loss can affect just your scalp or your entire body. It can be the result of heredity, hormonal changes, medical conditions or medications. Anyone can experience hair loss, but it's more common in men. Baldness ...

  7. Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Mo; Wang, Qin; Zhu, Gang-Hua

    The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177–187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN{sup +/−} mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN{sup −/−} mice exhibited progressive sensorineural hearing loss as reflected bymore » auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN{sup −/−} mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene. - Highlights: • TPRN{sup −/−} mice were generated using TALEN technique. • TPRN{sup −/−} mice presented progressive hearing loss. • WT and TPRN{sup −/−} mice showed no difference in hair cell numbers. • TPRN{sup −/−} mice showed progressive degeneration of hair cell stereocilia.« less

  8. Ethanol extract of Piper longum L. attenuates gentamicin-induced hair cell loss in neonatal cochlea cultures.

    PubMed

    Du, Xiao Fei; Song, Jae-Jun; Hong, Seungug; Kim, Jihye

    2012-06-01

    Piper longum L. (PL), also as known as long pepper, a well-known spice and traditional medicine in Asia and Pacific islands, has been reported to exhibit wide spectrum activity including antioxidant activity. However, little information is available on its protective effect on gentamicin (GM) induced ototoxicity which is commonly regarded as being mediated by reactive oxygen species and reactive nitrogen species. This study was undertaken to investigate the protective effect of PL ethanol extract on gentamicin-induced hair cell loss in neonatal cochlea cultures. Cochlea cultures from postnatal day 2-3 mice were used for analysis of the protective effects of PL against gentamicin-induced hair cell loss by phalloidin staining. E. coil cultures were used to determine whether PL interferes with the antibiotic activity of GM. Nitric oxide (NO)-scavenging activity of PL was also measured in vitro. GM induced significant dose-dependent hair cell loss in cochlea cultures. However, without interfering with the antibiotic activity of GM, PL showed a significant and concentration-dependent protective effect against GM-induced hair cell loss, and hair cells retained their stereocilia well. In addition, PL expressed direct scavenging activity toward NO radical liberated within solution of sodium nitroprusside. These findings demonstrate the protective effect of PL on GM-induced hair cell loss in neonatal cochlea cultures, and suggest that it might be of therapeutic benefit for treatment of GM-induced ototoxicity.

  9. Hair Loss Myths.

    PubMed

    DiMarco, Gabriella; McMichael, Amy

    2017-07-01

    INTRODUCTION: Hair loss is a common complaint seen in dermatology clinics. From frustration and attempts at self-help, patients with hair loss may present to the dermatologist with false beliefs, or myths, about the causes of their condition and what treatments are effective.

    METHODS: We identified 12 common myths about hair loss, categorized as myths about minoxidil treatment, vitamin and mineral supplements, natural topical treatments, and hair care practices. We performed a PubMed search to find evidence to support or refute each myth.

    RESULTS: We found that there is little evidence to support many of these common hair loss myths. In some cases, randomized controlled trials have investigated the effects of particular therapies and point to the effectiveness of certain hair loss treatments.

    DISCUSSION: In many cases, there have not been sufficient randomized controlled trials to evaluate the effect of different therapies and hair care practices on hair loss. It is best to guide patients toward treatments with a long track record of efficacy and away from those where little is known scientifically.

    J Drugs Dermatol. 2017;16(7):690-694.

    .

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Mobilizing Transit-Amplifying Cell-Derived Ectopic Progenitors Prevents Hair Loss from Chemotherapy or Radiation Therapy.

    PubMed

    Huang, Wen-Yen; Lai, Shih-Fan; Chiu, Hsien-Yi; Chang, Michael; Plikus, Maksim V; Chan, Chih-Chieh; Chen, You-Tzung; Tsao, Po-Nien; Yang, Tsung-Lin; Lee, Hsuan-Shu; Chi, Peter; Lin, Sung-Jan

    2017-11-15

    Genotoxicity-induced hair loss from chemotherapy and radiotherapy is often encountered in cancer treatment, and there is a lack of effective treatment. In growing hair follicles (HF), quiescent stem cells (SC) are maintained in the bulge region, and hair bulbs at the base contain rapidly dividing, yet genotoxicity-sensitive transit-amplifying cells (TAC) that maintain hair growth. How genotoxicity-induced HF injury is repaired remains unclear. We report here that HFs mobilize ectopic progenitors from distinct TAC compartments for regeneration in adaptation to the severity of dystrophy induced by ionizing radiation (IR). Specifically, after low-dose IR, keratin 5 + basal hair bulb progenitors, rather than bulge SCs, were quickly activated to replenish matrix cells and regenerated all concentric layers of HFs, demonstrating their plasticity. After high-dose IR, when both matrix and hair bulb cells were depleted, the surviving outer root sheath cells rapidly acquired an SC-like state and fueled HF regeneration. Their progeny then homed back to SC niche and supported new cycles of HF growth. We also revealed that IR induced HF dystrophy and hair loss and suppressed WNT signaling in a p53- and dose-dependent manner. Augmenting WNT signaling attenuated the suppressive effect of p53 and enhanced ectopic progenitor proliferation after genotoxic injury, thereby preventing both IR- and cyclophosphamide-induced alopecia. Hence, targeted activation of TAC-derived progenitor cells, rather than quiescent bulge SCs, for anagen HF repair can be a potential approach to prevent hair loss from chemotherapy and radiotherapy. Cancer Res; 77(22); 6083-96. ©2017 AACR . ©2017 American Association for Cancer Research.

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

    PubMed Central

    Parker, Mark A.

    2011-01-01

    Purpose To provide an overview of the methodologies involved in the field of hair cell regeneration. First, a tutorial on the biotechnological foundations of this field will be provided in order to assist the reader in the comprehension and interpretation of the research involved in hair cell regeneration. Next, a review of stem cell and gene therapy will be presented and a critical appraisal of their application to hair cell regeneration will be provided. The methodologies used in these approaches will be highlighted. Method Narrative review of the fields of cellular, molecular, and developmental biology, tissue engineering, and stem cell and gene therapy using the PubMed database. Results The use of biotechnological approaches to the treatment of hearing loss, such as stem cell and gene therapy, has led to new methods of regenerating cochlear hair cells in mammals. Conclusions There have been incredible strides made in assembling important pieces of the puzzle that comprise hair cell regeneration. However, mammalian hair cell regeneration using stem cell and gene therapy are years if not decades away from being clinically feasible. If the goals of the biological approaches are met, these therapies may represent the future treatments for hearing loss. PMID:21386039

  13. Hair loss

    MedlinePlus

    ... that is applied to the scalp to stimulate hair growth. Other medicines, such as hormones, may be prescribed to decrease hair loss and promote hair growth. Drugs such as finasteride and dutasteride can be ...

  14. Female Pattern Hair Loss

    MedlinePlus

    ... Category: Share: Yes No, Keep Private Female Pattern Hair Loss Share | The most common type of hair loss seen in women is androgenetic alopecia, also ... men, it does not have to be complete hair loss. This is seen as hair thinning predominantly ...

  15. Managing Chemotherapy Side Effects: Hair Loss (Alopecia)

    MedlinePlus

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. Then I got used ... uncovered.” Questions other people have asked: Why does hair fall out? Chemotherapy can harm the cells that ...

  16. Hair loss in women.

    PubMed

    Tosti, A; Piraccini, B M; Sisti, A; Duque-Estrada, B

    2009-10-01

    Hair loss in women is a very common clinical complaint, and is usually associated with severe emotional distress. In this article, the authors review the most common clinical causes of hair loss in women, and emphasize the role of hormonal changes in the regulation of hair loss and hair growth.

  17. Help! It's Hair Loss!

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Hair Loss KidsHealth / For Kids / Hair Loss What's in ... is alopecia (say: al-uh-PEE-shuh). The Hair-y Story The hair on your head is ...

  18. Female Pattern Hair Loss

    MedlinePlus

    ... susceptible women, but is most commonly seen after menopause. In female pattern hair loss some excess loss of hair is noted, but ... all. Spironolactone pills help many women, especially whose hair loss starts before menopause but takes many months. Hormone replacement pills, such ...

  19. Return of Function after Hair Cell Regeneration

    PubMed Central

    Ryals, Brenda M.; Dent, Micheal L.; Dooling, Robert J.

    2012-01-01

    The ultimate goal of hair cell regeneration is to restore functional hearing. Because birds begin perceiving and producing song early in life, they provide a propitious model for studying not only whether regeneration of lost hair cells can return auditory sensitivity but also whether this regenerated periphery can restore complex auditory perception and production. They are the only animal where hair cell regeneration occurs naturally after hair cell loss and where the ability to correctly perceive and produce complex acoustic signals is critical to procreation and survival. The purpose of this review article is to survey the most recent literature on behavioral measures of auditory functional return in adult birds after hair cell regeneration. The first portion of the review summarizes the effect of ototoxic drug induced hair cell loss and regeneration on hearing loss and recovery for pure tones. The second portion reviews studies of complex, species-specific vocalization discrimination and recognition after hair cell regeneration. Finally, we discuss the relevance of temporary hearing loss and recovery through hair cell regeneration on complex call and song production. Hearing sensitivity is restored, except for the highest frequencies, after hair cell regeneration in birds, but there are enduring changes to complex auditory perception. These changes do not appear to provide any obstacle to future auditory or vocal learning. PMID:23202051

  20. Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

    PubMed Central

    Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

    2011-01-01

    Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

  1. TAUROURSODEOXYCHOLIC ACID PREVENTS HEARING LOSS AND HAIR CELL DEATH IN Cdh23erl/erl MICE

    PubMed Central

    HU, J.; XU, M.; YUAN, J.; LI, B.; Entenman, S.; YU, H.; ZHENG, Q.Y.

    2016-01-01

    Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cdh23 gene, Cdh23erl/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 Cdh23erl/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. PMID:26748055

  2. Side Effects: Hair Loss (Alopecia)

    Cancer.gov

    Hair loss, also called alopecia, is a side effect of cancer treatments, such as chemotherapy and radiation therapy. Learn how to cope with and manage hair loss. Listen to tips from others who have experienced hair loss.

  3. Protective effect of hexane and ethanol extract of piper longum L. On gentamicin-induced hair cell loss in neonatal cultures.

    PubMed

    Yadav, Mukesh Kumar; Choi, June; Song, Jae-Jun

    2014-03-01

    Gentamicin (GM) is a commonly used aminoglycoside antibiotic that generates free oxygen radicals within the inner ear, which can cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. Piper longum L. (PL) is a well-known spice and traditional medicine in Asia and Pacific islands, which has been reported to exhibit a wide spectrum of activity, including antioxidant activity. In this study, we evaluated the effect of hexane:ethanol (2:8) PL extract (subfraction of PL [SPL] extract) on GM-induced hair cell loss in basal, middle and apical regions in a neonatal cochlea cultures. The protective effects of SPL extract were measured by phalloidin staining of cultures from postnatal day 2-3 mice with GM-induced hair cell loss. The anti-apoptosis activity of SPL extract was measured using double labeling by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myosin-7a staining. The radical-scavenging activity of SPL extract was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. SPL extract at a concentration of 1 µg/mL significantly inhibited GM-induced hair cell loss at basal and middle region of cochlea, while 5 µg/mL was effective against apical region hair cell loss. The protective effect of SPL extract was concentration dependent and hair cells retained their stereocilia in explants treated with SPL extract prior to treatment with 0.3 mM GM. SPL extract decreased GM-induced apoptosis of hair cells as assessed by TUNEL staining. The outer hair and inner hair counts were not decreased in SPL extract treated groups in compare to GM treated explants. Additionally, SPL extract showed concentration dependent radical scavenging activity in a DPPH assay. An anti-apoptosis effect and potent radical scavenger activity of SPL extract protects from GM-induced hair cell loss at basal, middle and apical regions in neonatal cochlea cultures.

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

    PubMed

    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. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Selective inner hair cell loss in prematurity: a temporal bone study of infants from a neonatal intensive care unit.

    PubMed

    Amatuzzi, Monica; Liberman, M Charles; Northrop, Clarinda

    2011-10-01

    Premature birth is a well-known risk factor for sensorineural hearing loss in general and auditory neuropathy in particular. However, relatively little is known about the underlying causes, in part because there are so few relevant histopathological studies. Here, we report on the analysis of hair cell loss patterns in 54 temporal bones from premature infants and a control group of 46 bones from full-term infants, all of whom spent time in the neonatal intensive care unit at the Hospital de Niños in San Jose, Costa Rica, between 1977 and 1993. The prevalence of significant hair cell loss was higher in the preterm group than the full-term group (41% vs. 28%, respectively). The most striking finding was the frequency of selective inner hair cell loss, an extremely rare histopathological pattern, in the preterm vs. the full-term babies (27% vs. 3%, respectively). The findings suggest that a common cause of non-genetic auditory neuropathy is selective loss of inner hair cells rather than primary damage to the cochlear nerve.

  6. Stem cell plasticity enables hair regeneration following Lgr5+ cell loss.

    PubMed

    Hoeck, Joerg D; Biehs, Brian; Kurtova, Antonina V; Kljavin, Noelyn M; de Sousa E Melo, Felipe; Alicke, Bruno; Koeppen, Hartmut; Modrusan, Zora; Piskol, Robert; de Sauvage, Frederic J

    2017-06-01

    Under injury conditions, dedicated stem cell populations govern tissue regeneration. However, the molecular mechanisms that induce stem cell regeneration and enable plasticity are poorly understood. Here, we investigate stem cell recovery in the context of the hair follicle to understand how two molecularly distinct stem cell populations are integrated. Utilizing diphtheria-toxin-mediated cell ablation of Lgr5 + (leucine-rich repeat-containing G-protein-coupled receptor 5) stem cells, we show that killing of Lgr5 + cells in mice abrogates hair regeneration but this is reversible. During recovery, CD34 + (CD34 antigen) stem cells activate inflammatory response programs and start dividing. Pharmacological attenuation of inflammation inhibits CD34 + cell proliferation. Subsequently, the Wnt pathway controls the recovery of Lgr5 + cells and inhibition of Wnt signalling prevents Lgr5 + cell and hair germ recovery. Thus, our study uncovers a compensatory relationship between two stem cell populations and the underlying molecular mechanisms that enable hair follicle regeneration.

  7. Female pattern hair loss.

    PubMed

    Ioannides, Dimitrios; Lazaridou, Elizabeth

    2015-01-01

    Female pattern hair loss, or female pattern androgenetic alopecia, is a nonscarring alopecia with a multi-factorial etiology that mostly affects postmenopausal women and is characterized by a reduction in hair density over the crown and frontal scalp. The clinical picture is characterized by a diffuse rarefaction of scalp hair over the mid-frontal scalp and a more-or-less intact frontal hairline without any signs of inflammation or scarring. Although the disease poses only a cosmetic concern, it is chronic and may have a significant negative psychological impact on the affected person. The aim of treating female pattern hair loss is to reduce hair loss and, to a certain extent, succeed in promoting hair regrowth. Various treatment methods are available, but it remains unclear which are the most effective. Early initiation of treatment and the combination of various modalities seem to be more efficacious than monotherapy. © 2015 S. Karger AG, Basel.

  8. Hair loss in elderly women.

    PubMed

    Chen, WenChieh; Yang, Chao-Chun; Todorova, Antonia; Al Khuzaei, Safaa; Chiu, Hsien-Ching; Worret, Wolf-Ingo; Ring, Johannes

    2010-01-01

    Hair loss in elderly women has been becoming a major topic in the daily practice of dermatology. Aging of hair follicles seems to affect hair growth and pigmentation, the molecular mechanisms of which remain to be elucidated. Further senile changes in physiology and immunity may influence the onset and course of hair diseases. Some preexisting diseases such as androgenetic alopecia usually worsen after menopause, while others, like discoid lupus erythematosus, may attenuate. Hormone surveying, especially with regard to internal androgen-producing tumors, is indicated in postmenopausal women with androgenetic alopecia of sudden exacerbation or with unusual manifestation or other virilizing signs. The prevalence of alopecia totalis and alopecia universalis appears to be much lower in postmenopausal ages as compared to earlier onset. Acute or chronic telogen effluvium is not uncommonly superimposed on androgenetic alopecia. Trichotillomania shows a marked female predominance in the senile age group with a higher rate of psychopathology. Worldwide, tinea capitis has been increasingly observed in postmenopausal women. Frontal fibrosing alopecia, giant cell arteritis and erosive pustular dermatosis involve mainly elder women leading to scarring alopecia. Alopecia induced by tumor metastasis to the scalp must be considered in women with underlying neoplasms, especially breast cancer. Overall, hair loss in postmenopausal women is often multifactorial and warrants a close inspection.

  9. Reprogramming of single-cell derived mesenchymal stem cells into hair cell-like cells

    PubMed Central

    Lin, Zhaoyu; Perez, Philip; Sun, Zhenyu; Liu, Jan-Jan; Shin, June Ho; Hyrc, Krzysztof L.; Samways, Damien; Egan, Terry; Holley, Matthew C.; Bao, Jianxin

    2012-01-01

    Hypothesis Adult mesenchymal stem cells (MSCs) can be converted into hair cell-like cells by transdetermination. Background Given the fundamental role sensory hair cells play in sound detection and the irreversibility of their loss in mammals, much research has focused on developing methods to generate new hair cells as a means of treating permanent hearing loss. Although MSCs can differentiate into multiple cell lineages, no efficient means of reprogramming them into sensory hair cells exists. Earlier work has shown that the transcription factor Atoh1 is necessary for early development of hair cells, but it is not clear whether Atoh1 can be used to convert MSCs into hair cells. Methods Clonal MSC cell lines were established and reprogrammed into hair cell-like cells by a combination of protein transfer, adenoviral based gene transfer and co-culture with neurons. During transdetermination, inner ear molecular markers were analyzed by RT-PCR, and cell structures were examined by immunocytochemistry. Results Atoh1 overexpression in MSCs failed to convert MSCs into hair cell-like cells, suggesting that the ability of Atoh1 to induce hair cell differentiation is context dependent. Because Atoh1 overexpression successfully transforms VOT-E36 cells into hair cell-like cells, we modified the cell context of MSCs by performing a total protein transfer from VOT-E36 cells prior to overexpressing Atoh1. The modified MSCs were transformed into hair cell-like cells and attracted contacts from spiral ganglion neurons in a co-culture model. Conclusion We established a new procedure, consisting of VOT-E36 protein transfer, Atoh1 overexpression, and co-culture with spiral ganglion neurons, which can transform MSCs into hair cell-like cells. PMID:23111404

  10. Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: a pilot, double-blind, randomized, placebo-controlled trial.

    PubMed

    Oura, Hajimu; Iino, Masato; Nakazawa, Yosuke; Tajima, Masahiro; Ideta, Ritsuro; Nakaya, Yutaka; Arase, Seiji; Kishimoto, Jiro

    2008-12-01

    Adenosine upregulates the expression of vascular endothelial growth factor and fibroblast growth factor-7 in cultured dermal papilla cells. It has been shown that, in Japanese men, adenosine improves androgenetic alopecia due to the thickening of thin hair due to hair follicle miniaturization. To investigate the efficacy and safety of adenosine treatment to improve hair loss in women, 30 Japanese women with female pattern hair loss were recruited for this double-blind, randomized, placebo-controlled study. Volunteers used either 0.75% adenosine lotion or a placebo lotion topically twice daily for 12 months. Efficacy was evaluated by dermatologists and by investigators and in phototrichograms. As a result, adenosine was significantly superior to the placebo according to assessments by dermatologists and investigators and by self-assessments. Adenosine significantly increased the anagen hair growth rate and the thick hair rate. No side-effects were encountered during the trial. Adenosine improved hair loss in Japanese women by stimulating hair growth and by thickening hair shafts. Adenosine is useful for treating female pattern hair loss in women as well as androgenetic alopecia in men.

  11. Bmi1 regulates auditory hair cell survival by maintaining redox balance.

    PubMed

    Chen, Y; Li, L; Ni, W; Zhang, Y; Sun, S; Miao, D; Chai, R; Li, H

    2015-01-22

    Reactive oxygen species (ROS) accumulation are involved in noise- and ototoxic drug-induced hair cell loss, which is the major cause of hearing loss. Bmi1 is a member of the Polycomb protein family and has been reported to regulate mitochondrial function and ROS level in thymocytes and neurons. In this study, we reported the expression of Bmi1 in mouse cochlea and investigated the role of Bmi1 in hair cell survival. Bmi1 expressed in hair cells and supporting cells in mouse cochlea. Bmi1(-/-) mice displayed severe hearing loss and patched outer hair cell loss from postnatal day 22. Ototoxic drug-induced hair cells loss dramatically increased in Bmi1(-/-) mice compared with that in wild-type controls both in vivo and in vitro, indicating Bmi1(-/-) hair cells were significantly more sensitive to ototoxic drug-induced damage. Cleaved caspase-3 and TUNEL staining demonstrated that apoptosis was involved in the increased hair cell loss of Bmi1(-/-) mice. Aminophenyl fluorescein and MitoSOX Red staining showed the level of free radicals and mitochondrial ROS increased in Bmi1(-/-) hair cells due to the aggravated disequilibrium of antioxidant-prooxidant balance. Furthermore, the antioxidant N-acetylcysteine rescued Bmi1(-/-) hair cells from neomycin injury both in vitro and in vivo, suggesting that ROS accumulation was mainly responsible for the increased aminoglycosides sensitivity in Bmi1(-/-) hair cells. Our findings demonstrate that Bmi1 has an important role in hair cell survival by controlling redox balance and ROS level, thus suggesting that Bmi1 may work as a new therapeutic target for the prevention of hair cell death.

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

    PubMed

    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.

  13. Functional recovery in the avian ear after hair cell regeneration.

    PubMed

    Smolders, J W

    1999-01-01

    Trauma to the inner ear in birds, due to acoustic overstimulation or ototoxic aminoglycosides, can lead to hair cell loss which is followed by regeneration of new hair cells. These processes are paralleled by hearing loss followed by significant functional recovery. After acoustic trauma, functional recovery is rapid and nearly complete. The early and major part of functional recovery after sound trauma occurs before regenerated hair cells become functional. Even very intense sound trauma causes loss of only a proportion of the hair cell population, mainly so-called short hair cells residing on the abneural mobile part of the avian basilar membrane. Uncoupling of the tectorial membrane from the hair cells during sound overexposure may serve as a protection mechanism. The rapid functional recovery after sound trauma appears not to be associated with regeneration of the lost hair cells, but with repair processes involving the surviving hair cells. Small residual functional deficits after recovery are most likely associated with the missing upper fibrous layer of the tectorial membrane which fails to regenerate after sound trauma. After aminoglycoside trauma, functional recovery is slower and parallels the structural regeneration more closely. Aminoglycosides cause damage to both types of hair cells, starting at the basal (high frequency) part of the basilar papilla. However, functional hearing loss and recovery also occur at lower frequencies, associated with areas of the papilla where hair cells survive. Functional recovery in these low frequency areas is complete, whereas functional recovery in high frequency areas with complete hair cell loss is incomplete, despite regeneration of the hair cells. Permanent residual functional deficits remain. This indicates that in low frequency regions functional recovery after aminoglycosides involves repair of nonlethal injury to hair cells and/or hair cell-neural synapses. In the high frequency regions functional recovery

  14. Zebrafish hair cell mechanics and physiology through the lens of noise-induced hair cell death

    NASA Astrophysics Data System (ADS)

    Coffin, Allison B.; Xu, Jie; Uribe, Phillip M.

    2018-05-01

    Hair cells are exquisitely sensitive to auditory stimuli, but also to damage from a variety of sources including noise trauma and ototoxic drugs. Mammals cannot regenerate cochlear hair cells, while non-mammalian vertebrates exhibit robust regenerative capacity. Our research group uses the lateral line system of larval zebrafish to explore the mechanisms underlying hair cell damage, identify protective therapies, and determine molecular drivers of innate regeneration. The lateral line system contains externally located sensory organs called neuromasts, each composed of ˜8-20 hair cells. Lateral line hair cells are homologous to vertebrate inner ear hair cells and share similar susceptibility to ototoxic damage. In the last decade, the lateral line has emerged as a powerful model system for understanding hair cell death mechanisms and for identifying novel protective compounds. Here we demonstrate that the lateral line is a tractable model for noise-induced hair cell death. We have developed a novel noise damage system capable of inducing over 50% loss of lateral line hair cells, with hair cell death occurring in a dose- and time-dependent manner. Cell death is greatest 72 hours post-exposure. However, early signs of hair cell damage, including changes in membrane integrity and reduced mechanotransduction, are apparent within hours of noise exposure. These features, early signs of damage followed by delayed hair cell death, are consistent with mammalian data, suggesting that noise acts similarly on zebrafish and mammalian hair cells. In our future work we will use our new model system to investigate noise damage events in real time, and to develop protective therapies for future translational research.

  15. Paraquat initially damages cochlear support cells leading to anoikis-like hair cell death.

    PubMed

    Zhang, Jianhui; Sun, Hong; Salvi, Richard; Ding, Dalian

    2018-07-01

    Paraquat (PQ), one of the most widely used herbicides, is extremely dangerous because it generates the highly toxic superoxide radical. When paraquat was applied to cochlear organotypic cultures, it not only damaged the outer hair cells (OHCs) and inner hair cells (IHCs), but also caused dislocation of the hair cell rows. We hypothesized that the dislocation arose from damage to the support cells (SCs) that anchors hair cells within the epithelium. To test this hypothesis, rat postnatal cochlear cultures were treated with PQ. Shortly after PQ treatment, the rows of OHCs separated from one another and migrated radially away from IHCs suggesting loss of cell-cell adhesion that hold the hair cells in proper alignment. Hair cells dislocation was associated with extensive loss of SCs in the organ of Corti, loss of tympanic border cells (TBCs) beneath the basilar membrane, the early appearance of superoxide staining and caspase-8 labeling in SCs below the OHCs and disintegration of E-cadherin and β-catenin in the organ of Corti. Damage to the TBCs and SCs occurred prior to loss of OHC or IHC loss suggesting a form of detachment-induced apoptosis referred to as anoikis. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Concise Review: Regeneration in Mammalian Cochlea Hair Cells: Help from Supporting Cells Transdifferentiation.

    PubMed

    Franco, Bénédicte; Malgrange, Brigitte

    2017-03-01

    It is commonly assumed that mammalian cochlear cells do not regenerate. Therefore, if hair cells are lost following an injury, no recovery could occur. However, during the first postnatal week, mice harbor some progenitor cells that retain the ability to give rise to new hair cells. These progenitor cells are in fact supporting cells. Upon hair cells loss, those cells are able to generate new hair cells both by direct transdifferentiation or following cell cycle re-entry and differentiation. However, this property of supporting cells is progressively lost after birth. Here, we review the molecular mechanisms that are involved in mammalian hair cell development and regeneration. Manipulating pathways used during development constitute good candidates for inducing hair cell regeneration after injury. Despite these promising studies, there is still no evidence for a recovery following hair cells loss in adult mammals. Stem Cells 2017;35:551-556. © 2017 AlphaMed Press.

  17. Serenoa repens extracts promote hair regeneration and repair of hair loss mouse models by activating TGF-β and mitochondrial signaling pathway.

    PubMed

    Zhu, H-L; Gao, Y-H; Yang, J-Q; Li, J-B; Gao, J

    2018-06-01

    Plenty of plant extracts have been used for treating hair loss. This study aims to investigate the effects of liposterolic extracts of Serenoa repens (LSESr) on hair cell growth and regeneration of hair, and clarify the associated mechanisms. Human keratinocyte cells (HACAT) were cultured, incubated with dihydrotestosterone (DHT) and treated with LSESr. Cell viability was examined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) assay. Hair loss C57BL/6 mouse model was established by inducing with DHT. Hair growth, density, and thickness were evaluated. Back skin samples were collected and stained with hematoxylin and eosin (HE) assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), cleaved caspase 3 and transforming growth factor β2 (TGF-β2) were examined using Western blot assay. LSESr treatment significantly increased HACAT cell viabilities compared to DHT-only treated cells (p<0.05). LSESr treatment post injection of DHT significantly converted skin color from pink to gray and increased hair density, weight and thickness compared to DHT-only treated mice (p<0.05). LSESr treatment significantly triggered follicle growth and decreased inflammatory response. LSESr treatment significantly decreased TGF-β2 and cleaved caspase 3 expression of hair loss mouse models compared to that of DHT treated mice (p<0.05). LSESr treatment significantly enhanced Bcl-2 expression and reduced Bax expression compared to that of DHT treated mice (p<0.05). Meanwhile, effects of LSESr were substantial even achieving to the potential of finasteride. LSESr promoted the hair regeneration and repair of hair loss mouse models by activating TGF-β signaling and mitochondrial signaling pathway.

  18. Female pattern hair loss: Current treatment concepts

    PubMed Central

    Dinh, Quan Q; Sinclair, Rodney

    2007-01-01

    Fewer than 45% of women go through life with a full head of hair. Female pattern hair loss is the commonest cause of hair loss in women and prevalence increases with advancing age. Affected women may experience psychological distress and impaired social functioning. In most cases the diagnosis can be made clinically and the condition treated medically. While many women using oral antiandrogens and topical minoxidil will regrow some hair, early diagnosis and initiation of treatment is desirable as these treatments are more effective at arresting progression of hair loss than stimulating regrowth. Adjunctive nonpharmacological treatment modalities such as counseling, cosmetic camouflage and hair transplantation are important measures for some patients. The histology of female pattern hair loss is identical to that of male androgenetic alopecia. While the clinical pattern of the hair loss differs between men, the response to oral antiandrogens suggests that female pattern hair loss is an androgen dependant condition, at least in the majority of cases. Female pattern hair loss is a chronic progressive condition. All treatments need to be continued to maintain the effect. An initial therapeutic response often takes 12 or even 24 months. Given this delay, monitoring for treatment effect through clinical photography or standardized clinical severity scales is helpful. PMID:18044135

  19. Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2/Ctl2.

    PubMed

    Kommareddi, Pavan; Nair, Thankam; Kakaraparthi, Bala Naveen; Galano, Maria M; Miller, Danielle; Laczkovich, Irina; Thomas, Trey; Lu, Lillian; Rule, Kelli; Kabara, Lisa; Kanicki, Ariane; Hughes, Elizabeth D; Jones, Julie M; Hoenerhoff, Mark; Fisher, Susan G; Altschuler, Richard A; Dolan, David; Kohrman, David C; Saunders, Thomas L; Carey, Thomas E

    2015-12-01

    SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2(Δ/Δ)resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven(N7) (99 % FVB). Slc44a2(Δ/Δ) mice produced abnormally spliced Slc44a2 transcripts that contain a frame shift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2(Δ/Δ) mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age,Slc44a2(Δ/Δ) mice exhibited hearing loss at 32 kHz,but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2(+/+) and heterozygous +/Slc44a2Δ mice. After 6 months of age, Slc44a2(Δ/Δ) mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2(Δ) mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2(Δ/Δ) mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing.

  20. No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

    PubMed Central

    2010-01-01

    Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs) is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family. PMID:20637089

  1. Investigation of hair dye deposition, hair color loss, and hair damage during multiple oxidative dyeing and shampooing cycles.

    PubMed

    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.

  2. Managing hair loss in midlife women.

    PubMed

    Mirmirani, Paradi

    2013-02-01

    Hair is considered one of the most defining aspects of human appearance. Hair loss, or alopecia in women is often met with significant emotional distress and anxiety. In midlife, women may encounter various hormonal and age-related physiologic changes that can lead to alterations in hair texture and growth. The most significant hormonal alteration is the onset of menopause in which there is a cessation of ovarian estrogen production. This decrease in estrogen is known to have deleterious effects on the skin and cutaneous appendages. As our understanding of the molecular and hormonal controls on the hair follicle has grown, there has been increased interest in the various modulators of hair growth, including the potential role of estrogen. Further study of hair changes in midlife women provides an important opportunity for identification of the complex regulation of hair growth as well as identification of treatment targets that may specifically benefit women. In this review, management of hair loss in midlife women is discussed with a focus on three most commonly encountered clinical conditions: female pattern hair loss, hair shaft alterations due to hair care, and telogen effluvium. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Stress and Hair Loss: Are They Related?

    MedlinePlus

    Healthy Lifestyle Stress management Can stress cause hair loss? Answers from Daniel K. Hall-Flavin, M.D. Yes, stress and hair loss ... Original article: http://www.mayoclinic.org/healthy-lifestyle/stress-management/expert-answers/stress-and-hair-loss/faq-20057820 . ...

  4. Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea

    PubMed Central

    Taylor, Ruth R.; Jagger, Daniel J.; Forge, Andrew

    2012-01-01

    Background Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. Methodology/Principal Findings Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca's, suggesting genetic background influences the rate of re-organisation. Conclusions/Significance The lack of dedifferentiation amongst supporting cells and their replacement by cells from the outer side of the organ of Corti are factors that may need to be considered in any attempt to promote endogenous hair cell regeneration. The variability of the cellular environment along an individual cochlea arising from patch-like generation of flat epithelium, and the possible variability between individuals resulting from genetic

  5. Transitory endolymph leakage induced hearing loss and tinnitus: depolarization, biphasic shortening and loss of electromotility of outer hair cells

    NASA Technical Reports Server (NTRS)

    Zenner, H. P.; Reuter, G.; Zimmermann, U.; Gitter, A. H.; Fermin, C.; LePage, E. L.

    1994-01-01

    There are types of deafness and tinnitus in which ruptures or massive changes in the ionic permeability of the membranes lining the endolymphatic space [e.g., of the reticular lamina (RL)] are believed to allow potassium-rich endolymph to deluge the low [K+] perilymphatic fluid (e.g., in the small spaces of Nuel). This would result in a K+ intoxication of sensory and neural structures. Acute attacks of Meniere's disease have been suggested to be an important example for this event. The present study investigated the effects of transiently elevated [K+] due to the addition of artificial endolymph to the basolateral cell surface of outer hair cells (OHC) in replicating endolymph-induced K+ intoxication of the perilymph in the small spaces of Nuel. The influence of K+ intoxication of the basolateral OHC cell surface on the transduction was then examined. Intoxication resulted in an inhibition of the physiological repolarizing K+ efflux from hair cells. This induced unwanted depolarizations of the hair cells, interfering with mechanoelectrical transduction. A pathological longitudinal OHC shortening was also found, with subsequent compression of the organ of Corti possibly influencing the micromechanics of the mechanically active OHC. Both micromechanical and electrophysiological alterations are proposed to contribute to endolymph leakage induced attacks of deafness and possibly also to tinnitus. Moreover, repeated or long-lasting K+ intoxications of OHC resulted in a chronic and complete loss of OHC motility. This is suggested to be a pathophysiological basis in some patients with chronic hearing loss resulting from Meniere's syndrome.

  6. Age-related changes in auditory nerve-inner hair cell connections, hair cell numbers, auditory brain stem response and gap detection in UM-HET4 mice.

    PubMed

    Altschuler, R A; Dolan, D F; Halsey, K; Kanicki, A; Deng, N; Martin, C; Eberle, J; Kohrman, D C; Miller, R A; Schacht, J

    2015-04-30

    This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in gap detection (GD), the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons (SGN), and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in the auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell-auditory nerve connections and a significant reduction in GD. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in GD, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of GD or with the loss of connections, consistent with independent pathological mechanisms. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Lgr5-Positive Supporting Cells Generate New Hair Cells in the Postnatal Cochlea

    PubMed Central

    Bramhall, Naomi F.; Shi, Fuxin; Arnold, Katrin; Hochedlinger, Konrad; Edge, Albert S.B.

    2014-01-01

    Summary The prevalence of hearing loss after damage to the mammalian cochlea has been thought to be due to a lack of spontaneous regeneration of hair cells, the primary receptor cells for sound. Here, we show that supporting cells, which surround hair cells in the normal cochlear epithelium, differentiate into new hair cells in the neonatal mouse following ototoxic damage. Using lineage tracing, we show that new hair cells, predominantly outer hair cells, arise from Lgr5-expressing inner pillar and third Deiters cells and that new hair cell generation is increased by pharmacological inhibition of Notch. These data suggest that the neonatal mammalian cochlea has some capacity for hair cell regeneration following damage alone and that Lgr5-positive cells act as hair cell progenitors in the cochlea. PMID:24672754

  8. The potential use of low-frequency tones to locate regions of outer hair cell loss.

    PubMed

    Kamerer, Aryn M; Diaz, Francisco J; Peppi, Marcello; Chertoff, Mark E

    2016-12-01

    Current methods used to diagnose cochlear hearing loss are limited in their ability to determine the location and extent of anatomical damage to various cochlear structures. In previous experiments, we have used the electrical potential recorded at the round window -the cochlear response (CR) -to predict the location of damage to outer hair cells in the gerbil. In a follow-up experiment, we applied 10 mM ouabain to the round window niche to reduce neural activity in order to quantify the neural contribution to the CR. We concluded that a significant proportion of the CR to a 762 Hz tone originated from phase-locking activity of basal auditory nerve fibers, which could have contaminated our conclusions regarding outer hair cell health. However, at such high concentrations, ouabain may have also affected the responses from outer hair cells, exaggerating the effect we attributed to the auditory nerve. In this study, we lowered the concentration of ouabain to 1 mM and determined the physiologic effects on outer hair cells using distortion-product otoacoustic emissions. As well as quantifying the effects of 1 mM ouabain on the auditory nerve and outer hair cells, we attempted to reduce the neural contribution to the CR by using near-infrasonic stimulus frequencies of 45 and 85 Hz, and hypothesized that these low-frequency stimuli would generate a cumulative amplitude function (CAF) that could reflect damage to hair cells in the apex more accurately than the 762 stimuli. One hour after application of 1 mM ouabain, CR amplitudes significantly increased, but remained unchanged in the presence of high-pass filtered noise conditions, suggesting that basal auditory nerve fibers have a limited contribution to the CR at such low frequencies. Published by Elsevier B.V.

  9. Hair loss and hyperprolactinemia in women

    PubMed Central

    2012-01-01

    In the literature of the past 30 years there are only some publications concerned with hair loss and hyperprolactinemia in women. Therefore, the relevance of hyperprolactinemia was evaluated in 40 women with diffuse alopecia. Hair loss was assessed by clinical appearance and the pluck trichogram. 82.5% of the female patients had diffuse hair loss and 17.5% had androgenetic alopecia. The highest prolactin values measured were 1390 ng/ml and 255 ng/ml. Six patients had values between 150–80.4 ng/ml and 10 between 79.1–51.7 ng/ml. All others had prolactin values below 50 ng/ml. Fifteen untreated patients with elevated prolactin levels could be followed up. Without any prolactin-inhibiting drugs, reductions and normalizations beside moderate fluctuations could be detected. Thyroid-specific diagnostics showed in 95% of the patients a normal thyroid function. 2.5% had a slight hyperthyreoidism and 2.5% had a slight hypothyreoidism. No female patient had clinical signs of androgenization and the determined androgens testosterone, androstendione and dihydroepiandrostendione were in the normal range. According to these results, moderate elevated prolactin levels in association with diffuse or androgenetic hair loss can be neglected as causative for the hair loss, because there is no evidence that they have an influence to the pattern, the extent or the duration of the hair loss. These results are supported by investigations of other authors who described only in high doses of prolactin an inhibiting effect on human hair follicles in vitro. Nevertheless, moderate constantly elevated prolactin levels should induce further diagnostics to exclude a prolactin-producing tumor of the pituitary gland. PMID:22870355

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

    PubMed

    Lee, Sang Goo; Huang, Mingqian; 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.

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

    PubMed Central

    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

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

    NASA Technical Reports Server (NTRS)

    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.

  13. Mouse models for human hair loss disorders

    PubMed Central

    Porter, Rebecca M

    2003-01-01

    The outer surface of the hand, limb and body is covered by the epidermis, which is elaborated into a number of specialized appendages, evolved not only to protect and reinforce the skin but also for social signalling. The most prominent of these appendages is the hair follicle. Hair follicles are remarkable because of their prolific growth characteristics and their complexity of differentiation. After initial embryonic morphogenesis, the hair follicle undergoes repeated cycles of regression and regeneration throughout the lifetime of the organism. Studies of mouse mutants with hair loss phenotypes have suggested that the mechanisms controlling the hair cycle probably involve many of the major signalling molecules used elsewhere in development, although the complete pathway of hair follicle growth control is not yet understood. Mouse studies have also led to the discovery of genes underlying several human disorders. Future studies of mouse hair-loss mutants are likely to benefit the understanding of human hair loss as well as increasing our knowledge of mechanisms controlling morphogenesis and tumorigenesis. PMID:12587927

  14. Sensory hair cell development and regeneration: similarities and differences

    PubMed Central

    Atkinson, Patrick J.; Huarcaya Najarro, Elvis; Sayyid, Zahra N.; Cheng, Alan G.

    2015-01-01

    Sensory hair cells are mechanoreceptors of the auditory and vestibular systems and are crucial for hearing and balance. In adult mammals, auditory hair cells are unable to regenerate, and damage to these cells results in permanent hearing loss. By contrast, hair cells in the chick cochlea and the zebrafish lateral line are able to regenerate, prompting studies into the signaling pathways, morphogen gradients and transcription factors that regulate hair cell development and regeneration in various species. Here, we review these findings and discuss how various signaling pathways and factors function to modulate sensory hair cell development and regeneration. By comparing and contrasting development and regeneration, we also highlight the utility and limitations of using defined developmental cues to drive mammalian hair cell regeneration. PMID:25922522

  15. A review of gene delivery and stem cell based therapies for regenerating inner ear hair cells.

    PubMed

    Devarajan, Keerthana; Staecker, Hinrich; Detamore, Michael S

    2011-09-13

    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.

  16. Conservation of hearing and protection of auditory hair cells against trauma-induced losses by local dexamethasone therapy: molecular and genetic mechanisms.

    PubMed

    Van De Water, Thomas R; Abi Hachem, Ralph N; Dinh, Christine T; Bas, Esperanza; Haake, Scott M; Hoosien, Gia; Vivero, Richard; Chan, Sherry; He, Jao; Eshraghi, Adrien A; Angeli, Simon I; Telischi, Fred F; Balkany, Thomas J

    2010-06-01

    Dexamethasone (DXM) protects hearing against trauma-induced loss. in vivo: A guinea pig model of electrode induced trauma (EIT)-induced hearing loss was used to locally deliver dexamethasone. In vitro: TNF-α-challenged organ of Corti explants treated with DXM or polymer-eluted DXM +/- PI3K/Akt/PkB/NFkB inhibitors were used for hair cells count and gene expression studies. in vivo: local DXM treatment of EIT-animals prevents trauma-induced loss of ABR thresholds that occurs in EIT-animals and EIT-animals treated with the carrier solution (i.e., AP), and prevented loss of auditory hair cells. In vitro: DXM and polymer-eluted DXM were equally effective in protecting hair cells from ototoxic levels of TNF-α Inhibitor treated explants demonstrated that DXM treatment requires both Akt/PKB and NFkB signalling for otoprotection. DXM treatment of explants showed up regulation of anti-apoptosis related genes (i.e., Bcl-2, Bcl-xl) and down regulation of pro-apoptosis related genes (i.e., Bax, TNFR-1). DXM exert its otoprotective action by activation of cell signal molecules (e.g., NFkB) that alter the expression of anti- and pro-apoptosis genes.

  17. Hair Loss (Alopecia)

    MedlinePlus

    ... Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions Cleft & Craniofacial Developmental ... with certain abnormalities of the nails and the teeth. Later in childhood, hair loss may be due ...

  18. Pejvakin, a Candidate Stereociliary Rootlet Protein, Regulates Hair Cell Function in a Cell-Autonomous Manner

    PubMed Central

    Kazmierczak, Piotr; Harris, Suzan L.; Shah, Prahar; Puel, Jean-Luc; Lenoir, Marc

    2017-01-01

    Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and colocalizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations. Hair cells of pejvakin-deficient mice develop normal rootlets, but hair bundle morphology and mechanotransduction are affected before the onset of hearing. Some mechanotransducing shorter row stereocilia are missing, whereas the remaining ones exhibit overextended tips and a greater variability in height and width. Unlike previous studies of Pjvk alleles with neuronal dysfunction, our findings reveal a cell-autonomous role of pejvakin in maintaining stereocilia architecture that is critical for hair cell function. SIGNIFICANCE STATEMENT Two missense mutations in the Pejvakin (PJVK or DFNB59) gene were first identified in patients with audiological hallmarks of auditory neuropathy spectrum disorder, whereas all other PJVK alleles cause hearing loss of cochlear origin. These findings suggest that complex pathogenetic mechanisms underlie human deafness DFNB59. In contrast to recent studies, we demonstrate that pejvakin in auditory neurons is not essential for normal hearing in mice. Moreover, pejvakin localizes to stereociliary rootlets in hair cells and is required for stereocilia maintenance and mechanosensory function of the hair bundle. Delineating the site of the lesion and the mechanisms underlying DFNB59 will allow clinicians to predict the efficacy of different therapeutic approaches, such as determining compatibility for cochlear implants. PMID:28209736

  19. Sensory hair cell death and regeneration in fishes

    PubMed Central

    Monroe, Jerry D.; Rajadinakaran, Gopinath; Smith, Michael E.

    2015-01-01

    Sensory hair cells are specialized mechanotransductive receptors required for hearing and vestibular function. Loss of hair cells in humans and other mammals is permanent and causes reduced hearing and balance. In the early 1980’s, it was shown that hair cells continue to be added to the inner ear sensory epithelia in cartilaginous and bony fishes. Soon thereafter, hair cell regeneration was documented in the chick cochlea following acoustic trauma. Since then, research using chick and other avian models has led to great insights into hair cell death and regeneration. However, with the rise of the zebrafish as a model organism for studying disease and developmental processes, there has been an increased interest in studying sensory hair cell death and regeneration in its lateral line and inner ears. Advances derived from studies in zebrafish and other fish species include understanding the effect of ototoxins on hair cells and finding otoprotectants to mitigate ototoxin damage, the role of cellular proliferation vs. direct transdifferentiation during hair cell regeneration, and elucidating cellular pathways involved in the regeneration process. This review will summarize research on hair cell death and regeneration using fish models, indicate the potential strengths and weaknesses of these models, and discuss several emerging areas of future studies. PMID:25954154

  20. Cell proliferation during hair cell regeneration induced by Math1 in vestibular epithelia in vitro

    PubMed Central

    Huang, Yi-bo; Ma, Rui; Yang, Juan-mei; Han, Zhao; Cong, Ning; Gao, Zhen; Ren, Dongdong; Wang, Jing; Chi, Fang-lu

    2018-01-01

    Hair cell regeneration is the fundamental method of correcting hearing loss and balance disorders caused by hair cell damage or loss. How to promote hair cell regeneration is a hot focus in current research. In mammals, cochlear hair cells cannot be regenerated and few vestibular hair cells can be renewed through spontaneous regeneration. However, Math1 gene transfer allows a few inner ear cells to be transformed into hair cells in vitro or in vivo. Hair cells can be renewed through two possible means in birds: supporting cell differentiation and transdifferentiation with or without cell division. Hair cell regeneration is strongly associated with cell proliferation. Therefore, this study explored the relationship between Math1-induced vestibular hair cell regeneration and cell division in mammals. The mouse vestibule was isolated to harvest vestibular epithelial cells. Ad-Math1-enhanced green fluorescent protein (EGFP) was used to track cell division during hair cell transformation. 5-Bromo-2′-deoxyuridine (BrdU) was added to track cell proliferation at various time points. Immunocytochemistry was utilized to determine cell differentiation and proliferation. Results demonstrated that when epithelial cells were in a higher proliferative stage, more of these cells differentiated into hair cells by Math1 gene transfer. However, in the low proliferation stage, no BrdU-positive cells were seen after Math1 gene transfer. Cell division always occurred before Math1 transfection but not during or after Math1 transfection, when cells were labeled with BrdU before and after Ad-Math1-EGFP transfection. These results confirm that vestibular epithelial cells with high proliferative potential can differentiate into new hair cells by Math1 gene transfer, but this process is independent of cell proliferation. PMID:29623936

  1. Gender differences in scalp hair growth rates are maintained but reduced in pattern hair loss compared to controls.

    PubMed

    Van Neste, D J J; Rushton, D H

    2016-08-01

    Hair loss is related to follicular density, programmed regrowth and hair productivity. The dissatisfaction with hair growth in patients experiencing hair loss might be due to slower linear hair growth rate (LHGR). LHGR and hair diameter was evaluated in Caucasian controls and patients with patterned hair loss employing the validated non-invasive, contrast-enhanced-phototrichogram with exogen collection. We evaluated 59,765 anagen hairs (controls 24,609, patients 35,156) and found thinner hairs grew slower than thicker hairs. LHGR in normal women was generally higher than in normal men. LHGR correlates with hair diameter (P < 0.006) and global thinning is associated with slower growth rates. Compared with hair of equal thickness in controls, subjects affected with patterned hair loss showed reduced hair growth rates, an observation found in both male and female patients. Males with pattern hair loss showed further reduction in growth rates as clinical severity worsened. However, sample size limitations prevented statistical evaluation of LHGR in severely affected females. Caucasian ethnicity. In pattern hair loss, LHGR significantly contributes to the apparent decrease in hair volume in affected areas. In early onset, LHRG might have a prognostic value in females but not in males. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Regeneration of hair cells in the mammalian vestibular system.

    PubMed

    Li, Wenyan; You, Dan; Chen, Yan; Chai, Renjie; Li, Huawei

    2016-06-01

    Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss. Moreover, recently many strategies have been developed to promote the hair cell regeneration and subsequent functional recovery of the vestibular system, including manipulating the Wnt, Notch and Atoh1. This article provides an overview of the recent advances in hair cell regeneration in mammalian vestibular epithelia. Furthermore, this review highlights the current limitations of hair cell regeneration and provides the possible solutions to regenerate functional hair cells and to partially restore vestibular function.

  3. Feathers and fins: non-mammalian models for hair cell regeneration.

    PubMed

    Brignull, Heather R; Raible, David W; Stone, Jennifer S

    2009-06-24

    Death of mechanosensory cells in the inner ear results in two profound disabilities: hearing loss and balance disorders. Although mammals lack the capacity to regenerate hair cells, recent studies in mice and other rodents have offered valuable insight into strategies for stimulating hair cell regeneration in mammals. Investigations of model organisms that retain the ability to form new hair cells after embryogenesis, such as fish and birds, are equally important and have provided clues as to the cellular and molecular mechanisms that may block hair cell regeneration in mammals. Here, we summarize studies on hair cell regeneration in the chicken and the zebrafish, discuss specific advantages of each model, and propose future directions for the use of non-mammalian models in understanding hair cell regeneration.

  4. Hair loss in women.

    PubMed

    Camacho-Martínez, Francisco M

    2009-03-01

    Female pattern hair loss (FPHL) is a clinical problem that is becoming more common in women. Female alopecia with androgen increase is called female androgenetic alopecia (FAGA) and without androgen increase is called female pattern hair loss. The clinical picture of typical FAGA begins with a specific "diffuse loss of hair from the parietal or frontovertical areas with an intact frontal hairline." Ludwig called this process "rarefaction." In Ludwig's classification of hair loss in women, progressive type of FAGA, 3 patterns were described: grade I or minimal, grade II or moderate, and grade III or severe. Ludwig also described female androgenetic alopecia with male pattern (FAGA.M) that should be subclassified according to Ebling's or Hamilton-Norwood's classification. FAGA.M may be present in 4 conditions: persistent adrenarche syndrome, alopecia caused by an adrenal or an ovarian tumor, posthysterectomy, and as an involutive alopecia. A more recent classification (Olsen's classification of FPHL) proposes 2 types: early- and late-onset with or without excess of androgens in each. The diagnosis of FPHL is made by clinical history, clinical examination, wash test, dermoscopy, trichoscan, trichograms and laboratory test, especially androgenic determinations. Topical treatment of FPHL is with minoxidil, 2-5% twice daily. When FPHL is associated with high levels of androgens, systemic antiandrogenic therapy is needed. Persistent adrenarche syndrome (adrenal SAHA) and alopecia of adrenal hyperandrogenism is treated with adrenal suppression and antiandrogens. Adrenal suppression is achieved with glucocorticosteroids. Antiandrogens therapy includes cyproterone acetate, drospirenone, spironolactone, flutamide, and finasteride. Excess release of ovarian androgens (ovarian SAHA) and alopecia of ovarian hyperandrogenism is treated with ovarian suppression and antiandrogens. Ovarian suppression includes the use of contraceptives containing an estrogen, ethinylestradiol, and a

  5. Deletion of SLC19A2, the high affinity thiamine transporter, causes selective inner hair cell loss and an auditory neuropathy phenotype.

    PubMed

    Liberman, M C; Tartaglini, E; Fleming, J C; Neufeld, E J

    2006-09-01

    Mutations in the gene coding for the high-affinity thiamine transporter Slc19a2 underlie the clinical syndrome known as thiamine-responsive megaloblastic anemia (TRMA) characterized by anemia, diabetes, and sensorineural hearing loss. To create a mouse model of this disease, a mutant line was created with targeted disruption of the gene. Cochlear function is normal in these mutants when maintained on a high-thiamine diet. When challenged with a low-thiamine diet, Slc19a2-null mice showed 40-60 dB threshold elevations by auditory brainstem response (ABR), but only 10-20 dB elevation by otoacoustic emission (OAE) measures. Wild-type mice retain normal hearing on either diet. Cochlear histological analysis showed a pattern uncommon for sensorineural hearing loss: selective loss of inner hair cells after 1-2 weeks on low thiamine and significantly greater inner than outer hair cell loss after longer low-thiamine challenges. Such a pattern is consistent with the observed discrepancy between ABR and OAE threshold shifts. The possible role of thiamine transport in other reported cases of selective inner hair cell loss is considered.

  6. Hair loss and regeneration performed on animal models

    PubMed Central

    ORASAN, MEDA SANDRA; ROMAN, IULIA IOANA; CONEAC, ANDREI; MURESAN, ADRIANA; ORASAN, REMUS IOAN

    2016-01-01

    Research in the field of reversal hair loss remains a challenging subject. As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical treatments for inducing hair regrowth, research is necessary in order to improve therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell type - dermal papilla or organ culture of isolated cell follicles. In vivo research on this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking into consideration the advantages and disadvantages of each animal model and the depilation options. Further studies are required not only to compare the efficiency of different therapies but more importantly to establish their long term safety. PMID:27547051

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

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  8. Finasteride treatment of female pattern hair loss.

    PubMed

    Iorizzo, Matilde; Vincenzi, Colombina; Voudouris, Stylianos; Piraccini, Bianca Maria; Tosti, Antonella

    2006-03-01

    To evaluate the efficacy of oral finasteride therapy associated with an oral contraceptive containing drospirenone and ethinyl estradiol in premenopausal women with female pattern hair loss. Outpatient consultation for hair disorders at the Department of Dermatology, University of Bologna. Thirty-seven women with female pattern hair loss were treated with oral finasteride, 2.5 mg/d, while taking an oral contraceptive containing drospirenone and ethinyl estradiol. Treatment efficacy was evaluated using global photography and the hair density score from videodermoscopy. A self-administered questionnaire was used to assess patient evaluation of treatment effectiveness. At 12-month follow-up, 23 of the 37 patients were rated as improved using global photography (12 were slightly improved, 8 were moderately improved, and 3 were greatly improved). No improvement was recorded in 13 patients. One patient experienced worsening of the condition. There was a statistically significant (P = .002) increase in the hair density score in 12 patients. No adverse reactions to the drug were reported. Sixty-two percent of the patients demonstrated some improvement of their hair loss with the use of finasteride, 2.5 mg/d, while taking the oral contraceptive. It is unclear whether the success was due to a higher dosage of finasteride (2.5 mg instead of 1 mg) or to its association with the oral contraceptive containing drospirenone, which has an antiandrogenic effect. Further studies are necessary to understand which patterns of female pattern hair loss respond better to this treatment.

  9. New Treatments for Hair Loss.

    PubMed

    Vañó-Galván, S; Camacho, F

    2017-04-01

    The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients' quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of topical application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    PubMed Central

    Perez, Philip; Bao, Jianxin

    2011-01-01

    Age-related decline of cochlear function is mainly due to the loss of hair cells and spiral ganglion neurons (SGNs). Recent findings clearly indicate that survival of these two cell types during aging depends on genetic and environmental interactions, and this relationship is seen at the systemic, tissue, cellular, and molecular levels. At cellular and molecular levels, age-related loss of hair cells and SGNs can occur independently, suggesting distinct mechanisms for the death of each during aging. This mechanistic independence is also observed in the loss of medial olivocochlear efferent innervation and outer hair cells during aging, pointing to a universal independent cellular mechanism for age-related neuronal death in the peripheral auditory system. While several molecular signaling pathways are implicated in the age-related loss of hair cells and SGNs, studies with the ability to locally modify gene expression in these cell types are needed to address whether these signaling pathways have direct effects on hair cells and SGNs during aging. Finally, the issue of whether age-related loss of these cells occurs via typical apoptotic pathways requires further examination. As new studies in the field of aging reshape the framework for exploring these underpinnings, understanding of the loss of hair cells and SGNs associated with age and the interventions that can treat and prevent these changes will result in dramatic benefits for an aging population. PMID:22396875

  11. Low-Level Laser (Light) Therapy (LLLT) for Treatment of Hair Loss

    PubMed Central

    Avci, Pinar; Gupta, Gaurav K.; Clark, Jason; Wikonkal, Norbert; Hamblin, Michael R.

    2013-01-01

    Objective Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia, the most common type, affects 50% of males over the age of 40 and 75% of females over 65. Only two drugs have been approved so far (minoxidil and finasteride) and hair transplant is the other treatment alternative. This review surveys the evidence for low-level laser therapy (LLLT) applied to the scalp as a treatment for hair loss and discusses possible mechanisms of actions. Methods and Materials Searches of PubMed and Google Scholar were carried out using keywords alopecia, hair loss, LLLT, photobiomodulation. Results Studies have shown that LLLT stimulated hair growth in mice subjected to chemotherapy-induced alopecia and also in alopecia areata. Controlled clinical trials demonstrated that LLLT stimulated hair growth in both men and women. Among various mechanisms, the main mechanism is hypothesized to be stimulation of epidermal stem cells in the hair follicle bulge and shifting the follicles into anagen phase. Conclusion LLLT for hair growth in both men and women appears to be both safe and effective. The optimum wavelength, coherence and dosimetric parameters remain to be determined. PMID:23970445

  12. Low-level laser (light) therapy (LLLT) for treatment of hair loss.

    PubMed

    Avci, Pinar; Gupta, Gaurav K; Clark, Jason; Wikonkal, Norbert; Hamblin, Michael R

    2014-02-01

    Alopecia is a common disorder affecting more than half of the population worldwide. Androgenetic alopecia, the most common type, affects 50% of males over the age of 40 and 75% of females over 65. Only two drugs have been approved so far (minoxidil and finasteride) and hair transplant is the other treatment alternative. This review surveys the evidence for low-level laser therapy (LLLT) applied to the scalp as a treatment for hair loss and discusses possible mechanisms of actions. Searches of PubMed and Google Scholar were carried out using keywords alopecia, hair loss, LLLT, photobiomodulation. Studies have shown that LLLT stimulated hair growth in mice subjected to chemotherapy-induced alopecia and also in alopecia areata. Controlled clinical trials demonstrated that LLLT stimulated hair growth in both men and women. Among various mechanisms, the main mechanism is hypothesized to be stimulation of epidermal stem cells in the hair follicle bulge and shifting the follicles into anagen phase. LLLT for hair growth in both men and women appears to be both safe and effective. The optimum wavelength, coherence and dosimetric parameters remain to be determined. © 2013 Wiley Periodicals, Inc.

  13. Hair cell regeneration

    PubMed Central

    Edge, Albert SB; Chen, Zheng-Yi

    2017-01-01

    The mammalian inner ear largely lacks the capacity to regenerate hair cells, the sensory cells required for hearing and balance. Recent studies in both lower vertebrates and mammals have uncovered genes and pathways important in hair cell development and have suggested ways that the sensory epithelia could be manipulated to achieve hair cell regeneration. These approaches include the use of inner ear stem cells, transdifferentiation of nonsensory cells, and induction of a proliferative response in the cells that can become hair cells. PMID:18929656

  14. Induction of differentiation of human embryonic stem cells into functional hair-cell-like cells in the absence of stromal cells.

    PubMed

    Ding, Jie; Tang, Zihua; Chen, Jiarong; Shi, Haosong; Chen, Jianling; Wang, Cuicui; Zhang, Cui; Li, Liang; Chen, Ping; Wang, Jinfu

    2016-12-01

    Sensorineural hearing loss and vestibular dysfunction have become the most common forms of sensory defects. Stem cell-based therapeutic strategies for curing hearing loss are being developed. Several attempts to develop hair cells by using chicken utricle stromal cells as feeder cells have resulted in phenotypic conversion of stem cells into inner ear hair-cell-like cells. Here, we induced the differentiation of human embryonic stem cells (hESCs) into otic epithelial progenitors (OEPs), and further induced the differentiation of OEPs into hair-cell-like cells using different substrates. Our results showed that OEPs cultured on the chicken utricle stromal cells with the induction medium could differentiate into hair-cell-like cells with stereociliary bundles. Co-culture with stromal cells, however, may be problematic for subsequent examination of the induced hair-cell-like cells. In order to avoid the interference from stromal cells, we cultured OEPs on laminin with different induction media and examined the effects of the induction medium on the differentiation potentials of OEPs into hair-cell-like cells. The results revealed that the culture of OEPs on laminin with the conditioned medium from chicken utricle stromal cells supplemented with EGF and all-trans retinoic acid (RA) could promote the organization of cells into epithelial clusters displaying hair-cell-like cells with stereociliary bundles. These cells also displayed the expected electrophysiological properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Trichoscopic Findings of Hair Loss in Koreans

    PubMed Central

    Park, Jin; Kim, Joo-Ik; Kim, Han-Uk; Yun, Seok-Kweon

    2015-01-01

    Background Trichoscopic findings of hair loss have been well described for the differential diagnosis of alopecia; however, critical findings were not thoroughly investigated or compared among all ethnic groups, including Asians. Objective We aimed to find any characteristic trichoscopic findings in Korean alopecia patients and to verify whether those findings are closely related to previously reported observations. Methods Three hundred and twenty-seven patients with hair loss of various causes and 160 normal scalps were analyzed. Trichoscopic examination was performed with a polarized-light handheld dermoscope. Results A total of 35 patterns of trichoscopic features were represented, and certain features were significantly common or observed exclusively in a particular type of alopecia as follows: yellow dots, exclamation mark hairs, and proximal tapering hairs (alopecia areata), trichoptilosis and pointed hairs (trichotillomania), corkscrew hairs, septate hyphae hairs, and comma hairs (tinea capitis), diffuse white area, fibrotic white dots, and tufting hairs (primary cicatricial alopecia), hair diameter diversity and peripilar sign (androgenetic alopecia), and short nonvellus hairs (telogen effluvium). Conclusion The characteristic trichoscopic features for the differential diagnosis of alopecia in Koreans, shown as follicular, perifollicular, and hair shaft patterns, are similar to those of Caucasians; however, the frequencies of the pigment patterns are different between Koreans and Caucasians because of the contrast effect of the skin and hair color. Therefore, racial difference should be considered in the trichoscopic evaluation for differential diagnosis. PMID:26512168

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

    PubMed

    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.

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

    PubMed Central

    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

  18. Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells.

    PubMed

    McLean, Will J; Yin, Xiaolei; Lu, Lin; Lenz, Danielle R; McLean, Dalton; Langer, Robert; Karp, Jeffrey M; Edge, Albert S B

    2017-02-21

    Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor. The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    PubMed

    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 < 0.01). The production of reactive oxygen species significantly increased by 183% with 125 μM 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 < 0.01) and a significantly increased DASPEI reactivity (reflecting viable mitochondria, p < 0.01) were observed in 40 μM/ml ES pre-treatment group. Our data suggest that ES could protect against neomycin-induced hair cell loss possibly by reducing

  20. Hair growth promoting effect of white wax and policosanol from white wax on the mouse model of testosterone-induced hair loss.

    PubMed

    Wang, Zhan-di; Feng, Ying; Ma, Li-Yi; Li, Xian; Ding, Wei-Feng; Chen, Xiao-Ming

    2017-05-01

    White wax (WW) has been traditionally used to treat hair loss in China. However there has been no reporter WW and its extract responsible for hair growth-promoting effect on androgenetic alopecia. In this paper, we examined the hair growth-promoting effects of WW and policosanol of white wax (WWP) on model animal of androgenetic alopecia and the potential target cell of WW and WWP. WW (1, 10 and 20%) and WWP (0.5, 1 and 2%) were applied topically to the backs of mice. Finasteride (2%) was applied topically as a positive control. MTS assays were performed to evaluate cell proliferation in culture human follicle dermal papilla cells (HFDPCs). The inhibition of WW and WWP for 5α- reductase were tested in Vitro. Results showed more lost hairs were clearly seen in mice treated with TP only and TP plus vehicle. Mice which received TP plus WW and WWP showed less hair loss. WW and WWP showed an outstanding hair growth-promoting activity as reflected by the follicular length, follicular density, A/T ratio, and hair bulb diameter. The optimal treatment effect was observed at 10% WW and 1% WWP, which were better than 2% finasteride treatment. MTS assay results suggested that WW and WWP remarkably increased the proliferation of HFDPCs. Inhibitor assay of 5α- reductase showed that WW and WWP inhibited significantly the conversion of testosterone to dihydrotesterone, and the IC 50 values of WW and WWP were higher than that of finasteride. In Conclusion, WW and WWP could act against testosterone-induced alopecia in mice, and they promoted hair growth by inhibiting 5α-reductase activity and HFDPCs proliferation. DPCs is the target cell of WW and WWP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Negative hair-bundle stiffness betrays a mechanism for mechanical amplification by the hair cell.

    PubMed

    Martin, P; Mehta, A D; Hudspeth, A J

    2000-10-24

    Hearing and balance rely on the ability of hair cells in the inner ear to sense miniscule mechanical stimuli. In each cell, sound or acceleration deflects the mechanosensitive hair bundle, a tuft of rigid stereocilia protruding from the cell's apical surface. By altering the tension in gating springs linked to mechanically sensitive transduction channels, this deflection changes the channels' open probability and elicits an electrical response. To detect weak stimuli despite energy losses caused by viscous dissipation, a hair cell can use active hair-bundle movement to amplify its mechanical inputs. This amplificatory process also yields spontaneous bundle oscillations. Using a displacement-clamp system to measure the mechanical properties of individual hair bundles from the bullfrog's ear, we found that an oscillatory bundle displays negative slope stiffness at the heart of its region of mechanosensitivity. Offsetting the hair bundle's position activates an adaptation process that shifts the region of negative stiffness along the displacement axis. Modeling indicates that the interplay between negative bundle stiffness and the motor responsible for mechanical adaptation produces bundle oscillation similar to that observed. Just as the negative resistance of electrically excitable cells and of tunnel diodes can be embedded in a biasing circuit to amplify electrical signals, negative stiffness can be harnessed to amplify mechanical stimuli in the ear.

  2. Effect of sinapic acid on hair growth promoting in human hair follicle dermal papilla cells via Akt activation.

    PubMed

    Woo, Hyunju; Lee, Seungjun; Kim, Seungbeom; Park, Deokhoon; Jung, Eunsun

    2017-07-01

    Hair loss known as alopecia is caused by abnormal hair follicle cycling including shortening of the anagen (growth) phase and changing of hair follicle morphology with miniaturization. In accordance with the life extension, the quality of life is considered to be a most important thing. The yearning for healthy and beautiful hair and low self esteem due to hair loss had negative influence on the quality of life with psychosocial maladjustment. The objective of this research was to identify new compound that can be used as a drug to promote hair growth. We investigated whether the function of sinapic acid (SA) is able to promote hair growth in human hair follicle dermal papilla cells (hHFDPC). We showed that treatment of SA in hHFDPC could induce proliferation and the activation of Akt signaling in HFDPC. In addition, SA could stimulate the expressions of the several growth factors, insulin-like growth factor 1, and vascular endothelial growth factor for hair growth. We showed that SA led to an increased level of phospho-GSK-3β and β-catenin accumulation in HFDPC. Finally, the promoting effect of SA in hHFDPC cell growth occurred by the induction of cell cycle progression. These results suggest that SA could be one of the potential candidate compounds for the treatment of alopecia by inducing hair growth through triggering the expressions of growth factors via activation of Akt and subsequent inactivation of GSK-3β /β-catenin pathway.

  3. Retinoic Acid Signaling Mediates Hair Cell Regeneration by Repressing p27kip and sox2 in Supporting Cells.

    PubMed

    Rubbini, Davide; Robert-Moreno, Àlex; Hoijman, Esteban; Alsina, Berta

    2015-11-25

    During development, otic sensory progenitors give rise to hair cells and supporting cells. In mammalian adults, differentiated and quiescent sensory cells are unable to generate new hair cells when these are lost due to various insults, leading to irreversible hearing loss. Retinoic acid (RA) has strong regenerative capacity in several organs, but its role in hair cell regeneration is unknown. Here, we use genetic and pharmacological inhibition to show that the RA pathway is required for hair cell regeneration in zebrafish. When regeneration is induced by laser ablation in the inner ear or by neomycin treatment in the lateral line, we observe rapid activation of several components of the RA pathway, with dynamics that position RA signaling upstream of other signaling pathways. We demonstrate that blockade of the RA pathway impairs cell proliferation of supporting cells in the inner ear and lateral line. Moreover, in neuromast, RA pathway regulates the transcription of p27(kip) and sox2 in supporting cells but not fgf3. Finally, genetic cell-lineage tracing using Kaede photoconversion demonstrates that de novo hair cells derive from FGF-active supporting cells. Our findings reveal that RA has a pivotal role in zebrafish hair cell regeneration by inducing supporting cell proliferation, and shed light on the underlying transcriptional mechanisms involved. This signaling pathway might be a promising approach for hearing recovery. Hair cells are the specialized mechanosensory cells of the inner ear that capture auditory and balance sensory input. Hair cells die after acoustic trauma, ototoxic drugs or aging diseases, leading to progressive hearing loss. Mammals, in contrast to zebrafish, lack the ability to regenerate hair cells. Here, we find that retinoic acid (RA) pathway is required for hair cell regeneration in vivo in the zebrafish inner ear and lateral line. RA pathway is activated very early upon hair cell loss, promotes cell proliferation of progenitor cells

  4. Hair cell ribbon synapses

    PubMed Central

    Brandt, Andreas; Lysakowski, Anna

    2010-01-01

    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 apical compartment. Transmitter release occurs at several active zones along the basolateral membrane. The astonishing capability of the hair cell ribbon synapse for temporally precise and reliable sensory coding has been the subject of intense investigation over the past few years. This research has been facilitated by the excellent experimental accessibility of the hair cell. For the same reason, the hair cell serves as an important model for studying presynaptic Ca2+ signaling and stimulus-secretion coupling. In addition to common principles, hair cell synapses differ in their anatomical and functional properties among species, among the auditory and vestibular organs, and among hair cell positions within the organ. Here, we briefly review synaptic morphology and connectivity and then focus on stimulus-secretion coupling at hair cell synapses. PMID:16944206

  5. Guided genetic screen to identify genes essential in the regeneration of hair cells and other tissues.

    PubMed

    Pei, Wuhong; Xu, Lisha; Huang, Sunny C; Pettie, Kade; Idol, Jennifer; Rissone, Alberto; Jimenez, Erin; Sinclair, Jason W; Slevin, Claire; Varshney, Gaurav K; Jones, MaryPat; Carrington, Blake; Bishop, Kevin; Huang, Haigen; Sood, Raman; Lin, Shuo; Burgess, Shawn M

    2018-01-01

    Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury. To understand the mechanism of hair cell regeneration and its association with regeneration of other tissues, we performed a guided mutagenesis screen using zebrafish lateral line hair cells as a screening platform to identify genes that are essential for hair cell regeneration, and further investigated how genes essential for hair cell regeneration were involved in the regeneration of other tissues. We created genetic mutations either by retroviral insertion or CRISPR/Cas9 approaches, and developed a high-throughput screening pipeline for analyzing hair cell development and regeneration. We screened 254 gene mutations and identified 7 genes specifically affecting hair cell regeneration. These hair cell regeneration genes fell into distinct and somewhat surprising functional categories. By examining the regeneration of caudal fin and liver, we found these hair cell regeneration genes often also affected other types of tissue regeneration. Therefore, our results demonstrate guided screening is an effective approach to discover regeneration candidates, and hair cell regeneration is associated with other tissue regeneration.

  6. Reversal of the hair loss phenotype by modulating the estradiol-ANGPT2 axis in the mouse model of female pattern hair loss.

    PubMed

    Endo, Yujiro; Obayashi, Yuko; Ono, Tomoji; Serizawa, Tetsushi; Murakoshi, Michiaki; Ohyama, Manabu

    2018-07-01

    Despite high demand for a remedy, the treatment options for female pattern hair loss (FPHL) are limited. FPHL is frequent in postmenopausal women. In ovariectomized (OVX) mice, which lack β-estradiol (E2) and manifest hair loss mimicking FPHL, E2 supplementation has been shown to increase hair density. However, the mechanism by which E2 exhibits its biological activity remains elusive. To identify the downstream targets of E2 in the context of FPHL pathophysiology and discover a potential therapeutic agent for the E2-dependent subtype of FPHL. Human dermal papilla cells (hDPCs) were cultured with E2, and a microarray analysis was performed to identify the genes regulated by E2. Using OVX mice, the identified gene product was intradermally administered and then quantitative image analysis of hair density was conducted. In silico analysis to link E2 and the identified gene was performed. Global gene expression and bioinformatics analyses revealed that the genes associated with the angiopoietin-2 (ANGPT2) pathway were upregulated by E2 in hDPCs. ANGPT2 was significantly downregulated in OVX mice than in sham-operated mice (P < 0.01). Importantly, hair density was higher in OVX mice treated with ANGPT2 than in control mice (P < 0.05). In silico analysis showed DNA sequences with high possibility of estrogen receptor binding in the promoter region of ANGPT2. The E2-ANGPT2 axis is present in hair follicles. ANGPT2 provides a strategy for the management of E2-dependent and postmenopausal subsets of FPHL. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  7. Female Pattern Hair Loss: a clinical and pathophysiological review*

    PubMed Central

    Ramos, Paulo Müller; Miot, Hélio Amante

    2015-01-01

    Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss. PMID:26375223

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

    PubMed

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

    2009-01-01

    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 disease, the mouse can be studied using a wide variety of genetic and molecular tools. To design a mouse model for vestibular hair cell regeneration research, an aminoglycoside-induced method of complete hair cell elimination was developed in our lab and applied to the murine utricle. Loss of utricular hair cells was observed using scanning electron microscopy, and corroborated by a loss of fluorescent signal in utricles from transgenic mice with GFP-positive hair cells. Regenerative capability was characterized at several time points up to six months following insult. Using scanning electron microscopy, we observed that as early as two weeks after insult, a few immature hair cells, demonstrating the characteristic immature morphology indicative of regeneration, could be seen in the utricle. As time progressed, larger numbers of immature hair cells could be seen along with some mature cells resembling surface morphology of type II hair cells. By six months post-lesion, numerous regenerated hair cells were present in the utricle, however, neither their number nor their appearance was normal. A BrdU assay suggested that at least some of the regeneration of mouse vestibular hair cells involved mitosis. Our results demonstrate that the vestibular sensory epithelium in mice can spontaneously regenerate, elucidate the time course of this process, and identify involvement of mitosis in some cases. These data establish a road map of the murine vestibular regenerative process, which can be

  9. Platelet rich plasma for the management of hair loss: Better alone or in combination?

    PubMed

    Anitua, Eduardo; Pino, Ander; Jaén, Pedro; Navarro, Mª Rogelia

    2018-06-14

    Platelet-rich plasma (PRP) and autologous protein-based treatments have recently emerged as a potential therapeutic approach for hair loss-related disorders including androgenetic alopecia and alopecia areata. The safety and efficacy of repeated intradermal injections of PRP has proved to promote hair growth in a number of randomized clinical trials. Biologically active proteins and cytokines released upon platelet activation have shown to induce folliculogenesis and activate the anagen growing phase of dormant bulbs. Interestingly, further studies have revealed that combining PRP with other hair loss-related products may enhance the final performance of the treatment. These synergistic approaches include Food and Drug Administration (FDA) approved drugs such as finasteride or minoxidil, bioactive macromolecules and cell-based therapies. Here, recent research involving alone or combined therapy with platelet-rich plasma for the management of hair loss-related disorders are outlined and future prospects are discussed. © 2018 Wiley Periodicals, Inc.

  10. The Female Pattern Hair Loss: Review of Etiopathogenesis and Diagnosis

    PubMed Central

    Vujovic, Anja; Del Marmol, Véronique

    2014-01-01

    Female pattern hair loss (FPHL) is the most common hair loss disorder in women. Initial signs may develop during teenage years leading to a progressive hair loss with a characteristic pattern distribution. The condition is characterized by progressive replacement of terminal hair follicles over the frontal and vertex regions by miniaturized follicles, that leads progressively to a visible reduction in hair density. Women diagnosed with FPHL may undergo significant impairment of quality of life. FPHL diagnosis is mostly clinical. Depending on patient history and clinical evaluation, further diagnostic testing may be useful. The purpose of the paper is to review the current knowledge about epidemiology, pathogenesis, clinical manifestations, and diagnosis of FPHL. PMID:24812631

  11. Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses

    PubMed Central

    Bas, E; Van De Water, TR; Gupta, C; Dinh, J; Vu, L; Martínez-Soriano, F; Láinez, JM; Marco, J

    2012-01-01

    BACKGROUND AND PURPOSE Exposure to an ototoxic level of an aminoglycoside can result in hearing loss. In this we study investigated the otoprotective efficacy of dexamethasone (DXM), melatonin (MLT) and tacrolimus (TCR) in gentamicin (GM)-treated animals and cultures. EXPERIMENTAL APPROACH Wistar rats were divided into controls (treated with saline); exposed to GM only (GM); and three GM-exposed groups treated with either DXM, MLT or TCR. Auditory function and cochlear surface preparations were studied. In vitro studies of oxidative stress, pro-inflammatory cytokine mRNA levels, the MAPK pathway and caspase-3 activation were performed in organ of Corti explants from 3-day-old rats. KEY RESULTS DXM, MLT and TCR decreased levels of reactive oxygen species in GM-exposed explants. The mRNA levels of TNF-α, IL-1β and TNF-receptor type 1 were significantly reduced in GM + DXM and GM + MLT groups. Phospho-p38 MAPK levels decreased in GM + MLT and GM + TCR groups, while JNK phosphorylation was reduced in GM + DXM and GM + MLT groups. Caspase-3 activation decreased in GM + DXM, GM + MLT and GM + TCR groups. These results were consistent with in vivo results. Local treatment of GM-exposed rat cochleae with either DXM, MLT or TCR preserved auditory function and prevented auditory hair cell loss. CONCLUSIONS AND IMPLICATIONS In organ of Corti explants, GM increased oxidative stress and initiated an inflammatory response that led to the activation of MAPKs and apoptosis of hair cells. The three compounds tested demonstrated otoprotective properties that could be beneficial in the treatment of ototoxicity-induced hearing loss. PMID:22320124

  12. Causes and Consequences of Sensory Hair Cell Damage and Recovery in Fishes.

    PubMed

    Smith, Michael E; Monroe, J David

    2016-01-01

    Sensory hair cells are the mechanotransductive receptors that detect gravity, sound, and vibration in all vertebrates. Damage to these sensitive receptors often results in deficits in vestibular function and hearing. There are currently two main reasons for studying the process of hair cell loss in fishes. First, fishes, like other non-mammalian vertebrates, have the ability to regenerate hair cells that have been damaged or lost via exposure to ototoxic chemicals or acoustic overstimulation. Thus, they are used as a biomedical model to understand the process of hair cell death and regeneration and find therapeutics that treat or prevent human hearing loss. Secondly, scientists and governmental natural resource managers are concerned about the potential effects of intense anthropogenic sounds on aquatic organisms, including fishes. Dr. Arthur N. Popper and his students, postdocs and research associates have performed pioneering experiments in both of these lines of fish hearing research. This review will discuss the current knowledge regarding the causes and consequences of both lateral line and inner ear hair cell damage in teleost fishes.

  13. Sonic Hedgehog Initiates Cochlear Hair Cell Regeneration through Downregulation of Retinoblastoma Protein

    PubMed Central

    Lu, Na; Chen, Yan; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei

    2013-01-01

    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. PMID:23211596

  14. Foxi3 deficiency compromises hair follicle stem cell specification and activation

    PubMed Central

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

    2017-01-01

    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. 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 hair germ 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 hair germ activation leading to progressive depletion of stem cells. Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. PMID:26992132

  15. Finasteride treatment of patterned hair loss in normoandrogenic postmenopausal women.

    PubMed

    Trüeb, Ralph M

    2004-01-01

    Finasteride, an inhibitor of type 2 5alpha-reductase, inhibits conversion of testosterone to dihydrotestosterone, resulting in a decrease in serum and scalp dihydrotestosterone levels believed to be pathogenic in androgenetic alopecia. Oral finasteride has been shown to be effective in the treatment of hair loss in men, while its efficacy in women has remained controversial. 5 postmenopausal women without clinical or laboratory signs of hyperandrogenism were given 2.5 or 5 mg/day oral finasteride for the treatment of pattern hair loss. Efficacy was evaluated by patient and investigator assessments, and review of photographs taken at baseline and at months 6, 12 and 18 by an expert panel. Finasteride treatment improved scalp hair by all evaluation techniques. The patients' self-assessment demonstrated that finasteride treatment decreased hair loss, increased hair growth and improved appearance of hair. These improvements were confirmed by investigator assessment and assessments of photographs. No adverse effects were noted. Oral finasteride in a dosage of 2.5 mg/day or more may be effective for the treatment of pattern hair loss in postmenopausal women in the absence of clinical or laboratory signs of hyperandrogenism.

  16. Activation of miR-34a/SIRT1/p53 signaling contributes to cochlear hair cell apoptosis: implications for age-related hearing loss.

    PubMed

    Xiong, Hao; Pang, Jiaqi; Yang, Haidi; Dai, Min; Liu, Yimin; Ou, Yongkang; Huang, Qiuhong; Chen, Suijun; Zhang, Zhigang; Xu, Yaodong; Lai, Lan; Zheng, Yiqing

    2015-04-01

    The molecular mechanisms underlying age-related hearing loss are not fully understood, and currently, there is no treatment for this disorder. MicroRNAs have recently been reported to be increasingly associated with age-related diseases and are emerging as promising therapeutic targets. In this study, miR-34a/Sirtuin 1 (SIRT1)/p53 signaling was examined in cochlear hair cells during aging. MiR-34a, p53 acetylation, and apoptosis increased in the cochlea of C57BL/6 mice with aging, whereas an age-related decrease in SIRT1 was observed. In the inner ear HEI-OC1 cell line, miR-34a overexpression inhibited SIRT1, leading to an increase in p53 acetylation and apoptosis. Moreover, miR-34a knockdown increased SIRT1 expression and diminished p53 acetylation, and apoptosis. Additionally, resveratrol, an activator of SIRT1, significantly rescued miR-34a overexpression-induced HEI-OC1 cell death and significantly reduced hearing threshold shifts and hair cell loss in C57BL/6 mice after a 2-month administration. Our results support a link between age-related cochlear hair cell apoptosis and miR-34a/SIRT1/p53 signaling, which may serve as a potential target for age-related hearing loss treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. 5% Minoxidil: treatment for female pattern hair loss.

    PubMed

    Gupta, Aditya K; Foley, Kelly A

    2014-01-01

    Minoxidil is a Health Canada and US FDA-approved medication for hair loss in men and women. While 5% minoxidil foam has been approved for men since 2006, Health Canada and the FDA only approved 5% minoxidil foam for female pattern hair loss (FPHL) in 2014. Recent Phase III clinical trials demonstrated the efficacy of once daily 5% minoxidil foam for treatment of FPHL, where a significant change from baseline in the target area hair count was observed compared to placebo. Similar changes in hair count for 5% foam and twice daily 2% minoxidil solution established noninferiority of the 5% foam formulation. Five percent minoxidil foam provides an additional option for women with FPHL and will soon be available in Canada.

  18. Hair loss at injection sites of mesotherapy for alopecia.

    PubMed

    El-Komy, Mohamed; Hassan, Akmal; Tawdy, Amira; Solimon, Mohamed; Hady, Mohamed Abdel

    2017-12-01

    The side effects of mesotherapy for treatment of various forms of alopecia are often underreported, while scientific data for its efficacy are severely lacking. To demonstrate the late onset side effects of mesotherapy for alopecia. Three patients with androgenetic alopecia showed hair loss after previously uneventful mesotherapy sessions up to 1 year. Clinical, dermoscopic, and histopathological findings suggested an inflammatory scaring process at sites of mesotherapy injections. Mesotherapy for androgenetic alopecia may paradoxically induce hair loss and scarring. Proper regulation and monitoring of the use of mesotherapy products for treating hair loss in women, needs to be addressed. © 2017 Wiley Periodicals, Inc.

  19. Iron plays a certain role in patterned hair loss.

    PubMed

    Park, Song Youn; Na, Se Young; Kim, Jun Hwan; Cho, Soyun; Lee, Jong Hee

    2013-06-01

    Role of iron in hair loss is not clear yet. The purpose of this study was to evaluate the relationship between iron and hair loss. Retrospective chart review was conducted on patients with female pattern hair loss (FPHL) and male pattern hair loss (MPHL). All patients underwent screening including serum ferritin, iron, and total iron binding capacity (TIBC), CBC, ESR and thyroid function test. For normal healthy controls, age-sex matched subjects who had visited the hospital for a check-up with no serious disease were selected. A total 210 patients with FPHL (n = 113) and MPHL (n = 97) with 210 healthy controls were analyzed. Serum ferritin concentration (FC) was lower in patients with FPHL (49.27 ± 55.8 µg/L), compared with normal healthy women (77.89 ± 48.32 µg/L) (P < 0.001). Premenopausal FPHL patients turned out to show much lower serum ferritin than age/sex-matched controls (P < 0.001). Among MPHL patients, 22.7% of them showed serum FC lower than 70 µg/L, while no one had serum FC lower 70 µg/L in healthy age matched males. These results suggest that iron may play a certain role especially in premenopausal FPHL. The initial screening of iron status could be of help for hair loss patients.

  20. Manipulating cell fate in the cochlea: a feasible therapy for hearing loss

    PubMed Central

    Fujioka, Masato; Okano, Hideyuki; Edge, Albert SB

    2015-01-01

    Mammalian auditory hair cells do not spontaneously regenerate, unlike hair cells in lower vertebrates including fish and birds. In mammals, hearing loss due to the loss of hair cells is thus permanent and intractable. Recent studies in the mouse have demonstrated spontaneous hair cell regeneration during a short postnatal period, but this regenerative capacity is lost in the adult cochlea. Reduced regeneration coincides with a transition that results in a decreased pool of progenitor cells in the cochlear sensory epithelium. Here, we review the signaling cascades involved in hair cell formation and morphogenesis of the organ of Corti in developing mammals, the changing status of progenitor cells in the cochlea, and the regeneration of auditory hair cells in adult mammals. PMID:25593106

  1. Hair cell transduction, tuning and synaptic transmission in the mammalian cochlea

    PubMed Central

    Fettiplace, Robert

    2017-01-01

    Sound pressure fluctuations striking the ear are conveyed to the cochlea, where they vibrate the basilar membrane on which sit hair cells, the mechanoreceptors of the inner ear. Recordings of hair cell electrical responses have shown that they transduce sound via sub-micrometer deflections of their hair bundles, which are arrays of interconnected stereocilia containing the mechanoelectrical transducer (MET) channels. MET channels are activated by tension in extracellular tip links bridging adjacent stereocilia, and they can respond within microseconds to nanometer displacements of the bundle, facilitated by multiple processes of Ca2+-dependent adaptation. Studies of mouse mutants have produced much detail about the molecular organization of the stereocilia, the tip links and their attachment sites, and the MET channels localized to the lower ends of each tip link. The mammalian cochlea contains two categories of hair cells. Inner hair cells relay acoustic information via multiple ribbon synapses that transmit rapidly without rundown. Outer hair cells are important for amplifying sound-evoked vibrations. The amplification mechanism primarily involves contractions of the outer hair cells, which are driven by changes in membrane potential and mediated by prestin, a motor protein in the outer hair cell lateral membrane. Different sound frequencies are separated along the cochlea, with each hair cell being tuned to a narrow frequency range; amplification sharpens the frequency resolution and augments sensitivity 100-fold around the cell’s characteristic frequency. Genetic mutations and environmental factors such as acoustic overstimulation cause hearing loss through irreversible damage to the hair cells or degeneration of inner hair cell synapses. PMID:28915323

  2. The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing.

    PubMed

    Vogl, Christian; Butola, Tanvi; Haag, Natja; Hausrat, Torben J; Leitner, Michael G; Moutschen, Michel; Lefèbvre, Philippe P; Speckmann, Carsten; Garrett, Lillian; Becker, Lore; Fuchs, Helmut; Hrabe de Angelis, Martin; Nietzsche, Sandor; Kessels, Michael M; Oliver, Dominik; Kneussel, Matthias; Kilimann, Manfred W; Strenzke, Nicola

    2017-11-01

    Lipopolysaccharide-responsive beige-like anchor protein (LRBA) belongs to the enigmatic class of BEACH domain-containing proteins, which have been attributed various cellular functions, typically involving intracellular protein and membrane transport processes. Here, we show that LRBA deficiency in mice leads to progressive sensorineural hearing loss. In LRBA knockout mice, inner and outer hair cell stereociliary bundles initially develop normally, but then partially degenerate during the second postnatal week. LRBA deficiency is associated with a reduced abundance of radixin and Nherf2, two adaptor proteins, which are important for the mechanical stability of the basal taper region of stereocilia. Our data suggest that due to the loss of structural integrity of the central parts of the hair bundle, the hair cell receptor potential is reduced, resulting in a loss of cochlear sensitivity and functional loss of the fraction of spiral ganglion neurons with low spontaneous firing rates. Clinical data obtained from two human patients with protein-truncating nonsense or frameshift mutations suggest that LRBA deficiency may likewise cause syndromic sensorineural hearing impairment in humans, albeit less severe than in our mouse model. © 2017 The Authors.

  3. Female pattern hair loss.

    PubMed

    Herskovitz, Ingrid; Tosti, Antonella

    2013-10-01

    Female pattern hair loss (FPHL) also known as female androgenetic alopecia is a common condition afflicting millions of women that can be cosmetically disrupting. Prompt diagnosis and treatment are essential for obtaining optimal outcome. This review addresses the clinical presentation of female pattern hair loss, its differential diagnosis and treatment modalities. A) Diffuse thinning of the crown region with preservation of the frontal hairline (Ludwig's type) B) The "Christmas tree pattern" where the thinning is wider in the frontal scalp giving the alopecic area a triangular shaped figure resembling a christmas tree. C) Thinning associated with bitemporal recession (Hamilton type). Generally, FPHL is not associated with elevated androgens. Less commonly females with FPHL may have other skin or general signs of hyperandrogenism such as hirsutism, acne, irregular menses, infertility, galactorrhea and insulin resistance. The most common endocrinological abnormality associated with FPHL is polycystic ovarian syndrome (PCOS). The most important diseases to consider in the differential diagnosis of FPHL include Chronic Telogen Effluvium (CTE), Permanent Alopecia after Chemotherapy (PAC), Alopecia Areata Incognito (AAI) and Frontal Fibrosing Alopecia (FFA). This review describes criteria for distinguishing these conditions from FPHL. The only approved treatment for FPHL, which is 2% topical Minoxidil, should be applied at the dosage of 1ml twice day for a minimum period of 12 months. This review will discuss off-label alternative modalities of treatment including 5-alfa reductase inhibitors, antiandrogens, estrogens, prostaglandin analogs, lasers, light treatments and hair transplantation.

  4. Protein loss in human hair from combination straightening and coloring treatments.

    PubMed

    França-Stefoni, Simone Aparecida; Dario, Michelli Ferrera; Sá-Dias, Tânia Cristina; Bedin, Valcinir; de Almeida, Adriano José; Baby, André Rolim; Velasco, Maria Valéria R

    2015-09-01

    Hair chemical treatments, such as dyeing and straightening products, are known to cause damage that can be assessed by protein loss. The aim of this study was to evaluate the hair protein loss caused by combined chemical treatments (dye and relaxer) using the validated bicinchoninic acid (BCA) method. Three kinds of straighteners, based on ammonium thioglycolate, guanidine hydroxide and sodium hydroxide, were evaluated and the least harmful combination indicated. Caucasian virgin dark brown hair tresses were treated with developed natural brown color oxidative hair dyeing and/or straightening commercial products based on ammonium thioglycolate, sodium hydroxide, or guanidine hydroxide. Protein loss quantification was assessed by the validated BCA method which has several advantages for quantifying protein loss in chemically treated hair. When both treatments (straightening and dyeing) were combined, a higher negative effect was observed, particularly for dyed hair treated with sodium hydroxide. In this case, a 356% increase in protein loss relative to virgin hair was observed and 208% in relation to only dyed hair. The combination of dying and relaxers based on ammonium thioglycolate or guanidine hydroxide caused a small increase in protein loss, suggesting that these straightening products could be the best alternatives for individuals wishing to combine both treatments. These results indicated that when application of both types of products is desired, ammonium thioglycolate or guanidine hydroxide should be chosen for the straightening process. © 2015 Wiley Periodicals, Inc.

  5. β-Catenin Is Required for Hair-Cell Differentiation in the Cochlea

    PubMed Central

    Hu, Lingxiang; Jacques, Bonnie E.; Mulvaney, Joanna F.; Dabdoub, Alain

    2014-01-01

    The development of hair cells in the auditory system can be separated into steps; first, the establishment of progenitors for the sensory epithelium, and second, the differentiation of hair cells. Although the differentiation of hair cells is known to require the expression of basic helix-loop-helix transcription factor, Atoh1, the control of cell proliferation in the region of the developing cochlea that will ultimately become the sensory epithelium and the cues that initiate Atoh1 expression remain obscure. We assessed the role of Wnt/β-catenin in both steps in gain- and loss-of-function models in mice. The canonical Wnt pathway mediator, β-catenin, controls the expression of Atoh1. Knock-out of β-catenin inhibited hair-cell, as well as pillar-cell, differentiation from sensory progenitors but was not required to maintain a hair-cell fate once specified. Constitutive activation of β-catenin expanded sensory progenitors by inducing additional cell division and resulted in the differentiation of extra hair cells. Our data demonstrate that β-catenin plays a role in cell division and differentiation in the cochlear sensory epithelium. PMID:24806673

  6. Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium.

    PubMed

    Lewis, Rebecca M; Keller, Jesse J; Wan, Liangcai; Stone, Jennifer S

    2018-07-01

    Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics. In mature basilar papillae, BMP4 mRNA is highly expressed in hair cells, but not in hair cell progenitors (supporting cells). Supporting cells transcribe genes encoding receptors for BMP4 (BMPR1A, BMPR1B, and BMPR2) and effectors of BMP4 signaling (ID transcription factors). Following hair cell destruction, BMP4 transcripts are lost from the sensory epithelium. Using organotypic cultures, we demonstrate that treatments with BMP4 during hair cell destruction prevent supporting cells from upregulating expression of the pro-hair cell transcription factor ATOH1, entering the cell cycle, and fully transdifferentiating into hair cells, but they do not induce cell death. By contrast, noggin, a BMP4 inhibitor, increases numbers of regenerated hair cells. These findings demonstrate that BMP4 antagonizes hair cell regeneration in the chicken basilar papilla, at least in part by preventing accumulation of ATOH1 in hair cell precursors. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Iron Plays a Certain Role in Patterned Hair Loss

    PubMed Central

    Park, Song Youn; Na, Se Young; Kim, Jun Hwan; Cho, Soyun

    2013-01-01

    Role of iron in hair loss is not clear yet. The purpose of this study was to evaluate the relationship between iron and hair loss. Retrospective chart review was conducted on patients with female pattern hair loss (FPHL) and male pattern hair loss (MPHL). All patients underwent screening including serum ferritin, iron, and total iron binding capacity (TIBC), CBC, ESR and thyroid function test. For normal healthy controls, age-sex matched subjects who had visited the hospital for a check-up with no serious disease were selected. A total 210 patients with FPHL (n = 113) and MPHL (n = 97) with 210 healthy controls were analyzed. Serum ferritin concentration (FC) was lower in patients with FPHL (49.27 ± 55.8 µg/L), compared with normal healthy women (77.89 ± 48.32 µg/L) (P < 0.001). Premenopausal FPHL patients turned out to show much lower serum ferritin than age/sex-matched controls (P < 0.001). Among MPHL patients, 22.7% of them showed serum FC lower than 70 µg/L, while no one had serum FC lower 70 µg/L in healthy age matched males. These results suggest that iron may play a certain role especially in premenopausal FPHL. The initial screening of iron status could be of help for hair loss patients. PMID:23772161

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

    PubMed Central

    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 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. PMID:23487317

  9. Generation of hair cells in neonatal mice by β-catenin overexpression in Lgr5-positive cochlear progenitors

    PubMed Central

    Shi, Fuxin; Hu, Lingxiang; Edge, Albert S. B.

    2013-01-01

    Mammalian hair cells do not regenerate, and their loss is a major cause of deafness. We recently identified leucine-rich repeat containing, G-protein-coupled receptor 5 (Lgr5)-expressing cochlear supporting cells with the capacity for self-renewal and hair cell differentiation in vitro. We found that these cells, a subset of cochlear supporting cells, were responsive to Wnt signaling. Here we asked whether these Lgr5-positive cells, despite their lack of contribution to hair cell replacement after degenerative loss, could be driven by forced expression of β-catenin to act as hair cell progenitors in vivo. We showed that forced stabilization of β-catenin in supporting cells in neonatal animals resulted in proliferation of supporting cells and generation of hair cells. Although β-catenin expression was increased by genetic means in all supporting cells, entry to the cell cycle and differentiation to hair cells of the normally postmitotic cells was restricted to the Lgr5-positive population. Our finding suggests that Wnt/β-catenin can drive Lgr5-positive cells to act as hair cell progenitors, even after their exit from the cell cycle and apparent establishment of cell fate. PMID:23918377

  10. Discussion: Changes in Vocal Production and Auditory Perception after Hair Cell Regeneration.

    ERIC Educational Resources Information Center

    Ryals, Brenda M.; Dooling, Robert J.

    2000-01-01

    A bird study found that with sufficient time and training after hair cell and hearing loss and hair cell regeneration, the mature avian auditory system can accommodate input from a newly regenerated periphery sufficiently to allow for recognition of previously familiar vocalizations and the learning of new complex acoustic classifications.…

  11. Stria vascularis and cochlear hair cell changes in syphilis: A human temporal bone study.

    PubMed

    Hızlı, Ömer; Kaya, Serdar; Hızlı, Pelin; Paparella, Michael M; Cureoglu, Sebahattin

    2016-12-01

    To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis. We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the two groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis did not significantly differ, in any turn of the cochlea, between the 2 groups (P>0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (P<0.026) and in the mean percentage of inner hair cells in the basal (P=0.001), middle (P=0.004), and apical (P=0.018) turns. In 7 samples in our syphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Corti without any cells in addition to the absence of both outer and inner hair cells. In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Stria Vascularis and Cochlear Hair Cell Changes in Syphilis: A Human Temporal Bone Study

    PubMed Central

    Hızlı, Ömer; Kaya, Serdar; Hızlı, Pelin; Paparella, Michael M.; Cureoglu, Sebahattin

    2016-01-01

    Objective To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis Materials and Methods We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the 2 groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). Results In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis area did not significantly differ, in any turn of the cochlea, between the 2 groups (P > 0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (P < 0.026) and in the mean percentage of inner hair cells in the basal (P = 0.001), middle (P = 0.004), and apical (P = 0.018) turns. In 7 samples in our syphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Corti without any cells in addition to the absence of both outer and inner hair cells. Conclusion In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change. PMID:26860231

  13. Female Pattern Hair Loss

    PubMed Central

    Herskovitz, Ingrid; Tosti, Antonella

    2013-01-01

    Context: Female pattern hair loss (FPHL) also known as female androgenetic alopecia is a common condition afflicting millions of women that can be cosmetically disrupting. Prompt diagnosis and treatment are essential for obtaining optimal outcome. This review addresses the clinical presentation of female pattern hair loss, its differential diagnosis and treatment modalities. Evidence Acquisition: A) Diffuse thinning of the crown region with preservation of the frontal hairline (Ludwig’s type) B) The “Christmas tree pattern” where the thinning is wider in the frontal scalp giving the alopecic area a triangular shaped figure resembling a christmas tree. C) Thinning associated with bitemporal recession (Hamilton type). Generally, FPHL is not associated with elevated androgens. Less commonly females with FPHL may have other skin or general signs of hyperandrogenism such as hirsutism, acne, irregular menses, infertility, galactorrhea and insulin resistance. The most common endocrinological abnormality associated with FPHL is polycystic ovarian syndrome (PCOS). Results: The most important diseases to consider in the differential diagnosis of FPHL include Chronic Telogen Effluvium (CTE), Permanent Alopecia after Chemotherapy (PAC), Alopecia Areata Incognito (AAI) and Frontal Fibrosing Alopecia (FFA). This review describes criteria for distinguishing these conditions from FPHL. Conclusions: The only approved treatment for FPHL, which is 2% topical Minoxidil, should be applied at the dosage of 1ml twice day for a minimum period of 12 months. This review will discuss off-label alternative modalities of treatment including 5-alfa reductase inhibitors, antiandrogens, estrogens, prostaglandin analogs, lasers, light treatments and hair transplantation. PMID:24719635

  14. Hair cell regeneration: Look to the future

    NASA Astrophysics Data System (ADS)

    Rubel, Edwin W.

    2005-04-01

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

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

    PubMed Central

    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 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. PMID:25431550

  16. Low iron stores: a risk factor for excessive hair loss in non-menopausal women.

    PubMed

    Deloche, Claire; Bastien, Philippe; Chadoutaud, Stéphanie; Galan, Pilar; Bertrais, Sandrine; Hercberg, Serge; de Lacharrière, Olivier

    2007-01-01

    Iron deficiency has been suspected to represent one of the possible causes of excessive hair loss in women. The aim of our study was to assess this relationship in a very large population of 5110 women aged between 35 and 60 years. Hair loss was evaluated using a standardized questionnaire sent to all volunteers. The iron status was assessed by a serum ferritin assay carried out in each volunteer. Multivariate analysis allowed us to identify three categories: "absence of hair loss" (43%), "moderate hair loss" (48%) and "excessive hair loss" (9%). Among the women affected by excessive hair loss, a larger proportion of women (59%) had low iron stores (< 40 microg/L) compared to the remainder of the population (48%). Analysis of variance and logistic regression show that a low iron store represents a risk factor for hair loss in non-menopausal women.

  17. Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma

    PubMed Central

    Mizutari, Kunio; Fujioka, Masato; Hosoya, Makoto; Bramhall, Naomi; Okano, Hirotaka James; Okano, Hideyuki; Edge, Albert S.B.

    2013-01-01

    SUMMARY Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor, Atoh1, in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre/lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness. PMID:23312516

  18. Physiological Maturation of Regenerating Hair Cells

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.

    2003-01-01

    The bullfrog saccule, a sensor of gravity and substrate-borne vibration, is a model system for hair cell transduction. Saccular hair cells also increase in number throughout adult life and rapidly recover after hair cell damage, making this organ an ideal system for studying hair cell development, repair, and regeneration. We have used of hair cell and supporting cell immunocytochemical markers to identify damaged hair cells and hair cell precursors in organotypic cultures of the bullfrog saccule. We then used an innovative combination of confocal, electron, and time-lapse microscopy to study the fate of damaged hair cells and the origin of new hair cells after gentamicin ototoxicity in normal and mitotically blocked saccular cultures. These studies have shown that gentamicin ototoxicity produces both lethal and sublethal hair cell damage. They have also shown that hair cell recovery in this organ takes place by both the repair of sublethally damaged hair cells and by the replacement of lost hair cells by mitotic regeneration. In parallel studies, we have used biophysical and molecular biological techniques to study the differentiation and innervation of developing, repairing, and regenerating hair cells. More specifically, we have used RT-PCR to obtain the bullfrog homologues of L-type voltage- gated calcium (L-VGCC) and large-conductance Ca(2+)-activated potassium (BK) channel genes. We have then obtained probes for these genes and, using in situ hybridization, begun to examine their expression in the bullfrog saccule and amphibian papilla. We have also used fluorescent-labeled channel toxins and channel toxin derivatives to determine the time of appearance of L-type voltage-gated calcium (L-VGCC) and Ca(2+)-activated potassium (BK) channels and to study dynamic changes in the number, distribution, and co-localization of these proteins in developing, repairing, and regenerating hair cells. Using time-lapse microscopy, we are also studying the dynamic relationship

  19. Cooperative functions of Hes/Hey genes in auditory hair cell and supporting cell development.

    PubMed

    Tateya, Tomoko; Imayoshi, Itaru; Tateya, Ichiro; Ito, Juichi; Kageyama, Ryoichiro

    2011-04-15

    Notch-mediated lateral inhibition has been reported to regulate auditory hair cell and supporting cell development from common precursors. While the Notch effector genes Hes1, Hes5 and Hey1 are expressed in the developing cochlea, inactivation of either of them causes only mild abnormality, suggesting their functional redundancy. To explore the roles of Hes/Hey genes in cochlear development, we examined compound heterozygous or homozygous mutant mice that lacked Hes1, Hes5 and Hey1 alleles. We found that a reduction in Hes/Hey gene dosage led to graded increase of hair cell formation. However, if at least one allele of Hes1, Hes5 or Hey1 was intact, excessive hair cells were accompanied by overproduction of supporting cells, suggesting that the hair cell increase does not occur at the expense of supporting cells, and that each Hes/Hey gene functions to induce supporting cells. By contrast, when all alleles of Hes1, Hes5 and Hey1 were inactivated, the number of hair cells increased more drastically, whereas that of supporting cells was unchanged compared with control, suggesting that supporting cell formation was balanced by their overproduction and fate conversion into hair cells. The increase of the cell numbers seemed to occur after the prosensory domain formation in the mutants because the proliferation state and the size of the prosensory domain were not affected. Thus, Hes1, Hes5 and Hey1 cooperatively inhibit hair cell formation, and one allele of Hes1, Hes5 or Hey1 is sufficient for supporting cell production probably by lateral inhibition in the sensory epithelium. Strikingly, Hes/Hey mutations lead to disorganized cell alignment and polarity and to hearing loss despite hair cell overproduction. These results suggest that Hes/Hey gene dosage is essential not only for generation of appropriate numbers of hair cells and supporting cells by controlling cell proliferation and lateral inhibition but also for the hearing ability by regulating the cell alignment

  20. Hair Follicle Generation by Injections of Adult Human Follicular Epithelial and Dermal Papilla Cells into Nude Mice

    PubMed Central

    Nilforoushzadeh, Mohammadali; Rahimi Jameh, Elham; Jaffary, Fariba; Abolhasani, Ehsan; Keshtmand, Gelavizh; Zarkob, Hajar; Mohammadi, Parvaneh; Aghdami, Nasser

    2017-01-01

    Objective Dermal papilla and hair epithelial stem cells regulate hair formation and the growth cycle. Damage to or loss of these cells can cause hair loss. Although several studies claim to reconstitute hairs using rodent cells in an animal model, additional research is needed to develop a stable human hair follicle reconstitution protocol. In this study, we have evaluated hair induction by injecting adult cultured human dermal papilla cells and a mixture of hair epithelial and dermal papilla cells in a mouse model. Materials and Methods In this experimental study, discarded human scalp skins were used to obtain dermal papilla and hair epithelial cells. After separation, cells were cultured and assessed for their characteristics. We randomly allocated 15 C57BL/6 nude mice into three groups that received injections in their dorsal skin. The first group received cultured dermal papilla cells, the second group received a mixture of cultured epithelial and dermal papilla cells, and the third group (control) received a placebo [phosphate-buffered saline (PBS-)]. Results Histopathologic examination of the injection sites showed evidence of hair growth in samples that received cells compared with the control group. However, the group that received epithelial and dermal papilla cells had visible evidence of hair growth. PKH tracing confirmed the presence of transplanted cells in the new hair. Conclusion Our data showed that injection of a combination of adult human cultured dermal papilla and epithelial cells could induce hair growth in nude mice. This study emphasized that the combination of human adult cultured dermal papilla and epithelial cells could induce new hair in nude mice. PMID:28670518

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lu, Na; Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114; Chen, Yan

    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 showmore » 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.« less

  2. Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line.

    PubMed

    Thomas, Andrew J; Hailey, Dale W; Stawicki, Tamara M; Wu, Patricia; Coffin, Allison B; Rubel, Edwin W; Raible, David W; Simon, Julian A; Ou, Henry C

    2013-03-06

    Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death. Furthermore, we found that the zebrafish mutants mariner (myo7aa) and sputnik (cad23) that lack functional mechanotransduction were resistant to cisplatin-induced hair cell death. Using a fluorescent analog of cisplatin, we found that chemical or genetic inhibition of mechanotransduction prevented its uptake. These findings demonstrate that cisplatin-induced hair cell death is dependent on functional mechanotransduction in the zebrafish lateral line.

  3. Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line

    PubMed Central

    Thomas, Andrew J.; Hailey, Dale W.; Stawicki, Tamara M.; Wu, Patricia; Coffin, Allison B.; Rubel, Edwin W.; Raible, David W.; Simon, Julian A.; Ou, Henry C.

    2013-01-01

    Cisplatin, one of the most commonly used anti-cancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death. Furthermore, we found that the zebrafish mutants mariner (myo7aa) and sputnik (cad23) that lack functional mechanotransduction were resistant to cisplatin-induced hair cell death. Using a fluorescent analogue of cisplatin, we found that chemical or genetic inhibition of mechanotransduction prevented its uptake. These findings demonstrate that cisplatin-induced hair cell death is dependent on functional mechanotransduction in the zebrafish lateral line. PMID:23467357

  4. Zebrafish Models for the Mechanosensory Hair Cell Dysfunction in Usher Syndrome 3 Reveal That Clarin-1 Is an Essential Hair Bundle Protein.

    PubMed

    Gopal, Suhasini R; Chen, Daniel H-C; Chou, Shih-Wei; Zang, Jingjing; Neuhauss, Stephan C F; Stepanyan, Ruben; McDermott, Brian M; Alagramam, Kumar N

    2015-07-15

    Usher syndrome type III (USH3) is characterized by progressive loss of hearing and vision, and varying degrees of vestibular dysfunction. It is caused by mutations that affect the human clarin-1 protein (hCLRN1), a member of the tetraspanin protein family. The missense mutation CLRN1(N48K), which affects a conserved N-glycosylation site in hCLRN1, is a common causative USH3 mutation among Ashkenazi Jews. The affected individuals hear at birth but lose that function over time. Here, we developed an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype. Immunolabeling demonstrated that Clrn1 localized to the hair cell bundles (hair bundles). The clrn1 mutants generated by zinc finger nucleases displayed aberrant hair bundle morphology with diminished function. Two transgenic zebrafish that express either hCLRN1 or hCLRN1(N48K) in hair cells were produced to examine the subcellular localization patterns of wild-type and mutant human proteins. hCLRN1 localized to the hair bundles similarly to zebrafish Clrn1; in contrast, hCLRN1(N48K) largely mislocalized to the cell body with a small amount reaching the hair bundle. We propose that this small amount of hCLRN1(N48K) in the hair bundle provides clarin-1-mediated function during the early stages of life; however, the presence of hCLRN1(N48K) in the hair bundle diminishes over time because of intracellular degradation of the mutant protein, leading to progressive loss of hair bundle integrity and hair cell function. These findings and genetic tools provide an understanding and path forward to identify therapies to mitigate hearing loss linked to the CLRN1 mutation. Mutations in the clarin-1 gene affect eye and ear function in humans. Individuals with the CLRN1(N48K) mutation are born able to hear but lose that function over time. Here, we develop an animal model system using zebrafish transgenesis and gene targeting to provide an explanation for this phenotype

  5. Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological study.

    PubMed

    Cerundolo, R; Mauldin, E A; Goldschmidt, M H; Beyerlein, S L; Refsal, K R; Oliver, J W

    2005-02-01

    Ten Chesapeake Bay retriever (CBRS) dogs with hair loss were recruited in collaboration with the American Chesapeake Club. All dogs had nonpruritic, noninflammatory, regionalized hair loss affecting the same areas of the body in male and female dogs. Hormonal investigations showed increased adrenal and sex steroid concentration in seven cases. Histopathology revealed follicular hyperkeratosis and plugging, follicular atrophy, and occasional melanin clumping with malformed hair shafts. This study suggests that hair loss in CBRS is a breed syndrome in which young adult dogs have hair loss characterized by unusual histological features and abnormal steroid production. A familial predisposition seems likely and selective breeding might reduce the occurrence of this condition.

  6. Hair cell regeneration in sensory epithelia from the inner ear of a urodele amphibian.

    PubMed

    Taylor, Ruth R; Forge, Andrew

    2005-03-28

    The capacity of urodele amphibians to regenerate a variety of body parts is providing insight into mechanisms of tissue regeneration in vertebrates. In this study the ability of the newt, Notophthalmus viridescens, to regenerate inner ear hair cells in vitro was examined. Intact otic capsules were maintained in organotypic culture. Incubation in 2 mM gentamicin for 48 hours resulted in ablation of all hair cells from the saccular maculae. Thus, any hair cell recovery was not due to repair of damaged hair cells. Immature hair cells were subsequently observed at approximately 12 days posttreatment. Their number increased over the following 7-14 days to reach approximately 30% of the normal number. Following incubation of damaged tissue with bromodeoxyuridine (BrdU), labeled nuclei were confined strictly within regions of hair cell loss, indicating that supporting cells entered S-phase. Double labeling of tissue with two different hair cell markers and three different antibodies to BrdU in various combinations, however, all showed that the nuclei of cells that labeled with hair cell markers did not label for BrdU. This suggested that the new hair cells were not derived from those cells that had undergone mitosis. When mitosis was blocked with aphidicolin, new hair cells were still generated. The results suggest that direct phenotypic conversion of supporting cells into hair cells without an intervening mitotic event is a major mechanism of hair cell regeneration in the newt. A similar mechanism has been proposed for the hair cell recovery phenomenon observed in the vestibular organs of mammals. Copyright 2005 Wiley-Liss, Inc.

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

    ERIC Educational Resources Information Center

    Parker, Mark A.

    2011-01-01

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

  8. Effect of the multifunctional cosmetic ingredient sphinganine on hair loss in males and females with diffuse hair reduction

    PubMed Central

    Gerlach, Nicole; Mentel, Matthias; Köhler, Tim; Tuchscherer, Benjamin; Garbe, Birgit; Ülker, Jasmina; Tronnier, Hagen; Heinrich, Ulrike; Farwick, Mike

    2016-01-01

    Sphingolipids are well known to promote keratinocyte differentiation and to induce ceramide production. In addition, they show anti-inflammatory and antimicrobial activities. Thus, the aim of this study is to investigate the potential effect of sphinganine on prolonging the hair anagen rate and improving the overall hair quality and scalp health. The inhibitory potential of sphinganine toward 5-α-reductase was studied using an in vitro assay. The stimulation of the antimicrobial peptide HBD2 by sphinganine was measured by real-time polymerase chain reaction and immunostaining. Sphinganine bioavailability was studied ex vivo using a pig skin model. A placebo-controlled, double-blind study was designed to evaluate the efficacy of sphinganine on hair loss and hair/scalp quality in vivo. In vitro results showed that sphinganine is a potent inhibitor of 5-α-reductase type I that prevents the conversion of testosterone to dihydrotestosterone, a key factor of androgenetic male baldness. In vivo results demonstrated efficacy in reducing non-illness-related hair loss among males. In terms of expert rating, all hair quality and scalp parameters improved after application of sphinganine. Improved scalp health might be linked to the observed increase of the antimicrobial peptide HBD2. Thus, sphinganine is well suited as a topical alternative for the improvement of scalp health and hair quality and anti-hair loss application. PMID:27660477

  9. Topical Treatment of Hair Loss with Formononetin by Modulating Apoptosis.

    PubMed

    Kim, Mi Hye; Choi, You Yeon; Lee, Ji Eun; Kim, Kyuseok; Yang, Woong Mo

    2016-01-01

    Formononetin is one of the main components of red clover plants and its role on hair regrowth against hair loss has not been established yet. In the present study, we assessed the potential effects of formononetin on alopecia, along with impaired hair cycles by induction of apoptosis-regression.Depilated C57BL/6 mice were used for monitoring the hair cycles. Formononetin (1 and 100 µM) was topically treated to the dorsal skin for 14 days. Topical formononetin treatment induced miniaturized hair follicles to recover to normal sizes. Tapering hair shaft began to grow newly, emerging from the hair follicles by formononetin. In addition, formononetin inhibited the activation of caspase-8 and decreased the procaspase-9 expression. As a result of formononetin treatment, anti-apoptotic Bcl-2 was up-regulated, whereas pro-apoptotic Bax and p53 were down-regulated, resulting in a decrease of caspase-3 activation. Formononetin showed the obvious inhibition of apoptosis under terminal deoxynucleotidyl transferase dUTP nick end labeling staining thereafter.Taken together, our findings demonstrate that formononetin exerted the hair regrowth effect on hair loss, in which the underlying mechanisms were associated with Fas/Fas L-induced caspase activation, thus inhibiting apoptosis. Georg Thieme Verlag KG Stuttgart · New York.

  10. Cryopreservation of Hair-Follicle Associated Pluripotent (HAP) Stem Cells Maintains Differentiation and Hair-Growth Potential.

    PubMed

    Hoffman, Robert M; Kajiura, Satoshi; Cao, Wenluo; Liu, Fang; Amoh, Yasuyuki

    2016-01-01

    Hair follicles contain nestin-expressing pluripotent stem cells which originate above the bulge area of the follicle, below the sebaceous gland. We have termed these cells hair follicle-associated pluripotent (HAP) stem cells. We have established efficient cryopreservation methods of the hair follicle that maintain the pluripotency of HAP stem cells as well as hair growth. We cryopreserved the whole hair follicle by slow-rate cooling in TC-Protector medium or in DMSO-containing medium and storage in liquid nitrogen or at -80 °C. After thawing and culture of the cryopreserved whisker follicles, growing HAP stem cells formed hair spheres. The hair spheres contained cells that differentiated to neurons, glial cells, and other cell types. The hair spheres derived from slow-cooling cryopreserved hair follicles were as pluripotent as hair spheres from fresh hair follicles. We have also previously demonstrated that cryopreserved mouse whisker hair follicles maintain their hair-growth potential. DMSO better cryopreserved mouse whisker follicles compared to glycerol. DMSO-cryopreserved hair follicles also maintained the HAP stem cells, evidenced by P75 ntr expression. Subcutaneous transplantation of DMSO-cryopreserved hair follicles in nude mice resulted in extensive hair fiber growth over 8 weeks, indicating the functional recovery of hair-shaft growth of cryopreserved hair follicles. HAP stem cells can be used for nerve and spinal-cord repair. This biobanking of hair follicles can allow each patient the potential for their own stem cell use for regenerative medicine or hair transplantation.

  11. Clinical Evidence of Increase in Hair Growth and Decrease in Hair Loss without Adverse Reactions Promoted by the Commercial Lotion ECOHAIR®.

    PubMed

    Alonso, María Rosario; Anesini, Claudia

    2017-01-01

    Hair exerts protection, sensory functions, thermoregulation, and sexual attractiveness. Hair loss (alopecia) is caused by several diseases, drug intake, hormone imbalance, stress, and infections (Malassesia furfur). Drugs usually used in alopecia produce irreversible systemic and local side effects. An association of extracts of Coffea arabica and Larrea divaricata (ECOHAIR®) is successfully being commercialized in Argentina for hair growth. The aim of this study was to provide scientific support for the efficacy and innocuousness of ECOHAIR® in patients with noncicatricial alopecia during a 3-month treatment. The efficacy was determined through the assessment of an increase in hair volume, improvement in hair looks, growth of new hair, and a decrease in hair loss by the test of hair count and hair traction. The capacity to decrease the amount of dandruff was also evaluated as well as the adverse local effects caused by the treatment. ECOHAIR® spray improved the overall hair volume and appearance; it increased its thickness, induced hair growth, and decreased hair loss. Besides, no adverse local reactions were observed upon treatment with the product. This study provides scientific support for the clinical use of ECOHAIR® as a treatment to be used in noncicatricial alopecia. © 2017 S. Karger AG, Basel.

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

    NASA Technical Reports Server (NTRS)

    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.

  13. Comparative Transduction Mechanisms of Vestibular Otolith Hair Cells

    NASA Technical Reports Server (NTRS)

    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.

  14. Genetics and other factors in the aetiology of female pattern hair loss.

    PubMed

    Redler, Silke; Messenger, Andrew G; Betz, Regina C

    2017-06-01

    Pattern hair loss is the most common form of hair loss in both women and men. Male pattern hair loss, also termed male androgenetic alopecia (M-AGA), is an androgen-dependent trait that is predominantly genetically determined. Androgen-mediated mechanisms are probably involved in female pattern hair loss (FPHL) in some women but the evidence is less strong than in M-AGA; other non-androgenic pathways, including environmental influences, may contribute to the aetiology. Genome-wide association studies have identified several genetic loci for M-AGA and have provided better insight into the underlying biology. However, the role of heritable factors in Female Pattern Hair Loss (FPHL) is largely unknown. Recently published studies have been restricted to candidate gene approaches and could not clearly identify any susceptibility locus/gene for FPHL but suggest that the aetiology differs substantially from that of M-AGA. Hypotheses about possible pathomechanisms of FPHL as well as the results of the genetic studies performed to date are summarized. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed Central

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

    2012-01-01

    Loss of mechanosensory hair cells in the inner ear accounts for many hearing loss and balance disorders. Several beneficial pharmaceutical drugs cause hair cell death as a side effect. These include aminoglycoside antibiotics, such as neomycin, kanamycin and gentamicin, and several cancer chemotherapy drugs, such as cisplatin. Discovering new compounds that protect mammalian hair cells from toxic insults is experimentally difficult because of the inaccessibility of the inner ear. We used the zebrafish lateral line sensory system as an in vivo screening platform to survey a library of FDA-approved pharmaceuticals for compounds that protect hair cells from neomycin, gentamicin, kanamycin and cisplatin. Ten compounds were identified that provide protection from at least two of the four toxins. The resulting compounds fall into several drug classes, including serotonin and dopamine-modulating drugs, adrenergic receptor ligands, and estrogen receptor modulators. The protective compounds show different effects against the different toxins, supporting the idea that each toxin causes hair cell death by distinct, but partially overlapping, mechanisms. Furthermore, some compounds from the same drug classes had different protective properties, suggesting that they might not prevent hair cell death by their known target mechanisms. Some protective compounds blocked gentamicin uptake into hair cells, suggesting that they may block mechanotransduction or other routes of entry. The protective compounds identified in our screen will provide a starting point for studies in mammals as well as further research discovering the cellular signaling pathways that trigger hair cell death. PMID:22967486

  16. Nourkrin: objective and subjective effects and tolerability in persons with hair loss.

    PubMed

    Thom, E

    2006-01-01

    This randomized, double-blind, placebo-controlled study was designed to investigate the efficacy and tolerability of Nourkrin, a new natural agent for the treatment of hair loss based on marine proteins, and minerals and vitamins. Fifty-five subjects with hair loss of different aetiologies participated in the 6-month blinded phase of the study. Objective assessments showed a significant positive effect of treatment on hair growth. Intake of the active preparation for a further 6 months in an open phase indicated a subjective further improvement in hair growth. Exposure of the patients previously treated with placebo to the active preparation for 12 months gave similar results. Tolerability was good and no side-effects were reported. Nourkrin may provide an alternative to pharmacotherapy for the treatment of hair-loss problems in individuals with androgenetic alopecia.

  17. Neuromast hair cells retain the capacity of regeneration during heavy metal exposure.

    PubMed

    Montalbano, G; Capillo, G; Laurà, R; Abbate, F; Levanti, M; Guerrera, M C; Ciriaco, E; Germanà, A

    2018-07-01

    The neuromast is the morphological unit of the lateral line of fishes and is composed of a cluster of central sensory cells (hair cells) surrounded by support and mantle cells. Heavy metals exposure leads to disruption of hair cells within the neuromast. It is well known that the zebrafish has the ability to regenerate the hair cells after damage caused by toxicants. The process of regeneration depends on proliferation, differentiation and cellular migration of sensory and non-sensory progenitor cells. Therefore, our study was made in order to identify which cellular types are involved in the complex process of regeneration during heavy metals exposure. For this purpose, adult zebrafish were exposed to various heavy metals (Arsenic, cadmium and zinc) for 72h. After acute (24h) exposure, immunohistochemical localization of S100 (a specific marker for hair cells) in the neuromasts highlighted the hair cells loss. The immunoreaction for Sox2 (a specific marker for stem cells), at the same time, was observed in the support and mantle cells, after exposure to arsenic and cadmium, while only in the support cells after exposure to zinc. After chronic (72h) exposure the hair cells were regenerated, showing an immunoreaction for S100 protein. At the same exposure time to the three metals, a Sox2 immunoreaction was expressed in support and mantle cells. Our results showed for the first time the regenerative capacity of hair cells, not only after, but also during exposure to heavy metals, demonstrated by the presence of different stem cells that can diversify in hair cells. Copyright © 2018 Elsevier GmbH. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  19. Prevalence of male and female pattern hair loss in Maryborough.

    PubMed

    Gan, Desmond C C; Sinclair, Rodney D

    2005-12-01

    Maryborough, in central Victoria has an approximate population of 8000 and census data is well matched for Australia overall. Australia has compulsory voting and registration on the electoral roll. To determine the age-related prevalence of balding among men and women in Maryborough we conducted a postal survey of 5000 men and women aged 20 or older, and 427 were invited to attend for examination. Additional data was collected on dandruff, presence of gray hair. Supplementary questionnaires were sent to 340 children aged 5-9, attending a coeducational primary school. 1456 adults (34.1%) responded to the questionnaire. 396 attended for examination. The prevalence of androgenetic alopecia (AGA) increased with advancing age. 98.6% of men had bitemporal recession and severity was significantly associated with vertex and mid-frontal hair loss (p <0.01) but not age (p = 0.06). In all, 64.4% of women had bitemporal hair loss, and similar to men there was a significant association with mid-frontal hair loss (p =0.042) but not age (p =0.467). One hundred and forty children with completed questionnaires were examined. All 72 females and 68 males were assessed as stage 1 on the mid-line part and with no bitemporal recession (frequency stage 1 = 100%, 95% CI (confidence interval) 97.4%-100%). A significant but weak positive association existed between presence of gray hair and history of dandruff (p<0.01). The prevalence of mid-frontal hair loss increases with age and affects 57% of women and 73.5% of men aged 80 and over.

  20. Hair bundles of cochlear outer hair cells are shaped to minimize their fluid-dynamic resistance.

    PubMed

    Ciganović, Nikola; Wolde-Kidan, Amanuel; Reichenbach, Tobias

    2017-06-15

    The mammalian sense of hearing relies on two types of sensory cells: inner hair cells transmit the auditory stimulus to the brain, while outer hair cells mechanically modulate the stimulus through active feedback. Stimulation of a hair cell is mediated by displacements of its mechanosensitive hair bundle which protrudes from the apical surface of the cell into a narrow fluid-filled space between reticular lamina and tectorial membrane. While hair bundles of inner hair cells are of linear shape, those of outer hair cells exhibit a distinctive V-shape. The biophysical rationale behind this morphology, however, remains unknown. Here we use analytical and computational methods to study the fluid flow across rows of differently shaped hair bundles. We find that rows of V-shaped hair bundles have a considerably reduced resistance to crossflow, and that the biologically observed shapes of hair bundles of outer hair cells are near-optimal in this regard. This observation accords with the function of outer hair cells and lends support to the recent hypothesis that inner hair cells are stimulated by a net flow, in addition to the well-established shear flow that arises from shearing between the reticular lamina and the tectorial membrane.

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

    PubMed

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

    2016-01-01

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

  2. Beyond generalized hair cells: Molecular cues for hair cell types

    PubMed Central

    Jahan, Israt; Pan, Ning; Kersigo, Jennifer; Fritzsch, Bernd

    2012-01-01

    Basic helix-loop-helix (bHLH) transcription factors (TFs) are crucial for inner ear neurosensory development. The proneural TF Atoh1 regulates the differentiation of hair cells (HCs) whereas Neurog1 and Neurod1 regulate specification and differentiation of neurons, respectively, but also affect HC development. Expression of Delta and Jagged ligands in nascent HCs and Notch receptors in supporting cells induce supporting cell differentiation through the regulation of neurogenic bHLH TFs (such as Hes1, Hes5) and suppression of limited Atoh1 expression. In sensorineural hearing loss, HCs are lost followed by supporting cells and progressive degeneration of neurons, at least in rodents. Regaining complete hearing may require reconstituting the organ of Corti (OC) from scratch, including the two types of HCs, inner (IHC) and outer (OHC) hair cells with the precise sorting of two types of afferent (type I and II) and efferent (lateral, LOC and medial, MOC olivo-cochlear) innervation. We review effects of bHLH TF dosage and their cross-regulation to differentiate HC types in the OC. We categorize findings of specific gene expressions in HCs: 1. as markers without meaning for the regeneration task, 2. as stabilizers who are needed to maintain or complete differentiation, and 3. as decision making genes, expressed and acting early enough to be useful in this process. Only one TF has been characterized that fits the last aspect: Atoh1. We propose that temporal and intensity variations of Atoh1 are naturally modulated to differentiate specific types of HCs. Importantly, the molecular means to modify the Atoh1 expression are at least partially understood and can be readily implemented in the attempts to regenerate specific types of HCs. PMID:23201032

  3. A Review of Surgical Methods (Excluding Hair Transplantation) and Their Role in Hair Loss Management Today

    PubMed Central

    Sattur, Sandeep S

    2011-01-01

    There is more than one way to manage hair loss surgically. Apart from hair transplantation, there are other techniques which have been used by many to treat baldness. This article attempts to review the surgical methodology and philosophy that have acted as guiding lights in the approach to surgical treatment of baldness over the years and reviews the current role of other techniques in the armamentarium of hair restoration surgeons today. PMID:21976899

  4. Interventions for female pattern hair loss.

    PubMed

    van Zuuren, Esther J; Fedorowicz, Zbys; Schoones, Jan

    2016-05-26

    Female pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). The frontal hair line may or may not be preserved. Hair loss can have a serious psychological impact on women. To determine the efficacy and safety of the available options for the treatment of female pattern hair loss in women. We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (2015, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1872), AMED (from 1985), LILACS (from 1982), PubMed (from 1947), and Web of Science (from 1945). We also searched five trial registries and checked the reference lists of included and excluded studies. We included randomised controlled trials that assessed the efficacy of interventions for FPHL in women. Two review authors independently assessed trial quality, extracted data and carried out analyses. We included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.The included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil. Pooled data from six studies indicated that a greater proportion of participants (157/593) treated with minoxidil (2% and one study with 1%) reported a moderate to marked increase in their hair regrowth when compared with placebo (77/555) (risk ratio (RR) = 1.93, 95% confidence interval (CI) 1.51 to 2.47; moderate quality evidence). These results were confirmed by the investigator-rated assessments in seven studies with 1181

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

    PubMed Central

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

    2014-01-01

    Deafness caused by the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, nonmammalian animals (e.g., birds, amphibians, and fish) regenerate damaged hair cells. To understand better the reasons underpinning such disparities in regeneration among vertebrates, we set out to define at high resolution the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line. We performed RNA-Seq analyses on regenerating support cells purified by FACS. The resulting expression data were subjected to pathway enrichment analyses, and the differentially expressed genes were validated in vivo via whole-mount in situ hybridizations. We discovered that cell cycle regulators are expressed hours before the activation of Wnt/β-catenin signaling following hair cell death. We propose that Wnt/β-catenin signaling is not involved in regulating the onset of proliferation but governs proliferation at later stages of regeneration. In addition, and in marked contrast to mammals, our data clearly indicate that the Notch pathway is significantly down-regulated shortly after injury, thus uncovering a key difference between the zebrafish and mammalian responses to hair cell injury. Taken together, our findings lay the foundation for identifying differences in signaling pathway regulation that could be exploited as potential therapeutic targets to promote either sensory epithelium or hair cell regeneration in mammals. PMID:24706903

  6. Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons.

    PubMed

    Tong, Ling; Strong, Melissa K; Kaur, Tejbeer; Juiz, Jose M; Oesterle, Elizabeth C; Hume, Clifford; Warchol, Mark E; Palmiter, Richard D; Rubel, Edwin W

    2015-05-20

    During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN. Cochlear removal in older animals results in little or no neuron death. However, the extent to which hair-cell-specific afferent activity prevents neuronal death in the neonatal brain is unknown. We further explore this phenomenon using a new mouse model that allows temporal control of cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete loss of organ of Corti hair cells within 1 week of injection regardless of the age of injection. Injection of DT did not influence surrounding supporting cells directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of hair cells in neonates resulted in rapid and profound neuronal loss in the ventral CN, but not when hair cells were eliminated at a more mature age. In addition, normal survival of SGNs was dependent on hair cell integrity early in development and less so in mature animals. This defines a previously undocumented critical period for SGN survival. Copyright © 2015 the authors 0270-6474/15/357878-14$15.00/0.

  7. A Practical Approach to the Diagnosis and Management of Hair Loss in Children and Adolescents

    PubMed Central

    Xu, Liwen; Liu, Kevin X.; Senna, Maryanne M.

    2017-01-01

    Hair loss or alopecia is a common and distressing clinical complaint in the primary care setting and can arise from heterogeneous etiologies. In the pediatric population, hair loss often presents with patterns that are different from that of their adult counterparts. Given the psychosocial complications that may arise from pediatric alopecia, prompt diagnosis and management is particularly important. Common causes of alopecia in children and adolescents include alopecia areata, tinea capitis, androgenetic alopecia, traction alopecia, trichotillomania, hair cycle disturbances, and congenital alopecia conditions. Diagnostic tools for hair loss in children include a detailed history, physical examination with a focused evaluation of the child’s hair and scalp, fungal screens, hair pull and tug test, and if possible, light microscopy and/or trichoscopy. Management of alopecia requires a holistic approach including psychosocial support because treatments are only available for some hair loss conditions, and even the available treatments are not always effective. This review outlines the clinical presentations, presents a diagnostic algorithm, and discusses management of these various hair loss disorders. PMID:28791288

  8. Coexistence of giant blue nevus of the scalp with hair loss and alopecia areata.

    PubMed

    Takeichi, Sachiko; Kubo, Yoshiaki; Murao, Kazutoshi; Inoue, Natsuko; Ansai, Shin-ichi; Arase, Seiji

    2011-04-01

    A 43-year-old Japanese man presented with a 13-year history of a grayish macule measuring 7 cm in diameter with sparse hairs on the vertex. Histopathological examination demonstrated two types of melanocytes, spindle-shaped and ovoid cells, with abundant melanin aggregated around the upper part of the pilosebaceous apparatus. Fibrous, thick collagen bundles were also seen surrounding the upper part of the small hair follicles. There was no infiltration of melanocytes or lymphocytes in the lower dermis or adipose tissue. Based on these findings, a diagnosis of blue nevus, cellular type, was made. Giant cellular blue nevi on the scalp are rare, and 11 cases reported in the published work have shown characteristic features such as hair loss and cranial invasion of nevus cells. It should be noted that melanocytes of giant blue nevi have a high potential to damage other organs such as underlying bone and hair follicles. The patient also showed a typical lesion of alopecia areata on the left temporal which was successfully treated with topical corticosteroid. © 2010 Japanese Dermatological Association.

  9. Hair-Loss Preventing Effect of Grateloupia elliptica

    PubMed Central

    Kang, Jung-Il; Kim, Sang-Cheol; Han, Sang-Chul; Hong, Hye-Jin; Jeon, You-Jin; Kim, Bora; Koh, Young-Sang; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2012-01-01

    This study was conducted to evaluate the effect of Grateloupia elliptica, a seaweed native to Jeju Island, Korea, on the prevention of hair loss. When immortalized rat vibrissa dermal papilla cells were treated with extract of G. elliptica, the proliferation of dermal papilla cells significantly increased. In addition, the G. elliptica extract significantly inhibited the activity of 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), a main cause of androgenetic alopecia. On the other hand, the G. elliptica extract promoted PGE2 production in HaCaT cells in a dose-dependent manner. The G. elliptica extract exhibited particularly high inhibitory effect on LPS-stimulated IL-12, IL-6, and TNF-α production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. The G. elliptica extract also showed inhibitory activity against Pityrosporum ovale, a main cause of dandruff. These results suggest that G. elliptica extract has the potential to treat alopecia via the proliferation of dermal papilla, 5α-reductase inhibition, increase of PGE2 production, decrease of LPS-stimulated pro-inflammatory cytokines and inhibitory activity against Pityrosporum ovale. PMID:24116284

  10. Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (alopecia areata).

    PubMed

    Siebenhaar, Frank; Sharov, Andrey A; Peters, Eva M J; Sharova, Tatyana Y; Syska, Wolfgang; Mardaryev, Andrei N; Freyschmidt-Paul, Pia; Sundberg, John P; Maurer, Marcus; Botchkarev, Vladimir A

    2007-06-01

    Alopecia areata (AA) is an autoimmune disorder of the hair follicle characterized by inflammatory cell infiltrates around actively growing (anagen) hair follicles. Substance P (SP) plays a critical role in the cutaneous neuroimmune network and influences immune cell functions through the neurokinin-1 receptor (NK-1R). To better understand the role of SP as an immunomodulatory neuropeptide in AA, we studied its expression and effects on immune cells in a C3H/HeJ mouse model for AA. During early stages of AA development, the number of SP-immunoreactive nerve fibers in skin is increased, compared to non-affected mice. However, during advanced stages of AA, the number of SP-immunoreactive nerves and SP protein levels in skin are decreased, whereas the expression of the SP-degrading enzyme neutral endopeptidase (NEP) is increased, compared to control skin. In AA, NK-1R is expressed on CD8+ lymphocytes and macrophages accumulating around affected hair follicles. Additional SP supply to the skin of AA-affected mice leads to a significant increase of mast cell degranulation and to accelerated hair follicle regression (catagen), accompanied by an increase of CD8+ cells-expressing granzyme B. These data suggest that SP, NEP, and NK-1R serve as important regulators in the molecular signaling network modulating inflammatory response in autoimmune hair loss.

  11. Differential Expression of Unconventional Myosins in Apoptotic and Regenerating Chick Hair Cells Confirms Two Regeneration Mechanisms

    PubMed Central

    DUNCAN, LUKE J.; MANGIARDI, DOMINIC A.; MATSUI, JONATHAN I.; ANDERSON, JULIA K.; McLAUGHLIN-WILLIAMSON, KATE; COTANCHE, DOUGLAS A.

    2008-01-01

    Hair cells of the inner ear are damaged by intense noise, aging, and aminoglycoside antibiotics. Gentamicin causes oxidative damage to hair cells, inducing apoptosis. In mammals, hair cell loss results in a permanent deficit in hearing and balance. In contrast, avians can regenerate lost hair cells to restore auditory and vestibular function. This study examined the changes of myosin VI and myosin VIIa, two unconventional myosins that are critical for normal hair cell formation and function, during hair cell death and regeneration. During the late stages of apoptosis, damaged hair cells are ejected from the sensory epithelium. There was a 4–5-fold increase in the labeling intensity of both myosins and a redistribution of myosin VI into the stereocilia bundle, concurrent with ejection. Two separate mechanisms were observed during hair cell regeneration. Proliferating supporting cells began DNA synthesis 60 hours after gentamicin treatment and peaked at 72 hours postgentamicin treatment. Some of these mitotically produced cells began to differentiate into hair cells at 108 hours after gentamicin (36 hours after bromodeoxyuridine (BrdU) administration), as demonstrated by the colabeling of myosin VI and BrdU. Myosin VIIa was not expressed in the new hair cells until 120 hours after gentamicin. Moreover, a population of supporting cells expressed myosin VI at 78 hours after gentamicin treatment and myosin VIIa at 90 hours. These cells did not label for BrdU and differentiated far too early to be of mitotic origin, suggesting they arose by direct transdifferentiation of supporting cells into hair cells. PMID:17048225

  12. Cytoplasm localization of aminopeptidase M1 and its functional activity in root hair cells and BY-2 cells.

    PubMed

    Lee, Ok Ran; Cho, Hyung-Taeg

    2012-12-01

    Aminopeptidase M1 (APM1) was the first M1 metallopeptidase family member identified in Arabidopsis, isolated by its affinity for the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). A loss-of-function mutation showed various developmental defects in cell division and auxin transport. APM1 was shown to be localized in endomembrane structures, the cytoplasm, and the plasma membrane. These previous results suggested that APM1 has diverse functional roles in different cell and tissue types. Here we report that APM1 localized to the cytoplasm, and its over-expression in the root hair cell caused longer root hair phenotypes. Treatment of aminopeptidase inhibitors caused internalization of auxin efflux PIN-FORMED proteins in root hair cells and suppressed short root hair phenotype of PIN3 overexpression line (PIN3ox). APM1 also localized to the cytoplasm in tobacco BY-2 cells, its over-expression had little effect on auxin transport in these cells.

  13. The genetics of hair-cell function in zebrafish.

    PubMed

    Nicolson, Teresa

    2017-09-01

    Our ears are remarkable sensory organs, providing the important senses of balance and hearing. The complex structure of the inner ear, or 'labyrinth', along with the assorted neuroepithelia, have evolved to detect head movements and sounds with impressive sensitivity. The rub is that the inner ear is highly vulnerable to genetic lesions and environmental insults. According to National Institute of Health estimates, hearing loss is one of the most commonly inherited or acquired sensorineural diseases. To understand the causes of deafness and balance disorders, it is imperative to understand the underlying biology of the inner ear, especially the inner workings of the sensory receptors. These receptors, which are termed hair cells, are particularly susceptible to genetic mutations - more than two dozen genes are associated with defects in this cell type in humans. Over the past decade, a substantial amount of progress has been made in working out the molecular basis of hair-cell function using vertebrate animal models. Given the transparency of the inner ear and the genetic tools that are available, zebrafish have become an increasingly popular animal model for the study of deafness and vestibular dysfunction. Mutagenesis screens for larval defects in hearing and balance have been fruitful in finding key components, many of which have been implicated in human deafness. This review will focus on the genes that are required for hair-cell function in zebrafish, with a particular emphasis on mechanotransduction. In addition, the generation of new tools available for the characterization of zebrafish hair-cell mutants will be discussed.

  14. Membrane Electromechanics at Hair-Cell Synapses

    NASA Astrophysics Data System (ADS)

    Brownell, W. E.; Farrell, B.; Raphael, R. M.

    2003-02-01

    Both outer hair cell electromotility and neurotransmission at the inner hair cell synapse are rapid mechanical events that are synchronized to the hair-cell receptor potential. We analyze whether the forces and potentials resulting from membrane flexoelectricity could affect synaptic vesicle fusion. The results suggest that the coupling of membrane curvature with membrane potential is of sufficient magnitude to influence neurotransmitter release.

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

    NASA Technical Reports Server (NTRS)

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

    1997-01-01

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

  16. 6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

    PubMed

    Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

    2013-01-01

    Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.

  17. 6-Gingerol Inhibits Hair Shaft Growth in Cultured Human Hair Follicles and Modulates Hair Growth in Mice

    PubMed Central

    Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

    2013-01-01

    Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal. PMID:23437345

  18. The effect of plasma rich in growth factors combined with follicular unit extraction surgery for the treatment of hair loss: A pilot study.

    PubMed

    Navarro, Roge M; Pino, Ander; Martinez-Andres, Asunción; Molina, Consuelo; Martinez, Ana María; Martinez, Nahikari; Orive, Gorka; Anitua, Eduardo

    2017-10-26

    Hair transplant surgery using follicular unit extraction technique (FUE) is a common surgical procedure for the treatment of severe hair loss. Blood-derived autologous growth factors have also proved to promote hair regeneration in patients with different types of alopecia. The aim of this study was to evaluate the safety and clinical efficacy of plasma rich in growth factors (PRGF) technology as an adjuvant therapy for FUE surgery in hair loss affected patients. The biologic potential of PRGF was firstly in vitro evaluated over follicular germinal matrix and dermal papilla cells. Afterward, fifteen patients were subjected to routine FUE procedure while 15 patients underwent FUE+PRGF therapy. PRGF group included intradermal injections of growth factors and follicular transfer unit (FTU) preservation in an autologous fibrin clot. Postsurgical patient satisfaction and clinical improvement were evaluated, and PRGF or saline-preserved hair grafts were histomorphometrically analyzed. Follicular cell proliferation and migration was induced after autologous growth factors treatment. PRGF-preserved FTUs presented higher bioactivity signals and improved integrity of perifollicular structures and extracellular matrix proteins such as collagen and elastic fibers. PRGF not only reduced the postsurgical crust healing and hair fixation period, but also decreased the inflammatory pain and itching sensation. This preliminary data demonstrate that PRGF is able to minimize the postsurgical follicle loss and potentiate the performance of grafted hairs. The fibrin clot not only acts as a protective barrier against environmental factors, but also provides a biologically active scaffold that induces resident cell proliferation and maintains an optimal integrity of the grafted hair. © 2017 Wiley Periodicals, Inc.

  19. Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration.

    PubMed

    Qiu, Weiming; Lei, Mingxing; Zhou, Ling; Bai, Xiufeng; Lai, Xiangdong; Yu, Yu; Yang, Tian; Lian, Xiaohua

    2017-06-01

    Regeneration of hair follicles relies on activation of hair follicle stem cells during telogen to anagen transition process in hair cycle. This process is rigorously controlled by intrinsic and environmental factors. 12-o-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, accelerates reentry of hair follicles into anagen phase. However, it is unclear that how TPA promotes the hair regeneration. In the present study, we topically applied TPA onto the dorsal skin of 2-month-old C57BL/6 female mice to examine the activity of hair follicle stem cells and alteration of signaling pathways during hair regeneration. We found that refractory telogen hair follicles entered anagen prematurely after TPA treatment, with the enhanced proliferation of CD34-positive hair follicle stem cells. Meanwhile, we observed Akt signaling was activated in epidermis, hair infundibulum, bulge and hair bulb, and Wnt signaling was also activated after hair follicle stem cells proliferation. Importantly, after overexpression of DKK1, a specific Wnt signaling inhibitor, the accelerated reentry of hair follicles into anagen induced by TPA was abolished. Our data indicated that TPA-induced hair follicle regeneration is associated with activation of Akt and Wnt/β-catenin signaling.

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

    PubMed Central

    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

    2014-01-01

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

  1. Inner ear supporting cells protect hair cells by secreting HSP70

    PubMed Central

    May, Lindsey A.; Kramarenko, Inga I.; Brandon, Carlene S.; Voelkel-Johnson, Christina; Roy, Soumen; Truong, Kristy; Francis, Shimon P.; Monzack, Elyssa L.; Lee, Fu-Shing; Cunningham, Lisa L.

    2013-01-01

    Mechanosensory hair cells are the receptor cells of hearing and balance. Hair cells are sensitive to death from exposure to therapeutic drugs with ototoxic side effects, including aminoglycoside antibiotics and cisplatin. We recently showed that the induction of heat shock protein 70 (HSP70) inhibits ototoxic drug–induced hair cell death. Here, we examined the mechanisms underlying the protective effect of HSP70. In response to heat shock, HSP70 was induced in glia-like supporting cells but not in hair cells. Adenovirus-mediated infection of supporting cells with Hsp70 inhibited hair cell death. Coculture with heat-shocked utricles protected nonheat-shocked utricles against hair cell death. When heat-shocked utricles from Hsp70–/– mice were used in cocultures, protection was abolished in both the heat-shocked utricles and the nonheat-shocked utricles. HSP70 was detected by ELISA in the media surrounding heat-shocked utricles, and depletion of HSP70 from the media abolished the protective effect of heat shock, suggesting that HSP70 is secreted by supporting cells. Together our data indicate that supporting cells mediate the protective effect of HSP70 against hair cell death, and they suggest a major role for supporting cells in determining the fate of hair cells exposed to stress. PMID:23863716

  2. Cochlear hair cell regeneration after noise-induced hearing loss: does regeneration follow development?

    PubMed Central

    Zheng, Fei; Zuo, Jian

    2017-01-01

    Noise-induced hearing loss (NIHL) affects a large number of military personnel and civilians. Regenerating inner-ear cochlear hair cells (HCs) is a promising strategy to restore hearing after NIHL. In this review, we first summarize recent transcriptome profile analysis of zebrafish lateral lines and chick utricles where spontaneous HC regeneration occurs after HC damage. We then discuss recent studies in other mammalian regenerative systems such as pancreas, heart and central nervous system. Both spontaneous and forced HC regeneration occurs in mammalian cochleae in vivo involving proliferation and direct lineage conversion. However, both processes are inefficient and incomplete, and decline with age. For direct lineage conversion in vivo in cochleae and in other systems, further improvement requires multiple factors, including transcription, epigenetic and trophic factors, with appropriate stoichiometry in appropriate architectural niche. Increasing evidence from other systems indicates that the molecular paths of direct lineage conversion may be different from those of normal developmental lineages. We therefore hypothesize that HC regeneration does not have to follow HC development and that epigenetic memory of supporting cells influences the HC regeneration, which may be a key to successful cochlear HC regeneration. Finally, we discuss recent efforts in viral gene therapy and drug discovery for HC regeneration. We hope that combination therapy targeting multiple factors and epigenetic signaling pathways will provide promising avenues for HC regeneration in humans with NIHL and other types of hearing loss. PMID:28034617

  3. Protective effects of edaravone against cisplatin-induced hair cell damage in zebrafish.

    PubMed

    Hong, Seok Jin; Im, Gi Jung; Chang, Jiwon; Chae, Sung Won; Lee, Seung Hoon; Kwon, Soon Young; Jung, Hak Hyun; Chung, Ah Young; Park, Hae Chul; Choi, June

    2013-06-01

    Edaravone is known to have a potent free radical scavenging effect. The objective of the present study was to evaluate the effects of edaravone on cisplatin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). Five day post-fertilization zebrafish larvae were exposed to 1000 μM cisplatin and 50 μM, 100 μM, 250 μM, 500 μM, 750 μM, and 1000 μM concentrations of edaravone for 4h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of the hair cells in the control group that were not exposed to cisplatin. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy. Edaravone protected cisplatin-induced hair cell loss of neuromasts (edaravone 750 μM: 8.7 ± 1.5 cells, cisplatin 1000 μM only: 3.7 ± 0.9 cells; n=10, p<0.0001) and decreased the Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. Structures of mitochondria and hair cell within neuromasts in ultrastructural analysis were preserved in zebrafish exposed to 1000 μM cisplatin and 750 μM edaravone for 4h. Edaravone attenuated cisplatin-induced hair cell damage in zebrafish. The results of the current study suggest that cisplatin induces apoptosis, and the apoptotic cell death can be prevented by treatment with edaravone in zebrafish. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Male frontal fibrosing alopecia with generalised hair loss.

    PubMed

    Chen, Wenchieh; Kigitsidou, Evanthia; Prucha, Hanna; Ring, Johannes; Andres, Christian

    2014-05-01

    Frontal fibrosing alopecia predominantly affects postmenopausal women and is regarded as a variant of lichen planopilaris. Male cases have rarely been reported. Here we describe a 66-year-old man with a typical receding fronto-temporal hair line in a form of scarring alopecia, which shows features of lichen planopilaris in histology. An extensive loss of body hair involving bilateral axillae, limbs and pubic area was also observed. © 2012 The Authors Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.

  5. Ca2+-Permeable AMPARs Mediate Glutamatergic Transmission and Excitotoxic Damage at the Hair Cell Ribbon Synapse.

    PubMed

    Sebe, Joy Y; Cho, Soyoun; Sheets, Lavinia; Rutherford, Mark A; von Gersdorff, Henrique; Raible, David W

    2017-06-21

    We report functional and structural evidence for GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca 2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca 2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immunohistochemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca 2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca 2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss. SIGNIFICANCE STATEMENT A single incidence of noise overexposure causes damage at the hair cell synapse that later leads to neurodegeneration and exacerbates age-related hearing loss. A first step toward understanding cochlear neurodegeneration is to identify the cause of initial excitotoxic damage to the postsynaptic neuron. Using a combination of immunohistochemical, electrophysiological, and Ca 2+ imaging approaches in evolutionarily divergent species, we demonstrate that Ca 2+ -permeable AMPARs (CP-AMPARs) mediate glutamatergic transmission at the adult auditory hair cell synapse. Overexcitation of the terminal causes Ca 2+ accumulation and swelling that can be prevented by blocking CP

  6. Gene Expression by Mouse Inner Ear Hair Cells during Development

    PubMed Central

    Scheffer, Déborah I.; Shen, Jun

    2015-01-01

    Hair cells of the inner ear are essential for hearing and balance. As a consequence, pathogenic variants in genes specifically expressed in hair cells often cause hereditary deafness. Hair cells are few in number and not easily isolated from the adjacent supporting cells, so the biochemistry and molecular biology of hair cells can be difficult to study. To study gene expression in hair cells, we developed a protocol for hair cell isolation by FACS. With nearly pure hair cells and surrounding cells, from cochlea and utricle and from E16 to P7, we performed a comprehensive cell type-specific RNA-Seq study of gene expression during mouse inner ear development. Expression profiling revealed new hair cell genes with distinct expression patterns: some are specific for vestibular hair cells, others for cochlear hair cells, and some are expressed just before or after maturation of mechanosensitivity. We found that many of the known hereditary deafness genes are much more highly expressed in hair cells than surrounding cells, suggesting that genes preferentially expressed in hair cells are good candidates for unknown deafness genes. PMID:25904789

  7. Nutrition and hair: deficiencies and supplements.

    PubMed

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Auditory hair cell innervational patterns in lizards.

    PubMed

    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.

  9. Inhibition of H3K9me2 Reduces Hair Cell Regeneration after Hair Cell Loss in the Zebrafish Lateral Line by Down-Regulating the Wnt and Fgf Signaling Pathways

    PubMed Central

    Tang, Dongmei; Lin, Qin; He, Yingzi; Chai, Renjie; Li, Huawei

    2016-01-01

    The activation of neuromast (NM) supporting cell (SC) proliferation leads to hair cell (HC) regeneration in the zebrafish lateral line. Epigenetic mechanisms have been reported that regulate HC regeneration in the zebrafish lateral line, but the role of H3K9me2 in HC regeneration after HC loss remains poorly understood. In this study, we focused on the role of H3K9me2 in HC regeneration following neomycin-induced HC loss. To investigate the effects of H3K9me2 in HC regeneration, we took advantage of the G9a/GLP-specific inhibitor BIX01294 that significantly reduces the dimethylation of H3K9. We found that BIX01294 significantly reduced HC regeneration after neomycin-induced HC loss in the zebrafish lateral line. BIX01294 also significantly reduced the proliferation of NM cells and led to fewer SCs in the lateral line. In situ hybridization showed that BIX01294 significantly down-regulated the Wnt and Fgf signaling pathways, which resulted in reduced SC proliferation and HC regeneration in the NMs of the lateral line. Altogether, our results suggest that down-regulation of H3K9me2 significantly decreases HC regeneration after neomycin-induced HC loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus H3K9me2 plays a critical role in HC regeneration. PMID:27303264

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

    PubMed

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

    2016-06-03

    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.

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

    PubMed

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

    2015-04-20

    Alopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens. We have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years). Clinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs. Current clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in

  12. Telogen Effluvium Hair Loss

    MedlinePlus

    ... pillow. This is the result of the normal hair growth cycle. Hairs will grow for a few years, ... the name for the resting stage of the hair growth cycle. A telogen effluvium is when some stress ...

  13. PI3K and Inhibitor of Apoptosis Proteins Modulate Gentamicin- Induced Hair Cell Death in the Zebrafish Lateral Line

    PubMed Central

    Wiedenhoft, Heather; Hayashi, Lauren; Coffin, Allison B.

    2017-01-01

    Inner ear hair cell death leads to sensorineural hearing loss and can be a direct consequence of aminoglycoside antibiotic treatment. Aminoglycosides such as gentamicin are effective therapy for serious Gram-negative bacterial infections such as some forms of meningitis, pneumonia, and sepsis. Aminoglycosides enter hair cells through mechanotransduction channels at the apical end of hair bundles and initiate intrinsic cell death cascades, but the precise cell signaling that leads to hair cell death is incompletely understood. Here, we examine the cell death pathways involved in aminoglycoside damage using the zebrafish (Danio rerio). The zebrafish lateral line contains hair cell-bearing organs called neuromasts that are homologous to hair cells of the mammalian inner ear and represents an excellent model to study ototoxicity. Based on previous research demonstrating a role for p53, Bcl2 signaling, autophagy, and proteasomal degradation in aminoglycoside-damaged hair cells, we used the Cytoscape GeneMANIA Database to identify additional proteins that might play a role in neomycin or gentamicin ototoxicity. Our bioinformatics analysis identified the pro-survival proteins phosphoinositide-dependent kinase-1 (PDK1) and X-linked inhibitor of apoptosis protein (Xiap) as potential mediators of gentamicin-induced hair cell damage. Pharmacological inhibition of PDK1 or its downstream mediator protein kinase C facilitated gentamicin toxicity, as did Xiap mutation, suggesting that both PI3K and endogenous Xiap confer protection. Surprisingly, aminoglycoside-induced hair cell death was highly attenuated in wild type Tupfel long-fin (TL fish; the background strain for the Xiap mutant line) compared to wild type ∗AB zebrafish. Pharmacologic manipulation of p53 suggested that the strain difference might result from decreased p53 in TL hair cells, allowing for increased hair cell survival. Overall, our studies identified additional steps in the cell death cascade triggered by

  14. Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.

    PubMed

    Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Mavlonov, Gafurjon Turdalievich; Yi, Tae-Hoo

    2014-01-01

    This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-β) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-β2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-β2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

  15. Vezatin, an integral membrane protein of adherens junctions, is required for the sound resilience of cochlear hair cells

    PubMed Central

    Bahloul, Amel; Simmler, Marie-Christine; Michel, Vincent; Leibovici, Michel; Perfettini, Isabelle; Roux, Isabelle; Weil, Dominique; Nouaille, Sylvie; Zuo, Jian; Zadro, Cristina; Licastro, Danilo; Gasparini, Paolo; Avan, Paul; Hardelin, Jean-Pierre; Petit, Christine

    2009-01-01

    Loud sound exposure is a significant cause of hearing loss worldwide. We asked whether a lack of vezatin, an ubiquitous adherens junction protein, could result in noise-induced hearing loss. Conditional mutant mice bearing non-functional vezatin alleles only in the sensory cells of the inner ear (hair cells) indeed exhibited irreversible hearing loss after only one minute exposure to a 105 dB broadband sound. In addition, mutant mice spontaneously underwent late onset progressive hearing loss and vestibular dysfunction related to substantial hair cell death. We establish that vezatin is an integral membrane protein with two adjacent transmembrane domains, and cytoplasmic N- and C-terminal regions. Late recruitment of vezatin at junctions between MDCKII cells indicates that the protein does not play a role in the formation of junctions, but rather participates in their stability. Moreover, we show that vezatin directly interacts with radixin in its actin-binding conformation. Accordingly, we provide evidence that vezatin associates with actin filaments at cell–cell junctions. Our results emphasize the overlooked role of the junctions between hair cells and their supporting cells in the auditory epithelium resilience to sound trauma. PMID:20049712

  16. Nutrition of women with hair loss problem during the period of menopause

    PubMed Central

    2016-01-01

    During the period of menopause as an effect of changes in hormone status, one of the most common ailments for women is hair loss. Taking into consideration fact that the ingredients of diet contained in various groups of consumed food products are both precursors in steroid hormones synthesis as well as have direct impact on structure, growth and keeping hair in skin integument, this is the reason why nourishing support for women during this period of life as well as during the hair loss therapy is reasonable. Standard value proteins containing Sulphur amino-acids: cysteine and methionine as precursor to keratin hair protein synthesis are basic element of diet conditioning of hair building. Irreplaceable having impact on keeping hair in skin integument is exogenous L-lysine, mainly present in the inner part of hair root is responsible for hair shape and volume. Fats present in the diet take part in steroid hormones synthesis (from cholesterol) thus have influence on keeping hair in skin integument. Women diet should contain products rich in complex carbohydrates, with low glycemic index and load containing fiber regulating carbohydrate-lipid metabolism of the body. Vitamins also have impact on the state of hair: C vitamin, group B and A vitamins. Minerals which influence hair growth are: Zn, Fe, Cu, Se, Si, Mg and Ca. It is worthwhile to pay closer attention to diet in women who besides hormone changes and undertaken pharmacotherapy are additionally exposed to chronic stress and improperly conducted cosmetic's and hairdresser's treatments. PMID:27095961

  17. Nutrition of women with hair loss problem during the period of menopause.

    PubMed

    Goluch-Koniuszy, Zuzanna Sabina

    2016-03-01

    During the period of menopause as an effect of changes in hormone status, one of the most common ailments for women is hair loss. Taking into consideration fact that the ingredients of diet contained in various groups of consumed food products are both precursors in steroid hormones synthesis as well as have direct impact on structure, growth and keeping hair in skin integument, this is the reason why nourishing support for women during this period of life as well as during the hair loss therapy is reasonable. Standard value proteins containing Sulphur amino-acids: cysteine and methionine as precursor to keratin hair protein synthesis are basic element of diet conditioning of hair building. Irreplaceable having impact on keeping hair in skin integument is exogenous L-lysine, mainly present in the inner part of hair root is responsible for hair shape and volume. Fats present in the diet take part in steroid hormones synthesis (from cholesterol) thus have influence on keeping hair in skin integument. Women diet should contain products rich in complex carbohydrates, with low glycemic index and load containing fiber regulating carbohydrate-lipid metabolism of the body. Vitamins also have impact on the state of hair: C vitamin, group B and A vitamins. Minerals which influence hair growth are: Zn, Fe, Cu, Se, Si, Mg and Ca. It is worthwhile to pay closer attention to diet in women who besides hormone changes and undertaken pharmacotherapy are additionally exposed to chronic stress and improperly conducted cosmetic's and hairdresser's treatments.

  18. Motility of vestibular hair cells in the chick.

    PubMed

    Ogata, Y; Sekitani, T

    1993-01-01

    Recent studies of the outer hair cells in cochlea have demonstrated active motilities. However, very little study has been done on the vestibular hair cells (VHCs). The present study shows the motile response of the VHCs induced by application of Ca2+/ATP promoting contraction. Reversible cell shape changes could be shown in 10 of 16 isolated type I hair cells and 9 of 15 isolated type II hair cells by applying the contraction solution. Furthermore, the sensory hair bundles in the utricular epithelium pivoted around the base and stood perpendicularly to the apical borderline of the epithelium in response to the application of the same solution. It is suggested that the contraction of the isolated VHCs may be transferred to tension which causes the sensory hair bundles to restrict their motion in normal tissue, instead of changing the cell shape.

  19. Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole.

    PubMed

    Tucker, J E; Mauzerall, D; Tucker, E B

    1989-07-01

    The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water.

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed

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

    2000-10-24

    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.

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

    NASA Technical Reports Server (NTRS)

    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

  3. Grey hair: clinical investigation into changes in hair fibres with loss of pigmentation in a photoprotected population.

    PubMed

    Kaplan, P D; Polefka, T; Grove, G; Daly, S; Jumbelic, L; Harper, D; Nori, M; Evans, T; Ramaprasad, R; Bianchini, R

    2011-04-01

    Loss of pigmentation in hair fibres is one of the most obvious phenotypic changes with ageing and has been a topic of increasing interest in the study of follicle biology. The onset of greying brings cosmetic complaints that grey fibres are wild or difficult to manage. Of course, these perceptions may be the consequence of visual obviousness rather than underlying physical or chemical differences. Although several studies have compared pigmented and unpigmented fibres, few have tried to control genetic and ethnic difference as well as extrinsic factors such as photoexposure and chemical treatment. We have recruited subjects with salt-and-pepper hair from a population of Old Order Mennonites who, for cultural reasons, are not only prohibited from chemically treating their hair but also limit their exposure to sunlight. Hair samples were examined for elemental composition, surface energy, Young's modulus, break stress, bending modulus, shear modulus and water sorption/desorption isotherm. The parameters were evaluated statistically for global differences, individual differences and typical individual differences. Consistent with previous published literature, few global differences were found between pigmented and unpigmented hair across the population. We do find that many individual subjects had differences between pigmented and unpigmented fibres. These differences tend to be more pronounced in bulk than in surface properties. The small differences in mechanical properties and moisture uptake and loss lend support to the perception by consumers that grey hair is wilder, drier and less manageable. © 2011 TRI/Princeton. Journal compilation. © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

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

    NASA Technical Reports Server (NTRS)

    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. Regional differences in lectin binding patterns of vestibular hair cells

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

    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-acetylglucosamine (WGA), 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 strain 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 I hair cells while labeling, as in the bullfrog, Type II 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.

  6. Serum ferritin and vitamin d in female hair loss: do they play a role?

    PubMed

    Rasheed, H; Mahgoub, D; Hegazy, R; El-Komy, M; Abdel Hay, R; Hamid, M A; Hamdy, E

    2013-01-01

    Evaluation of serum ferritin and vitamin D levels in females with chronic telogen effluvium (TE) or female pattern hair loss (FPHL), in order to validate their role in these common hair loss diseases. Eighty females (18 to 45 years old) with hair loss, in the form of TE or FPHL, and 40 age-matched females with no hair loss were included in the study. Diagnosis was based upon clinical examination as well as trichogram and dermoscopy. Serum ferritin and vitamin D2 levels were determined for each participant. Serum ferritin levels in the TE (14.7 ± 22.1 μg/l) and FPHL (23.9 ± 38.5 μg/l) candidates were significantly lower than in controls (43.5 ± 20.4 μg/l). Serum vitamin D2 levels in females with TE (28.8 ± 10.5 nmol/l) and FPHL (29.1 ± 8.5 nmol/l) were significantly lower than in controls (118.2 ± 68.1 nmol/l; p < 0.001). These levels decreased with increased disease severity. Serum ferritin cut-off values for TE and FPHL were 27.5 and 29.4 μg/l, respectively, and those for vitamin D were 40.9 and 67.9 nmol/l. Low serum ferritin and vitamin D2 are associated with hair loss in females with TE and FPHL. Screening to establish these levels in cases of hair loss and supplementing with them when they are deficient may be beneficial in the treatment of disease. Copyright © 2013 S. Karger AG, Basel.

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

    PubMed Central

    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 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. PMID:11050201

  8. Hair cell regeneration in the avian auditory epithelium.

    PubMed

    Stone, Jennifer S; Cotanche, Douglas A

    2007-01-01

    Regeneration of sensory hair cells in the mature avian inner ear was first described just over 20 years ago. Since then, it has been shown that many other non-mammalian species either continually produce new hair cells or regenerate them in response to trauma. However, mammals exhibit limited hair cell regeneration, particularly in the auditory epithelium. In birds and other non-mammals, regenerated hair cells arise from adjacent non-sensory (supporting) cells. Hair cell regeneration was initially described as a proliferative response whereby supporting cells re-enter the mitotic cycle, forming daughter cells that differentiate into either hair cells or supporting cells and thereby restore cytoarchitecture and function in the sensory epithelium. However, further analyses of the avian auditory epithelium (and amphibian vestibular epithelium) revealed a second regenerative mechanism, direct transdifferentiation, during which supporting cells change their gene expression and convert into hair cells without dividing. In the chicken auditory epithelium, these two distinct mechanisms show unique spatial and temporal patterns, suggesting they are differentially regulated. Current efforts are aimed at identifying signals that maintain supporting cells in a quiescent state or direct them to undergo direct transdifferentiation or cell division. Here, we review current knowledge about supporting cell properties and discuss candidate signaling molecules for regulating supporting cell behavior, in quiescence and after damage. While significant advances have been made in understanding regeneration in non-mammals over the last 20 years, we have yet to determine why the mammalian auditory epithelium lacks the ability to regenerate hair cells spontaneously and whether it is even capable of significant regeneration under additional circumstances. The continued study of mechanisms controlling regeneration in the avian auditory epithelium may lead to strategies for inducing

  9. Natural Compounds as Occult Ototoxins? Ginkgo biloba Flavonoids Moderately Damage Lateral Line Hair Cells.

    PubMed

    Neveux, Sarah; Smith, Nicole K; Roche, Anna; Blough, Bruce E; Pathmasiri, Wimal; Coffin, Allison B

    2017-04-01

    Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine. Using the zebrafish lateral line, we screened a natural products library to identify potential ototoxins. We found that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant, demonstrated significant ototoxicity, killing up to 30 % of lateral line hair cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar levels of ototoxicity. After flavonoid treatment, surviving hair cells demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the health of the remaining hair cells was compromised. We then asked if these flavonoids enter hair cells through the mechanotransduction channel, which is the site of entry for many known ototoxins. High extracellular calcium or the quinoline derivative E6 berbamine significantly protected hair cells from flavonoid damage, implicating the transduction channel as a site of flavonoid uptake. Since known ototoxins activate cellular stress responses, we asked if reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment with the antioxidant D-methionine significantly protected hair cells from each flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How these products affect mammalian hair cells is still an open question and will be the target of future experiments. However, this research demonstrates the potential for ototoxic damage caused by unregulated

  10. The effect of a 1550 nm fractional erbium-glass laser in female pattern hair loss.

    PubMed

    Lee, G-Y; Lee, S-J; Kim, W-S

    2011-12-01

    Female pattern hair loss (FPHL) is the most common cause of hair loss in women, and its prevalence increases with advancing age. Affected women may experience psychological distress and social withdrawal. A variety of laser and light sources have been tried for treatment of hair loss, and some success has been reported. The purpose of this study was to determine the efficacy and safety of a 1550 nm fractional erbium-glass laser in treatment of female pattern hair loss. Twenty eight ethnic South Korean patients with varying degrees of FPHL were enrolled in the study. Patients received ten treatments with a 1550 nm fractional Er:Glass Laser (Mosaic, Lutronic Co., Ltd, Seoul, South Korea) at 2-weeks intervals using the same parameters (5-10 mm tip, 6 mJ pulse energy, 800 spot/cm(2) density, static mode). Phototrichogram and global photographs were taken at baseline and at the end of laser treatment, and analysed for changes in hair density and hair shaft diameter. Global photographs underwent blinded review by three independent dermatologists using a 7-point scale. Patients also answered questionnaires assessing hair growth throughout the study. All adverse effects were reported during the study. Twenty seven patients completed a 5-month schedule of laser treatment. One patient was excluded during treatment due to occurrence of alopecia areata. At the initial visit, mean hair density was 100 ± 14/cm(2) , and mean hair thickness was 58 ± 12 μm. After 5 months of laser treatment, hair density showed a marked increase to 157 ± 28/cm(2) (P < 0.001), and hair thickness also increased to 75 ± 13 μm (P < 0.001). Global photographs showed improvement in 24 (87.5%) of the 27 patients. Two patients (7.4%) reported mild pruritus after laser treatment; however, these resolved within 2 h. A 1550 nm fractional erbium-glass laser irradiation may be an effective and safe treatment option for women with female pattern hair loss. © 2011 The Authors. Journal of the European

  11. Activating Hair Follicle Stem Cells via R-spondin2 to Stimulate Hair Growth.

    PubMed

    Smith, Andrew A; Li, Jingtao; Liu, Bo; Hunter, Daniel; Pyles, Malcolm; Gillette, Martin; Dhamdhere, Girija R; Abo, Arie; Oro, Anthony; Helms, Jill A

    2016-08-01

    Wnt signaling is required for the development of the hair follicle, and for inciting the growth (anagen) phase of the hair cycle. Most strategies to enhance Wnt signaling for hair growth create a state of constitutive Wnt activation, which leads to neoplastic transformation of the epithelial hair matrix. Using Axin2(LacZ/+) and Axin2(Cre/+)R26R(mTmG/+) reporter mice and RNA analyses, we show that Wnt signaling is elevated during anagen, is reduced at the onset of catagen, and can be reamplified in the skin and surrounding hair follicles via intradermal injection of recombinant R-spondin2 protein. Using Lgr5(LacZ/+) reporter mice, we demonstrate that this amplified Wnt environment leads to activation of leucine-rich repeat-containing G-protein coupled receptor 5-positive stem cells in the hair follicle. The onset of catagen is repressed by R-spondin2 injection, and the anagen phase persists. As a consequence, hair shafts grow longer. We conclude that R-spondin2 treatment activates hair follicle stem cells and therefore may have therapeutic potential to promote hair growth. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. The mechanosensory structure of the hair cell requires clarin-1, a protein encoded by Usher syndrome III causative gene.

    PubMed

    Geng, Ruishuang; Melki, Sami; Chen, Daniel H-C; Tian, Guilian; Furness, David N; Oshima-Takago, Tomoko; Neef, Jakob; Moser, Tobias; Askew, Charles; Horwitz, Geoff; Holt, Jeffrey R; Imanishi, Yoshikazu; Alagramam, Kumar N

    2012-07-11

    Mutation in the clarin-1 gene (Clrn1) results in loss of hearing and vision in humans (Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 gene (Clrn1(-/-)) show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca(2+) currents and membrane capacitance from inner hair cells that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] loading, and transduction currents pointed to diminished cochlear hair bundle function in Clrn1(-/-) mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip links and staircase arrangement of stereocilia were not primarily affected by Clrn1(-/-) mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant p.N48K failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p.N48K in clarin-1 (Clrn1(N48K)) supports our in vitro and Clrn1(-/-) mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Furthermore, the ear phenotype in the Clrn1(N48K) mouse suggests that it is a valuable model for ear disease in CLRN1(N48K), the most prevalent Usher syndrome III mutation in North America.

  13. Sensory Hair Cells: An Introduction to Structure and Physiology.

    PubMed

    McPherson, Duane R

    2018-06-18

    Sensory hair cells are specialized secondary sensory cells that mediate our senses of hearing, balance, linear acceleration, and angular acceleration (head rotation). In addition, hair cells in fish and amphibians mediate sensitivity to water movement through the lateral line system, and closely related electroreceptive cells mediate sensitivity to low-voltage electric fields in the aquatic environment of many fish species and several species of amphibian.Sensory hair cells share many structural and functional features across all vertebrate groups, while at the same time they are specialized for employment in a wide variety of sensory tasks. The complexity of hair cell structure is large, and the diversity of hair cell applications in sensory systems exceeds that seen for most, if not all, sensory cell types. The intent of this review is to summarize the more significant structural features and some of the more interesting and important physiological mechanisms that have been elucidated thus far. Outside vertebrates, hair cells are only known to exist in the coronal organ of tunicates. Electrical resonance, electromotility, and their exquisite mechanical sensitivity all contribute to the attractiveness of hair cells as a research subject.

  14. Predicting the location of missing outer hair cells using the electrical signal recorded at the round window

    PubMed Central

    Chertoff, Mark E.; Earl, Brian R.; Diaz, Francisco J.; Sorensen, Janna L.; Thomas, Megan L. A.; Kamerer, Aryn M.; Peppi, Marcello

    2014-01-01

    The electrical signal recorded at the round window was used to estimate the location of missing outer hair cells. The cochlear response was recorded to a low frequency tone embedded in high-pass filtered noise conditions. Cochlear damage was created by either overexposure to frequency-specific tones or laser light. In animals with continuous damage along the partition, the amplitude of the cochlear response increased as the high-pass cutoff frequency increased, eventually reaching a plateau. The cochlear distance at the onset of the plateau correlated with the anatomical onset of outer hair cell loss. A mathematical model replicated the physiologic data but was limited to cases with continuous hair cell loss in the middle and basal turns. The neural contribution to the cochlear response was determined by recording the response before and after application of Ouabain. Application of Ouabain eliminated or reduced auditory neural activity from approximately two turns of the cochlea. The amplitude of the cochlear response was reduced for moderate signal levels with a limited effect at higher levels, indicating that the cochlear response was dominated by outer hair cell currents at high signal levels and neural potentials at low to moderate signal levels. PMID:25190395

  15. Doppler laser imaging predicts response to topical minoxidil in the treatment of female pattern hair loss.

    PubMed

    McCoy, J; Kovacevic, M; Situm, M; Stanimirovic, A; Bolanca, Z; Goren, A

    2016-01-01

    Topical minoxidil is the only drug approved by the US FDA for the treatment of female pattern hair loss. Unfortunately, following 16 weeks of daily application, less than 40% of patients regrow hair. Several studies have demonstrated that sulfotransferase enzyme activity in plucked hair follicles predicts topical minoxidil response in female pattern hair loss patients. However, due to patients’ discomfort with the procedure, and the time required to perform the enzymatic assay it would be ideal to develop a rapid, non-invasive test for sulfotransferase enzyme activity. Minoxidil is a pro-drug converted to its active form, minoxidil sulfate, by sulfotransferase enzymes in the outer root sheath of hair. Minoxidil sulfate is the active form required for both the promotion of hair regrowth and the vasodilatory effects of minoxidil. We thus hypothesized that laser Doppler velocimetry measurement of scalp blood perfusion subsequent to the application of topical minoxidil would correlate with sulfotransferase enzyme activity in plucked hair follicles. In this study, plucked hair follicles from female pattern hair loss patients were analyzed for sulfotransferase enzyme activity. Additionally, laser Doppler velocimetry was used to measure the change in scalp perfusion at 15, 30, 45, and 60 minutes, after the application of minoxidil. In agreement with our hypothesis, we discovered a correlation (r=1.0) between the change in scalp perfusion within 60 minutes after topical minoxidil application and sulfotransferase enzyme activity in plucked hairs. To our knowledge, this is the first study demonstrating the feasibility of using laser Doppler imaging as a rapid, non-invasive diagnostic test to predict topical minoxidil response in the treatment of female pattern hair loss.

  16. Treatment of female pattern hair loss with oral antiandrogens.

    PubMed

    Sinclair, R; Wewerinke, M; Jolley, D

    2005-03-01

    It has not been conclusively established that female pattern hair loss (FPHL) is either due to androgens or responsive to oral antiandrogen therapy. To evaluate the efficacy of oral antiandrogen therapy in the management of women with FPHL using standardized photographic techniques (Canfield Scientific), and to identify clinical and histological parameters predictive of clinical response. For this single-centre, before-after, open intervention study, 80 women aged between 12 and 79 years, with FPHL and biopsy-confirmed hair follicle miniaturization [terminal/vellus (T/V) hair ratio < or = 4 : 1] were photographed at baseline and again after receiving a minimum of 12 months of oral antiandrogen therapy. Forty women received spironolactone 200 mg daily and 40 women received cyproterone acetate, either 50 mg daily or 100 mg for 10 days per month if premenopausal. Women using topical minoxidil were excluded. Standardized photographs of the midfrontal and vertex scalp were taken with the head positioned in a stereotactic device. Images were evaluated by a panel of three clinicians experienced in the assessment of FPHL, blinded to patient details and treatment and using a three-point scale. As there was no significant difference in the results or the trend between spironolactone and cyproterone acetate the results were combined. Thirty-five (44%) women had hair regrowth, 35 (44%) had no clear change in hair density before and after treatment, and 10 (12%) experienced continuing hair loss during the treatment period. Ordinal logistic regression analysis to identify predictors of response revealed no influence of patient age, menopause status, serum ferritin, serum hormone levels, clinical stage (Ludwig) or histological parameters such as T/V ratio or fibrosis. The only significant predictor was midscalp clinical grade, with higher-scale values associated with a greater response (P = 0.013). Eighty-eight percent of women receiving oral antiandrogens could expect to see no

  17. l-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro.

    PubMed

    Tillinger, Joshua A; Gupta, Chhavi; Ila, Kadri; Ahmed, Jamal; Mittal, Jeenu; Van De Water, Thomas R; Eshraghi, Adrien A

    2018-08-01

    The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined. Rat OC explants were exposed to either: (1) saline control (N = 12); (2) TNFα (2 μg/ml, N = 12); (3) TNFα+l-NAC (5 mM, N = 12); (4) TNFα+l-NAC (10 mM, N = 12); or (5) l-NAC (10 mM, N = 12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed. l-NAC (5 and 10 mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5 mM) showed a highly significant reduction of both ROS (p < 0.01) and 4-hydroxy-2-nonenal immunostaining (p < 0.001) compared to TNFα-challenged explants. Total glutathione levels were low in TNFα-challenged explants compared to control and TNFα+l-NAC (5 mM) treated explants (p < 0.001). l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.

  18. Fractional photothermolysis laser treatment of male pattern hair loss.

    PubMed

    Kim, Won-Serk; Lee, Hye In; Lee, Jin Woong; Lim, Yun Young; Lee, Seung Jae; Kim, Beom Joon; Kim, Myeung Nam; Song, Kye Yong; Park, Won Serk

    2011-01-01

    Various trials have been conducted on the management of male pattern hair loss (MPHL). A variety of laser and light sources have been used for the treatment of MPHL. To understand the effects of a 1,550-nm fractional erbium-glass laser on the hair cycle in an alopecia mouse model and to study the clinical effects of the same laser used as treatment for MPHL. Irradiation was applied to the shaved skin of C3H/HeN mice using various energy and density settings and varied irradiation intervals. In a clinical pilot study involving human subjects, 20 participants were treated over five sessions at 2-week intervals. A fractional photothermolysis laser was used at the energy of 5 mJ and a total density of 300 spots/cm(2). In the animal study, the hair stimulation effects were dependent upon the energy level, density, and irradiation interval. The anagen conversion of hair and the increase in Wnt 5a, β-catenin signals were observed. In the human pilot study, incremental improvements in hair density and growth rate were observed. This pilot study showed that a 1,550-nm fractional erbium-glass laser might induce hair growth, but more intensive studies are required to clarify the clinical applications of this treatment. © 2010 by the American Society for Dermatologic Surgery, Inc.

  19. Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans

    PubMed Central

    2013-01-01

    Background Hair is one of the main distinguishing characteristics of mammals and it has many important biological functions. Cetaceans originated from terrestrial mammals and they have evolved a series of adaptations to aquatic environments, which are of evolutionary significance. However, the molecular mechanisms underlying their aquatic adaptations have not been well explored. This study provided insights into the evolution of hair loss during the transition from land to water by investigating and comparing two essential regulators of hair follicle development and hair follicle cycling, i.e., the Hairless (Hr) and FGF5 genes, in representative cetaceans and their terrestrial relatives. Results The full open reading frame sequences of the Hr and FGF5 genes were characterized in seven cetaceans. The sequence characteristics and evolutionary analyses suggested the functional loss of the Hr gene in cetaceans, which supports the loss of hair during their full adaptation to aquatic habitats. By contrast, positive selection for the FGF5 gene was found in cetaceans where a series of positively selected amino acid residues were identified. Conclusions This is the first study to investigate the molecular basis of the hair loss in cetaceans. Our investigation of Hr and FGF5, two indispensable regulators of the hair cycle, provide some new insights into the molecular basis of hair loss in cetaceans. The results suggest that positive selection for the FGF5 gene might have promoted the termination of hair growth and early entry into the catagen stage of hair follicle cycling. Consequently, the hair follicle cycle was disrupted and the hair was lost completely due to the loss of the Hr gene function in cetaceans. This suggests that cetaceans have evolved an effective and complex mechanism for hair loss. PMID:23394579

  20. The Actions of Calcium on Hair Bundle Mechanics in Mammalian Cochlear Hair Cells

    PubMed Central

    Beurg, Maryline; Nam, Jong-Hoon; Crawford, Andrew; Fettiplace, Robert

    2008-01-01

    Sound stimuli excite cochlear hair cells by vibration of each hair bundle, which opens mechanotransducer (MT) channels. We have measured hair-bundle mechanics in isolated rat cochleas by stimulation with flexible glass fibers and simultaneous recording of the MT current. Both inner and outer hair-cell bundles exhibited force-displacement relationships with a nonlinearity that reflects a time-dependent reduction in stiffness. The nonlinearity was abolished, and hair-bundle stiffness increased, by maneuvers that diminished calcium influx through the MT channels: lowering extracellular calcium, blocking the MT current with dihydrostreptomycin, or depolarizing to positive potentials. To simulate the effects of Ca2+, we constructed a finite-element model of the outer hair cell bundle that incorporates the gating-spring hypothesis for MT channel activation. Four calcium ions were assumed to bind to the MT channel, making it harder to open, and, in addition, Ca2+ was posited to cause either a channel release or a decrease in the gating-spring stiffness. Both mechanisms produced Ca2+ effects on adaptation and bundle mechanics comparable to those measured experimentally. We suggest that fast adaptation and force generation by the hair bundle may stem from the action of Ca2+ on the channel complex and do not necessarily require the direct involvement of a myosin motor. The significance of these results for cochlear transduction and amplification are discussed. PMID:18178649

  1. Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury.

    PubMed

    Nakrieko, Kerry-Ann; Rudkouskaya, Alena; Irvine, Timothy S; D'Souza, Sudhir J A; Dagnino, Lina

    2011-07-15

    Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15--expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury.

  2. Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury

    PubMed Central

    Nakrieko, Kerry-Ann; Rudkouskaya, Alena; Irvine, Timothy S.; D'souza, Sudhir J. A.; Dagnino, Lina

    2011-01-01

    Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15–expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury. PMID:21593206

  3. SENSORY HAIR CELL REGENERATION IN THE ZEBRAFISH LATERAL LINE

    PubMed Central

    Lush, Mark E.; Piotrowski, Tatjana

    2014-01-01

    Damage or destruction of sensory hair cells in the inner ear leads to hearing or balance deficits that can be debilitating, especially in older adults. Unfortunately, the damage is permanent, as regeneration of the inner ear sensory epithelia does not occur in mammals. Zebrafish and other non-mammalian vertebrates have the remarkable ability to regenerate sensory hair cells and understanding the molecular and cellular basis for this regenerative ability will hopefully aid us in designing therapies to induce regeneration in mammals. Zebrafish not only possess hair cells in the ear but also in the sensory lateral line system. Hair cells in both organs are functionally analogous to hair cells in the inner ear of mammals. The lateral line is a mechanosensory system found in most aquatic vertebrates that detects water motion and aids in predator avoidance, prey capture, schooling and mating. Although hair cell regeneration occurs in both the ear and lateral line, most research to date has focused on the lateral line due to its relatively simple structure and accessibility. Here we review the recent discoveries made during the characterization of hair cell regeneration in zebrafish. PMID:25045019

  4. Sensory hair cell regeneration in the zebrafish lateral line.

    PubMed

    Lush, Mark E; Piotrowski, Tatjana

    2014-10-01

    Damage or destruction of sensory hair cells in the inner ear leads to hearing or balance deficits that can be debilitating, especially in older adults. Unfortunately, the damage is permanent, as regeneration of the inner ear sensory epithelia does not occur in mammals. Zebrafish and other non-mammalian vertebrates have the remarkable ability to regenerate sensory hair cells and understanding the molecular and cellular basis for this regenerative ability will hopefully aid us in designing therapies to induce regeneration in mammals. Zebrafish not only possess hair cells in the ear but also in the sensory lateral line system. Hair cells in both organs are functionally analogous to hair cells in the inner ear of mammals. The lateral line is a mechanosensory system found in most aquatic vertebrates that detects water motion and aids in predator avoidance, prey capture, schooling, and mating. Although hair cell regeneration occurs in both the ear and lateral line, most research to date has focused on the lateral line due to its relatively simple structure and accessibility. Here we review the recent discoveries made during the characterization of hair cell regeneration in zebrafish. Copyright © 2014 Wiley Periodicals, Inc.

  5. Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells.

    PubMed

    White, Patricia M; Doetzlhofer, Angelika; Lee, Yun Shain; Groves, Andrew K; Segil, Neil

    2006-06-22

    Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.

  6. Trichotillomania: Bizzare Patern of Hair Loss at 11-Year-old Girl.

    PubMed

    Zímová, Jana; Zímová, Pavlína

    2016-06-01

    Trichotillomania (TTM) is defined by the Diagnostics and Statistic Manual of Mental Disorders, 4th edition (DMS-IV) as hair loss from a patient`s repetitive self-pulling of hair. The disorder is included under anxiety disorders because it shares some obsessive-compulsive features. Patients have the tendency towards feelings of unattractiveness, body dissatisfaction, and low self-esteem (1,2). It is a major psychiatric problem, but many patients with this disorder first present to a dermatologist. An 11-year-old girl came to our department with a 2-month history of diffuse hair loss on the frontoparietal and parietotemporal area (Figure 1). She had originally been examined by a pediatrician with the diagnosis of alopecia areata. The patient`s personal history included hay fever and shortsightedness, and she suffered from varicella and mononucleosis. Nobody in the family history suffered from alopecia areata, but her father has male androgenetic alopecia (Norwood/Hamilton MAGA C3F3). The mother noticed that the child had had changeable mood for about 2 months and did not want to communicate with other persons in the family. The family did not have any pet at home. At school, her favorite subjects were Math and Computer Studies. She did not like Physical Education and did not participate in any sport activities during her free time. This was very strange because she was obese (body-mass index (BMI) 24.69). She was sometimes angry with her 13-year-old sister who had better results at school. The girl had suddenly started to wear a blue scarf. The parents did not notice that she pulled out her hair at home. Dermatological examination of the capillitium found a zone of incomplete alopecia in the frontoparietal and parietotemporal area, without inflammation, desquamation, and scaring. Hairs were of variable length (Figure 1). There was a patch of incomplete alopecia above the forehead between two stripes of hair of variable length (Figure 2). The hair pull test was

  7. Symplastic Transport of Carboxyfluorescein in Staminal Hairs of Setcreasea purpurea Is Diffusive and Includes Loss to the Vacuole 1

    PubMed Central

    Tucker, Joseph E.; Mauzerall, David; Tucker, Edward B.

    1989-01-01

    The kinetics of symplastic transport in staminal hairs of Setcreasea purpurea was studied. The tip cell of a staminal hair was microinjected with carboxyfluorescein (CF) and the symplastic transport of this CF was videotaped and the digital data analyzed to produce kinetic curves. Using a finite difference equation for diffusion between cells and for loss of dye into the vacuole, kinetic curves were calculated and fitted to the observed data. These curves were matched with data from actual microinjection experiments by adjusting K (the coefficient of intercellular junction diffusion) and L (the coefficient of intracellular loss) until a minimum in the least squares difference between the curves was obtained. (a) Symplastic transport of CF was governed by diffusion through intercellular pores (plasmodesmata) and intracellular loss. Diffusion within the cell cytoplasm was never limiting. (b) Each cell and its plasmodesmata must be considered as its own diffusion system. Therefore, a diffusion coefficient cannot be calculated for an entire chain of cells. (c) The movement through plasmodesmata in either direction was the same since the data are fit by a diffusion equation. (d) Diffusion through the intercellular pores was estimated to be slower than diffusion through similar pores filled with water. PMID:16666864

  8. Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin.

    PubMed

    Nakamagoe, Mariko; Tabuchi, Keiji; Nishimura, Bungo; Hara, Akira

    2011-12-11

    As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17β-estradiol (βE2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of βE2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17α-estradiol (αE2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 μM GM for 48h. The effects of βE2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. βE2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182,780. αE2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect; however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of βE2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Continuous hair cell turnover in the inner ear vestibular organs of a mammal, the Daubenton's bat (Myotis daubentonii).

    PubMed

    Kirkegaard, M; Jørgensen, J M

    2000-02-01

    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 20 years, with average lifespans of 4-6 years (Schober and Grimmberger 1989). Further, the young are fully developed and able to fly at the age of 2 months, 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 6 months 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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Technical Reports Server (NTRS)

    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 < 0.001) and eliminated all but remnants of vestibular activity. Virtually complete physiological recovery occurred in all animals studied over a period of 70 days following treatment. Thresholds recovered within two weeks of drug treatment whereas the return of response morphologies including activation latencies and amplitudes required an additional 6-8 weeks.

  12. Stimulation of hair cells with ultraviolet light

    NASA Astrophysics Data System (ADS)

    Azimzadeh, Julien B.; Fabella, Brian A.; Hudspeth, A. J.

    2018-05-01

    Hair bundles are specialized organelles that transduce mechanical inputs into electrical outputs. To activate hair cells, physiologists have resorted to mechanical methods of hair-bundle stimulation. Here we describe a new method of hair-bundle stimulation, irradiation with ultraviolet light. A hair bundle illuminated by ultraviolet light rapidly moves towards its tall edge, a motion typically associated with excitatory stimulation. The motion disappears upon tip-link rupture and is associated with the opening of mechanotransduction channels. Hair bundles can be induced to move sinusoidally with oscillatory modulation of the stimulation power. We discuss the implications of ultraviolet stimulation as a novel hair-bundle stimulus.

  13. Hydrogen protects auditory hair cells from cisplatin-induced free radicals.

    PubMed

    Kikkawa, Yayoi S; Nakagawa, Takayuki; Taniguchi, Mirei; Ito, Juichi

    2014-09-05

    Cisplatin is a widely used chemotherapeutic agent for the treatment of various malignancies. However, its maximum dose is often limited by severe ototoxicity. Cisplatin ototoxicity may require the production of reactive oxygen species (ROS) in the inner ear by activating enzymes specific to the cochlea. Molecular hydrogen was recently established as an antioxidant that selectively reduces ROS, and has been reported to protect the central nervous system, liver, kidney and cochlea from oxidative stress. The purpose of this study was to evaluate the potential of molecular hydrogen to protect cochleae against cisplatin. We cultured mouse cochlear explants in medium containing various concentrations of cisplatin and examined the effects of hydrogen gas dissolved directly into the media. Following 48-h incubation, the presence of intact auditory hair cells was assayed by phalloidin staining. Cisplatin caused hair cell loss in a dose-dependent manner, whereas the addition of hydrogen gas significantly increased the numbers of remaining auditory hair cells. Additionally, hydroxyphenyl fluorescein (HPF) staining of the spiral ganglion showed that formation of hydroxyl radicals was successfully reduced in hydrogen-treated cochleae. These data suggest that molecular hydrogen can protect auditory tissues against cisplatin toxicity, thus providing an additional strategy to protect against drug-induced inner ear damage. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Development and regeneration of vestibular hair cells in mammals.

    PubMed

    Burns, Joseph C; Stone, Jennifer S

    2017-05-01

    Vestibular sensation is essential for gaze stabilization, balance, and perception of gravity. The vestibular receptors in mammals, Type I and Type II hair cells, are located in five small organs in the inner ear. Damage to hair cells and their innervating neurons can cause crippling symptoms such as vertigo, visual field oscillation, and imbalance. In adult rodents, some Type II hair cells are regenerated and become re-innervated after damage, presenting opportunities for restoring vestibular function after hair cell damage. This article reviews features of vestibular sensory cells in mammals, including their basic properties, how they develop, and how they are replaced after damage. We discuss molecules that control vestibular hair cell regeneration and highlight areas in which our understanding of development and regeneration needs to be deepened. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Hair Cell Heterogeneity in the Goldfish Saccule

    NASA Technical Reports Server (NTRS)

    Saidel, William M.; Lanford, Pamela J.; Yan, Hong Y.; Popper, Arthur N.

    1995-01-01

    A set of cytological studies performed in the utricle and saccule of Astronotus ocellatus (Teleostei, Percomorphi, Cichlidae) identified two basic types of hair cells and others with some intermediate characteristics. This paper reports on applying the same techniques to the saccule of Carassius auratus (Teleostei, Otophysi, Cyprinidae) and demonstrates similar types of hair cells to those found in Astronotus. Since Carassius and Astronous are species of extreme taxonomic distance within the Euteteostei, two classes of mechanoreceptive hair cells are likely to represent the primitive condition for sensory receptors in the euteleost inner ear and perhaps in all bony fish ears.

  16. Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing Phenoxybenzamine's Potential.

    PubMed

    Majumder, Paromita; Moore, Paulette A; Richardson, Guy P; Gale, Jonathan E

    2017-01-01

    Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death. Here we used live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian hair cells in a reversible and dose-dependent manner, but pre-incubation is required for maximal inhibition of entry. We observed differential effects of phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The requirement for pre-incubation and reversibility suggests an intracellular rather than an extracellular site of action for phenoxybenzamine. We also tested the efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear explants the hair cell death resulting from 24 h exposure to neomycin was steeply dose-dependent, with 50% cell death occurring at ~230 μM for both IHC and OHC. We used 250 μM neomycin in subsequent hair-cell death assays. At 100 μM with 1 h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs and OHCs, however at higher concentrations phenoxybenzamine itself showed clear signs of ototoxicity and an additive toxic effect when combined with neomycin. These data do not

  17. Transfer characteristics of the hair cell's afferent synapse

    NASA Astrophysics Data System (ADS)

    Keen, Erica C.; Hudspeth, A. J.

    2006-04-01

    The sense of hearing depends on fast, finely graded neurotransmission at the ribbon synapses connecting hair cells to afferent nerve fibers. The processing that occurs at this first chemical synapse in the auditory pathway determines the quality and extent of the information conveyed to the central nervous system. Knowledge of the synapse's input-output function is therefore essential for understanding how auditory stimuli are encoded. To investigate the transfer function at the hair cell's synapse, we developed a preparation of the bullfrog's amphibian papilla. In the portion of this receptor organ representing stimuli of 400-800 Hz, each afferent nerve fiber forms several synaptic terminals onto one to three hair cells. By performing simultaneous voltage-clamp recordings from presynaptic hair cells and postsynaptic afferent fibers, we established that the rate of evoked vesicle release, as determined from the average postsynaptic current, depends linearly on the amplitude of the presynaptic Ca2+ current. This result implies that, for receptor potentials in the physiological range, the hair cell's synapse transmits information with high fidelity. auditory system | exocytosis | glutamate | ribbon synapse | synaptic vesicle

  18. Recent Advances in the Pathogenesis of Autoimmune Hair Loss Disease Alopecia Areata

    PubMed Central

    2013-01-01

    Alopecia areata is considered to be a cell-mediated autoimmune disease, in which autoreactive cytotoxic T cells recognize melanocyte-associated proteins such as tyrosinase. This review discusses recent advances in the understanding of the pathogenesis of alopecia areata, focusing on immunobiology and hormonal aspects of hair follicles (HFs). The HF is a unique “miniorgan” with its own immune and hormonal microenvironment. The immunosuppressive milieu of the anagen hair bulb modulated by immunosuppressive factors is known as “hair follicle immune privilege.” The collapse of the hair follicle immune privilege leads to autoimmune reactions against hair follicle autoantigens. Alopecia areata is sometimes triggered by viral infections such as influenza that causes excess production of interferons (IFN). IFN-γ is one of the key factors that lead to the collapse of immune privilege. This paper reviews the interactions between the endocrine and immune systems and hair follicles in the pathogenesis of alopecia areata. PMID:24151515

  19. Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells

    PubMed Central

    Pujol, Remy; Cunningham, Dale E.; Hailey, Dale W.; Prendergast, Andrew; Rubel, Edwin W.; Raible, David W.

    2016-01-01

    ABSTRACT Failure to form proper synapses in mechanosensory hair cells, the sensory cells responsible for hearing and balance, leads to deafness and balance disorders. Ribbons are electron-dense structures that tether synaptic vesicles to the presynaptic zone of mechanosensory hair cells where they are juxtaposed with the post-synaptic endings of afferent fibers. They are initially formed throughout the cytoplasm, and, as cells mature, ribbons translocate to the basolateral membrane of hair cells to form functional synapses. We have examined the effect of post-synaptic elements on ribbon formation and maintenance in the zebrafish lateral line system by observing mutants that lack hair cell innervation, wild-type larvae whose nerves have been transected and ribbons in regenerating hair cells. Our results demonstrate that innervation is not required for initial ribbon formation but suggest that it is crucial for regulating the number, size and localization of ribbons in maturing hair cells, and for ribbon maintenance at the mature synapse. PMID:27103160

  20. Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells.

    PubMed

    Suli, Arminda; Pujol, Remy; Cunningham, Dale E; Hailey, Dale W; Prendergast, Andrew; Rubel, Edwin W; Raible, David W

    2016-06-01

    Failure to form proper synapses in mechanosensory hair cells, the sensory cells responsible for hearing and balance, leads to deafness and balance disorders. Ribbons are electron-dense structures that tether synaptic vesicles to the presynaptic zone of mechanosensory hair cells where they are juxtaposed with the post-synaptic endings of afferent fibers. They are initially formed throughout the cytoplasm, and, as cells mature, ribbons translocate to the basolateral membrane of hair cells to form functional synapses. We have examined the effect of post-synaptic elements on ribbon formation and maintenance in the zebrafish lateral line system by observing mutants that lack hair cell innervation, wild-type larvae whose nerves have been transected and ribbons in regenerating hair cells. Our results demonstrate that innervation is not required for initial ribbon formation but suggest that it is crucial for regulating the number, size and localization of ribbons in maturing hair cells, and for ribbon maintenance at the mature synapse. © 2016. Published by The Company of Biologists Ltd.

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  3. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

    PubMed Central

    Higgins, Claire A.; Chen, James C.; Cerise, Jane E.; Jahoda, Colin A. B.; Christiano, Angela M.

    2013-01-01

    De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

  4. Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice

    PubMed Central

    Bucks, Stephanie A; Cox, Brandon C; Vlosich, Brittany A; Manning, James P; Nguyen, Tot B; Stone, Jennifer S

    2017-01-01

    Vestibular hair cells in the inner ear encode head movements and mediate the sense of balance. These cells undergo cell death and replacement (turnover) throughout life in non-mammalian vertebrates. However, there is no definitive evidence that this process occurs in mammals. We used fate-mapping and other methods to demonstrate that utricular type II vestibular hair cells undergo turnover in adult mice under normal conditions. We found that supporting cells phagocytose both type I and II hair cells. Plp1-CreERT2-expressing supporting cells replace type II hair cells. Type I hair cells are not restored by Plp1-CreERT2-expressing supporting cells or by Atoh1-CreERTM-expressing type II hair cells. Destruction of hair cells causes supporting cells to generate 6 times as many type II hair cells compared to normal conditions. These findings expand our understanding of sensorineural plasticity in adult vestibular organs and further elucidate the roles that supporting cells serve during homeostasis and after injury. DOI: http://dx.doi.org/10.7554/eLife.18128.001 PMID:28263708

  5. The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene

    PubMed Central

    Geng, Ruishuang; Melki, Sami; Chen, Daniel H.-C.; Tian, Guilian; Furness, David; Oshima-Takago, Tomoko; Neef, Jakob; Moser, Tobias; Askew, Charles; Horwitz, Geoff; Holt, Jeffrey; Imanishi, Yoshikazu; Alagramam, Kumar N.

    2012-01-01

    Mutation in the clarin-1 gene results in loss of hearing and vision in humans (Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 (Clrn1−/−) gene show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca2+ currents and membrane capacitance from IHCs that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 loading and transduction currents pointed to diminished cochlear hair bundle function in Clrn1−/− mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip-links and staircase arrangement of stereocilia were not primarily affected by Clrn1−/− mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant, p.N48K, failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p. N48K in clarin-1 (Clrn1N48K) supports our in vitro and Clrn1−/− mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Further, the ear phenotype in the Clrn1N48K mouse suggests that it is a valuable model for ear disease in CLRN1N48K, the most prevalent Usher III mutation in North America. PMID:22787034

  6. Wnt1a maintains characteristics of dermal papilla cells that induce mouse hair regeneration in a 3D preculture system.

    PubMed

    Dong, Liang; Hao, Haojie; Liu, Jiejie; Tong, Chuan; Ti, Dongdong; Chen, Deyun; Chen, Li; Li, Meirong; Liu, Huiling; Fu, Xiaobing; Han, Weidong

    2017-05-01

    Hair follicle morphogenesis and regeneration depend on intensive but well-orchestrated interactions between epithelial and mesenchymal components. Therefore, an alternative strategy to reproduce the process of epithelial-mesenchymal interaction in vitro could use a 3D system containing appropriate cell populations. The 3D air-liquid culture system for reproducibly generating hair follicles from dissociated epithelial and dermal papilla (DP) cells combined with a collagen-chitosan scaffold is described in this study. Wnt-CM was prepared from the supernatant of Wnt1a-expressing bone marrow mesenchymal stem cells (BM-MSCs) that maintain the hair-inducing gene expression of DP cells. The collagen-chitosan scaffold cells (CCS cells) were constructed using a two-step method by inoculating the Wnt-CM-treated DP cells and epidermal (EP) cells into the CCS. The cells in the air-liquid culture formed dermal condensates and a proliferative cell layer in vitro. The CCS cells were able to induce hair regeneration in nude mice. The results demonstrate that Wnt-CM can maintain the hair induction ability of DP cells in expansion cultures, and this approach can be used for large-scale preparation of CCS cells in vitro to treat hair loss. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Minocycline attenuates streptomycin-induced cochlear hair cell death by inhibiting protein nitration and poly (ADP-ribose) polymerase activation.

    PubMed

    Wang, Ping; Li, Haonan; Yu, Shuyuan; Jin, Peng; Hassan, Abdurahman; Du, Bo

    2017-08-24

    This study aimed to elucidate the protective effect of minocycline against streptomycin-induced damage of cochlear hair cells and its mechanism. Cochlear membranes were isolated from newborn Wistar rats and randomly divided into control, 500μmol/L streptomycin, 100μmol/L minocycline, and streptomycin and minocycline treatment groups. Hair cell survival was analyzed by detecting the expression of 3-nitrotyrosine (3-NT) in cochlear hair cells by immunofluorescence and an enzyme-linked immunosorbent assay. Expression of 3-NT and inducible nitric oxide synthase (iNOS), and poly (ADP-Ribose) polymerase (PARP) and caspase-3 activation were evaluated by western blotting. The results demonstrated hair cell loss at 24h after streptomycin treatment. No change was found in supporting cells of the cochleae. Minocycline pretreatment improved hair cell survival and significantly reduced the expression of iNOS and 3-NT in cochlear tissues compared with the streptomycin treatment group. PARP and caspase-3 activation was increased in the streptomycin treatment group compared with the control group, and pretreatment with minocycline decreased cleaved PARP and activated caspase-3 expression. Minocycline protected cochlear hair cells from injury caused by streptomycin in vitro. The mechanism underlying the protective effect may be associated with the inhibition of excessive formation of nitric oxide, reduction of the nitration stress reaction, and inhibition of PARP and caspase-3 activation in cochlear hair cells. Combined minocycline therapy can be applied to patients requiring streptomycin treatment. Copyright © 2017. Published by Elsevier B.V.

  8. Therapeutic strategy for hair regeneration: Hair cycle activation, niche environment modulation, wound-induced follicle neogenesis and stem cell engineering

    PubMed Central

    Chueh, Shan-Chang; Lin, Sung-Jan; Chen, Chih-Chiang; Lei, Mingxing; Wang, Ling Mei; Widelitz, Randall B.; Hughes, Michael W.; Jiang, Ting-Xing; Chuong, Cheng Ming

    2013-01-01

    Introduction There are major new advancements in the fields of stem cell biology, developmental biology, regenerative hair cycling, and tissue engineering. The time is ripe to integrate, translate and apply these findings to tissue engineering and regenerative medicine. Readers will learn about new progress in cellular and molecular aspects of hair follicle development, regeneration and potential therapeutic opportunities these advances may offer. Areas covered Here we use hair follicle formation to illustrate this progress and to identify targets for potential strategies in therapeutics. Hair regeneration is discussed in four different categories. (1) Intra-follicle regeneration (or renewal) is the basic production of hair fibers from hair stem cells and dermal papillae in existing follicles. (2) Chimeric follicles via epithelial-mesenchymal recombination to identify stem cells and signaling centers. (3) Extra-follicular factors including local dermal and systemic factors can modulate the regenerative behavior of hair follicles, and may be relatively easy therapeutic targets. (4) Follicular neogenesis means the de novo formation of new follicles. In addition, scientists are working to engineer hair follicles, which require hair forming competent epidermal cells and hair inducing dermal cells. Expert opinion Ideally self-organizing processes similar to those occurring during embryonic development should be elicited with some help from biomaterials. PMID:23289545

  9. Coenzyme Q10 protects hair cells against aminoglycoside.

    PubMed

    Sugahara, Kazuma; Hirose, Yoshinobu; Mikuriya, Takefumi; Hashimoto, Makoto; Kanagawa, Eiju; Hara, Hirotaka; Shimogori, Hiroaki; Yamashita, Hiroshi

    2014-01-01

    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.

  10. Efficacy and tolerability of Hairgain in individuals with hair loss: a placebo-controlled, double-blind study.

    PubMed

    Thom, E

    2001-01-01

    This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of a new agent for the treatment of hair loss, based on a marine protein, minerals and vitamins. Sixty subjects with hair loss of different aetiologies participated in the 6-month blinded phase of the study. Objective assessments indicated that the treatment was effective and subjective assessments showed a statistically significant positive effect of treatment. Exposure to the active preparation for a further 6 months in an open phase indicated a further improvement in hair growth. Exposure of the patients previously treated with placebo to the active preparation for 12 months gave similar results. Tolerability was good and no side-effects were reported. The product investigated may provide an alternative to pharmacotherapy for the treatment of hair-loss problems in individuals with androgenic alopecia.

  11. Gene miles-apart is required for formation of otic vesicle and hair cells in zebrafish.

    PubMed

    Hu, Z-y; Zhang, Q-y; Qin, W; Tong, J-w; Zhao, Q; Han, Y; Meng, J; Zhang, J-p

    2013-10-31

    Hearing loss is a serious burden to physical and mental health worldwide. Aberrant development and damage of hearing organs are recognized as the causes of hearing loss, the molecular mechanisms underlining these pathological processes remain elusive. Investigation of new molecular mechanisms involved in proliferation, differentiation, migration and maintenance of neuromast primordium and hair cells will contribute to better understanding of hearing loss pathology. This knowledge will enable the development of protective agents and mechanism study of drug ototoxicity. In this study, we demonstrate that the zebrafish gene miles-apart, a homolog of sphingosine-1-phosphate receptor 2 (s1pr2) in mammals, has an important role in the development of otic vesicle, neuromasts and survival of hair cells. Whole-mount in situ hybridization of embryos showed that miles-apart expression occurred mainly in the encephalic region and the somites at 24 h.p.f. (hour post fertilization), in the midbrain/hindbrain boundary, the brainstem and the pre-neuromast of lateral line at 48 h.p.f. in a strict spatiotemporal regulation. Both up- and downregulation of miles-apart led to abnormal otoliths and semicircular canals, excess or few hair cells and neuromasts, and their disarranged depositions in the lateral lines. Miles-apart (Mil) dysregulation also caused abnormal expression of hearing-associated genes, including hmx2, fgf3, fgf8a, foxi1, otop1, pax2.1 and tmieb during zebrafish organogenesis. Moreover, in larvae miles-apart gene knockdown significantly upregulated proapoptotic gene zBax2 and downregulated prosurvival gene zMcl1b; in contrast, the level of zBax2 was decreased and of zMcl1b enhanced by miles-apart overexpression. Collectively, Mil activity is linked to organization and number decision of hair cells within a neuromast, also to deposition of neuromasts and formation of otic vesicle during zebrafish organogenesis. At the larva stage, Mil as an upstream regulator of bcl-2

  12. Prestin Regulation and Function in Residual Outer Hair Cells after Noise-Induced Hearing Loss

    PubMed Central

    Xia, Anping; Song, Yohan; Wang, Rosalie; Gao, Simon S.; Clifton, Will; Raphael, Patrick; Chao, Sung-il; Pereira, Fred A.; Groves, Andrew K.; Oghalai, John S.

    2013-01-01

    The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. TectaC1509G transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9–12 kHz region), where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30–40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9–12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32–58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in order to

  13. [Morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise].

    PubMed

    2017-06-18

    To observe the morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise and to investigate the different changes in three turns of hair cells. Thirty-two healthy SD rats, all males, were randomly divided into four groups: control group, weightlessness group, noise group and weightlessness+noise groups (n=8). Then rats were exposed to -30° head down tilt as simulated weightlessness and inboard noise including steady-state noise which was (72±2) dB SPL and impulse noise up to 160 dB SPL in spaceship environment. The control group was kept in normal condition for 8 weeks. Bilateral auditory brainstem response (ABR) thresholds were tested before and after exposure respectively, and immunofluorescence staining and scanning electron microscopy (SEMs) of basilar membrane were applied after exposure. ABR threshold shifts of each group were higher after exposure. There was difference between ABRs of the experiment groups before and after exposure (P<0.05). IF showed that the inner hair cells (IHCs) missing was the main damage in the basal turn of weightlessness group, the hair cells in the middle turn were swell and in the top turn, the hair cells were not clear. In noise group, the main loss happened in the outer hair cells (OHCs) of the outermost layer. In weightlessness+noise group, the nuclear missing in the basal turn was apparent, and mainly happened at the outermost layer. Meanwhile, the missing of hair cells in the middle turn and top turn was seen at the innermost layer. SEM showed that the cilia in the basal turn of weightlessness group were serious lodging, and occasional absence. Furthermore, the basal cilia in noise group became lodged and absent, and the other two turns were seriously missing. And in weightlessness+noise group, the cilia missing in the basal turn was apparently seen. The damage degree of the four groups: weightlessness+noise group>noise group>weightlessness group>control group and the damage degree

  14. Iron deficiency in female pattern hair loss, chronic telogen effluvium, and control groups.

    PubMed

    Olsen, Elise A; Reed, Katherine B; Cacchio, Patrick B; Caudill, Leslie

    2010-12-01

    The literature suggests that iron deficiency (ID) may play a role in female pattern hair loss (FPHL) or in chronic telogen effluvium (CTE). We sought to determine if ID is more common in women with FPHL and/or CTE than in control subjects without hair loss. This was a controlled study of 381 Caucasian women aged 18 years or older with FPHL or CTE seen in the Duke University Hair Disorders Clinic, Durham, NC, and 76 Caucasian women aged 18 years or older from the university environs who had no history or physical findings of hair loss (control subjects). All participants had to have at least a serum ferritin and hemoglobin reading and history of menopausal status. When ferritin less than or equal to 15 μg/L was used as the definition, ID occurred in 12.4%, 12.1%, and 29.8% of premenopausal women with FPHL (n = 170), CTE (n = 58), and control subjects (n = 47), respectively, and in 1.7%, 10.5%, and 6.9% of postmenopausal women with FPHL (n = 115), CTE (n = 38), and control subjects (n = 29), respectively. When ferritin less than or equal to 40 μg/L was used as the definition, ID occurred in 58.8%, 63.8%, and 72.3% of premenopausal women with FPHL, CTE, and control subjects, respectively, and in 26.1%, 36.8%, and 20.7% of postmenopausal women with FPHL, CTE, and control subjects, respectively. There was no statistically significant increase in the incidence of ID in premenopausal or postmenopausal women with FPHL or CTE versus control subjects. The effect of correction of ID on hair loss is unknown. ID is common in women but not increased in patients with FPHL or CTE compared with control subjects. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  15. Usher protein functions in hair cells and photoreceptors

    PubMed Central

    Cosgrove, Dominic; Zallocchi, Marisa

    2014-01-01

    The 10 different genes associated with the deaf/blind disorder, Usher syndrome, encode a number of structurally and functionally distinct proteins, most expressed as multiple isoforms/protein variants. Functional characterization of these proteins suggests a role in stereocilia development in cochlear hair cells, likely owing to adhesive interactions in hair bundles. In mature hair cells, homodimers of the Usher cadherins, cadherin 23 and protocadherin 15, interact to form a structural fiber, the tip link, and the linkages that anchor the taller stereocilia's actin cytoskeleton core to the shorter adjacent stereocilia and the elusive mechanotransduction channels, explaining the deafness phenotype when these molecular interactions are perturbed. The conundrum is that photoreceptors lack a synonymous mechanotransduction apparatus, and so a common theory for Usher protein function in the two neurosensory cell types affected in Usher syndrome is lacking. Recent evidence linking photoreceptor cell dysfunction in the shaker 1 mouse model for Usher syndrome to light-induced protein translocation defects, combined with localization of an Usher protein interactome at the periciliary region of the photoreceptors suggests Usher proteins might regulate protein trafficking between the inner and outer segments of photoreceptors. A distinct Usher protein complex is trafficked to the ribbon synapses of hair cells, and synaptic defects have been reported in Usher mutants in both hair cells and photoreceptors. This review aims to clarify what is known about Usher protein function at the synaptic and apical poles of hair cells and photoreceptors and the prospects for identifying a unifying pathobiological mechanism to explain deaf/blindness in Usher syndrome. PMID:24239741

  16. Usher protein functions in hair cells and photoreceptors.

    PubMed

    Cosgrove, Dominic; Zallocchi, Marisa

    2014-01-01

    The 10 different genes associated with the deaf/blind disorder, Usher syndrome, encode a number of structurally and functionally distinct proteins, most expressed as multiple isoforms/protein variants. Functional characterization of these proteins suggests a role in stereocilia development in cochlear hair cells, likely owing to adhesive interactions in hair bundles. In mature hair cells, homodimers of the Usher cadherins, cadherin 23 and protocadherin 15, interact to form a structural fiber, the tip link, and the linkages that anchor the taller stereocilia's actin cytoskeleton core to the shorter adjacent stereocilia and the elusive mechanotransduction channels, explaining the deafness phenotype when these molecular interactions are perturbed. The conundrum is that photoreceptors lack a synonymous mechanotransduction apparatus, and so a common theory for Usher protein function in the two neurosensory cell types affected in Usher syndrome is lacking. Recent evidence linking photoreceptor cell dysfunction in the shaker 1 mouse model for Usher syndrome to light-induced protein translocation defects, combined with localization of an Usher protein interactome at the periciliary region of the photoreceptors suggests Usher proteins might regulate protein trafficking between the inner and outer segments of photoreceptors. A distinct Usher protein complex is trafficked to the ribbon synapses of hair cells, and synaptic defects have been reported in Usher mutants in both hair cells and photoreceptors. This review aims to clarify what is known about Usher protein function at the synaptic and apical poles of hair cells and photoreceptors and the prospects for identifying a unifying pathobiological mechanism to explain deaf/blindness in Usher syndrome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Mechanosensory hair cells express two molecularly distinct mechanotransduction channels

    PubMed Central

    Zhao, Bo; Cunningham, Christopher; Harkins-Perry, Sarah; Coste, Bertrand; Ranade, Sanjeev; Zebarjadi, Navid; Beurg, Maryline; Fettiplace, Robert; Patapoutian, Ardem; Mueller, Ulrich

    2016-01-01

    Auditory hair cells contain mechanotransduction channels that rapidly open in response to sound-induced vibrations. Surprisingly, we report here that auditory hair cells contain two molecularly distinct mechanotransduction channels. One ion channel is activated by sound and is responsible for sensory transduction. This sensory transduction channel is expressed in hair-cell stereocilia and previous studies show that its activity is affected by mutations in the genes encoding the transmembrane proteins TMHS/LHFPL5, TMIE and TMC1/2. We show here that the second ion channel is expressed at the apical surface of hair cells and contains the Piezo2 protein. The activity of the Piezo2-dependent channel is controlled by the intracellular Ca2+ concentration and can be recorded following disruption of the sensory transduction machinery or more generally by disruption of the sensory epithelium. We thus conclude that hair cells express two molecularly and functionally distinct mechanotransduction channels with different subcellular distribution. PMID:27893727

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

    NASA Technical Reports Server (NTRS)

    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.

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

    PubMed Central

    Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

    2014-01-01

    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. PMID:25383178

  20. Voltage-Gated Calcium Influx Modifies Cholinergic Inhibition of Inner Hair Cells in the Immature Rat Cochlea.

    PubMed

    Zachary, Stephen; Nowak, Nathaniel; Vyas, Pankhuri; Bonanni, Luke; Fuchs, Paul Albert

    2018-06-20

    Until postnatal day (P) 12, inner hair cells of the rat cochlea are invested with both afferent and efferent synaptic connections. With the onset of hearing at P12, the efferent synapses disappear, and afferent (ribbon) synapses operate with greater efficiency. This change coincides with increased expression of voltage-gated potassium channels, the loss of calcium-dependent electrogenesis, and the onset of graded receptor potentials driven by sound. The transient efferent synapses include near-membrane postsynaptic cisterns thought to regulate calcium influx through the hair cell's α9-containing and α10-containing nicotinic acetylcholine receptors. This influx activates small-conductance Ca 2+ -activated K + (SK) channels. Serial-section electron microscopy of inner hair cells from two 9-d-old (male) rat pups revealed many postsynaptic efferent cisterns and presynaptic afferent ribbons whose average minimal separation in five cells ranged from 1.1 to 1.7 μm. Efferent synaptic function was studied in rat pups (age, 7-9 d) of either sex. The duration of these SK channel-mediated IPSCs was increased by enhanced calcium influx through L-type voltage-gated channels, combined with ryanodine-sensitive release from internal stores-presumably the near-membrane postsynaptic cistern. These data support the possibility that inner hair cell calcium electrogenesis modulates the efficacy of efferent inhibition during the maturation of inner hair cell synapses. SIGNIFICANCE STATEMENT Strict calcium buffering is essential for cellular function. This problem is especially acute for compact hair cells where increasing cytoplasmic calcium promotes the opposing functions of closely adjoining afferent and efferent synapses. The near-membrane postsynaptic cistern at efferent synapses segregates synaptic calcium signals by acting as a dynamic calcium store. The hair cell serves as an informative model for synapses with postsynaptic cisterns (C synapses) found in central neurons

  1. Hair shafts in trichoscopy: clues for diagnosis of hair and scalp diseases.

    PubMed

    Rudnicka, Lidia; Rakowska, Adriana; Kerzeja, Marta; Olszewska, Małgorzata

    2013-10-01

    Trichoscopy (hair and scalp dermoscopy) analyzes the structure and size of growing hair shafts, providing diagnostic clues for inherited and acquired causes of hair loss. Types of hair shaft abnormalities observed include exclamation mark hairs (alopecia areata, trichotillomania, chemotherapy-induced alopecia), Pohl-Pinkus constrictions (alopecia areata, chemotherapy-induced alopecia, blood loss, malnutrition), comma hairs (tinea capitis), corkscrew hairs (tinea capitis), coiled hairs (trichotillomania), flame hairs (trichotillomania), and tulip hairs (in trichotillomania, alopecia areata). Trichoscopy allows differential diagnosis of most genetic hair shaft disorders. This article proposes a classification of hair shaft abnormalities observed by trichoscopy. Copyright © 2013. Published by Elsevier Inc.

  2. Structure and Function of the Hair Cell Ribbon Synapse

    PubMed Central

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

    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 cell afferent synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years. PMID:16773499

  3. The molecular basis of neurosensory cell formation in ear development: a blueprint for hair cell and sensory neuron regeneration?

    PubMed Central

    Fritzsch, Bernd; Beisel, Kirk W.; Hansen, Laura

    2014-01-01

    Summary The inner ear of mammals uses neurosensory cells derived from the embryonic ear for mechanoelectric transduction of vestibular and auditory stimuli (the hair cells) and conducts this information to the brain via sensory neurons. As with most other neurons of mammals, lost hair cells and sensory neurons are not spontaneously replaced and result instead in age-dependent progressive hearing loss. We review the molecular basis of neurosensory development in the mouse ear to provide a blueprint for possible enhancement of therapeutically useful transformation of stem cells into lost neurosensory cells. We identify several readily available adult sources of stem cells that express, like the ectoderm-derived ear, genes known to be essential for ear development. Use of these stem cells combined with molecular insights into neurosensory cell specification and proliferation regulation of the ear, might allow for neurosensory regeneration of mammalian ears in the near future. PMID:17120192

  4. Stem cell dynamics in the hair follicle niche

    PubMed Central

    Rompolas, Panteleimon; Greco, Valentina

    2014-01-01

    Hair follicles are skin appendages of the mammalian skin that have the ability to periodically and stereotypically regenerate in order to continuously produce new hair over our lifetime. The ability of the hair follicle to regenerate is due to the presence of stem cells that along with other cell populations and non-cellular components, including molecular signals and extracellular material, make up a niche microenvironment. Mounting evidence suggests that the niche is critical for regulating stem cell behavior and thus the process of regeneration. Here we review the literature concerning past and current studies that have utilized mouse genetic models, combined with other approaches to dissect the molecular and cellular composition of the hair follicle niche. We also discuss our current understanding of how stem cells operate within the niche during the process of tissue regeneration and the factors that regulate their behavior. PMID:24361866

  5. The biology, structure, and function of eyebrow hair.

    PubMed

    Nguyen, Jennifer V

    2014-01-01

    Eyebrow hair serves many important biologic and aesthetic functions. This article reviews the structure and function of the hair follicle, as well as hair follicle morphogenesis and cycling. Eyebrow hair follicles share the same basic structure as hair follicles elsewhere on the body, but are distinguished by their shorter anagen (growing) phase. Knowledge of the hair follicle structure and cycle is important for understanding the pathophysiology of alopecia, as diseases affecting the stem cell portion of the hair follicle in the bulge region may cause permanent hair loss. Furthermore, therapeutic agents that target distinct phases and hormones involved in the hair cycle may be useful for promoting hair growth.

  6. β-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche.

    PubMed

    Deschene, Elizabeth R; Myung, Peggy; Rompolas, Panteleimon; Zito, Giovanni; Sun, Thomas Yang; Taketo, Makoto M; Saotome, Ichiko; Greco, Valentina

    2014-03-21

    Wnt/β-catenin signaling is critical for tissue regeneration. However, it is unclear how β-catenin controls stem cell behaviors to coordinate organized growth. Using live imaging, we show that activation of β-catenin specifically within mouse hair follicle stem cells generates new hair growth through oriented cell divisions and cellular displacement. β-Catenin activation is sufficient to induce hair growth independently of mesenchymal dermal papilla niche signals normally required for hair regeneration. Wild-type cells are co-opted into new hair growths by β-catenin mutant cells, which non-cell autonomously activate Wnt signaling within the neighboring wild-type cells via Wnt ligands. This study demonstrates a mechanism by which Wnt/β-catenin signaling controls stem cell-dependent tissue growth non-cell autonomously and advances our understanding of the mechanisms that drive coordinated regeneration.

  7. Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis.

    PubMed

    Lee, Soung-Hoon; Seo, Seol Hwa; Lee, Dong-Hwan; Pi, Long-Quan; Lee, Won-Soo; Choi, Kang-Yell

    2017-11-01

    The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair regrowth and wound-induced hair follicle neogenesis via an interaction with Dishevelled. CXXC5 was upregulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells. Moreover, CXXC5 -/- mice displayed accelerated hair regrowth, and treatment with valproic acid, a glycogen synthase kinase 3β inhibitor that activates the Wnt/β-catenin pathway, further induced hair regrowth in the CXXC5 -/- mice. Disrupting the CXXC5-Dishevelled interaction with a competitor peptide activated the Wnt/β-catenin pathway and accelerated hair regrowth and wound-induced hair follicle neogenesis. Overall, these findings suggest that the CXXC5-Dishevelled interaction is a potential target for the treatment of hair loss. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. A Marine Protein-based Dietary Supplement for Subclinical Hair Thinning/Loss: Results of a Multisite, Double-blind, Placebo-controlled Clinical Trial

    PubMed Central

    Rizer, Ronald L; Stephens, Thomas J; Herndon, James H; Sperber, Brian R; Murphy, James; Ablon, Glynis R

    2015-01-01

    Introduction: Since skin and hair quality are potent vitality signals, and hair growth deficiency can cause significant psychological morbidity. In addition to clearly-defined hair loss disorders, milder forms of hair thinning or hair loss appear to be increasingly common, with a suggestion that sub-optimal diets and stressful lifestyles may be involved. Methods: Here we assess the value of a dietary marine-extract based dietary supplement in premenopausal women with subclinical hair thinning or hair loss conditions. This multi-site, randomized double-blind, placebo-controlled clinical trial was conducted with impact on hair shedding rate and hair fiber diameter (assessed by phototrichogram) as primary end points upon consumption of the oral supplement compared to a placebo. A total of 96 eligible female subjects were enrolled aged 21–55 years of age from Asian, Caucasian, and Hispanic ethnic backgrounds. Results: This study showed that hair shedding was significantly reduced in the first 3–6 months of daily consumption of the oral supplement. Moreover, phototrichogram image analysis revealed a statistically significant increase in the mean vellus-like hair diameter after 6 months of supplement consumption, when compared to the mean vellus-like hair diameters measured at baseline. Discussion: These results support the view that a nutritional supplement approach may be useful for women in this age group to deal with subclinical hair thinning or hair loss conditions, and those components of this marine extract-based oral supplement may be a useful adjunct. PMID:26903744

  9. Wnt Responsive Lgr5-Expressing Stem Cells Are Hair Cell Progenitors in the Cochlea

    PubMed Central

    Shi, Fuxin; Kempfle, Judith; Edge, Albert S. B.

    2012-01-01

    Auditory hair cells are surrounded on their basolateral aspects by supporting cells, and these two cell types together constitute the sensory epithelium of the organ of Corti, which is the hearing apparatus of the ear. We show here that Lgr5, a marker for adult stem cells, was expressed in a subset of supporting cells in the newborn and adult murine cochlea. Lgr5-expressing supporting cells, sorted by flow cytometry and cultured in a single cell suspension, as compared to unsorted cells, displayed an enhanced capacity for self-renewing neurosphere formation in response to Wnt and were converted to hair cells at a higher (>10-fold) rate. The greater differentiation of hair cell in the neurosphere assay showed that Lgr5-positive cells had the capacity to act as cochlear progenitor cells, and lineage tracing confirmed that Lgr5-expressing cells accounted for the cells that formed neurospheres and differentiated to hair cells. The responsiveness to Wnt of cells with a capacity for division and sensory cell formation suggests a potential route to new hair cell generation in the adult cochlea. PMID:22787049

  10. Melatonin mitigates neomycin-induced hair cell injury in zebrafish.

    PubMed

    Oh, Kyoung Ho; Rah, Yoon Chan; Hwang, Kyu Ho; Lee, Seung Hoon; Kwon, Soon Young; Cha, Jae Hyung; Choi, June

    2017-10-01

    Ototoxicity due to medications, such as aminoglycosides, is irreversible, and free radicals in the inner ear are assumed to play a major role. Because melatonin has an antioxidant property, we hypothesize that it might mitigate hair cell injury by aminoglycosides. The objective of this study was to evaluate whether melatonin has an alleviative effect on neomycin-induced hair cell injury in zebrafish (Danio rerio). Various concentrations of melatonin were administered to 5-day post-fertilization zebrafish treated with 125 μM neomycin for 1 h. Surviving hair cells within four neuromasts were compared with that of a control group. Apoptosis was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The changes of ultrastructure were confirmed using a scanning electron microscope. Melatonin alleviated neomycin-induced hair cell injury in neuromasts (neomycin + melatonin 100 μM: 13.88 ± 0.91 cells, neomycin only: 7.85 ± 0.90 cells; n = 10, p < 0.05) and reduced neomycin-induced apoptosis in the TUNEL assay. In ultrastructural analysis, hair cells within the neuromasts in zebrafish were preserved exposed to 125 μM neomycin and 100 μM melatonin for 1 h in SEM findings. Melatonin is effective in alleviating aminoglycoside-induced hair cell injury in zebrafish. The results of this study demonstrated that melatonin has the potential to reduce apoptosis induced by aminoglycosides in zebrafish.

  11. Use of Vitamins and Minerals in the Treatment of Hair Loss: A Cross-Sectional Survey among Dermatologists in Saudi Arabia.

    PubMed

    Mubki, Thamer

    2014-11-01

    Several controversies exist regarding the use of vitamin and mineral supplements in treating hair loss. To explore practices, knowledge, and attitudes for using vitamins and minerals in treating hair loss among dermatologists in Saudi Arabia. A self-administrated questionnaire containing 33 questions was distributed to 177 dermatologists attending a national dermatology conference in Riyadh, Saudi Arabia, in 2012. Of the 177 attending dermatologists, 144 responded to the questionnaire (81% response rate). Vitamins and minerals were recommended for treating at least one type of hair loss by 60%. Vitamins and minerals were most commonly used for acute telogen effluvium (62%). The majority (72%) reported a good knowledge of vitamins and minerals toxicity. Although dermatologists in Saudi Arabia displayed positive believes in the usefulness of vitamins and minerals in treating hair loss, further research is needed to prove their role in the management of different hair loss disorders.

  12. A new technique for quantitative analysis of hair loss in mice using grayscale analysis.

    PubMed

    Ponnapakkam, Tulasi; Katikaneni, Ranjitha; Gulati, Rohan; Gensure, Robert

    2015-03-09

    Alopecia is a common form of hair loss which can occur in many different conditions, including male-pattern hair loss, polycystic ovarian syndrome, and alopecia areata. Alopecia can also occur as a side effect of chemotherapy in cancer patients. In this study, our goal was to develop a consistent and reliable method to quantify hair loss in mice, which will allow investigators to accurately assess and compare new therapeutic approaches for these various forms of alopecia. The method utilizes a standard gel imager to obtain and process images of mice, measuring the light absorption, which occurs in rough proportion to the amount of black (or gray) hair on the mouse. Data that has been quantified in this fashion can then be analyzed using standard statistical techniques (i.e., ANOVA, T-test). This methodology was tested in mouse models of chemotherapy-induced alopecia, alopecia areata and alopecia from waxing. In this report, the detailed protocol is presented for performing these measurements, including validation data from C57BL/6 and C3H/HeJ strains of mice. This new technique offers a number of advantages, including relative simplicity of application, reliance on equipment which is readily available in most research laboratories, and applying an objective, quantitative assessment which is more robust than subjective evaluations. Improvements in quantification of hair growth in mice will improve study of alopecia models and facilitate evaluation of promising new therapies in preclinical studies.

  13. Repair of traumatized mammalian hair cells via sea anemone repair proteins.

    PubMed

    Tang, Pei-Ciao; Smith, Karen Müller; Watson, Glen M

    2016-08-01

    Mammalian hair cells possess only a limited ability to repair damage after trauma. In contrast, sea anemones show a marked capability to repair damaged hair bundles by means of secreted repair proteins (RPs). Previously, it was found that recovery of traumatized hair cells in blind cavefish was enhanced by anemone-derived RPs; therefore, the ability of anemone RPs to assist recovery of damaged hair cells in mammals was tested here. After a 1 h incubation in RP-enriched culture media, uptake of FM1-43 by experimentally traumatized murine cochlear hair cells was restored to levels comparable to those exhibited by healthy controls. In addition, RP-treated explants had significantly more normally structured hair bundles than time-matched traumatized control explants. Collectively, these results indicate that anemone-derived RPs assist in restoring normal function and structure of experimentally traumatized hair cells of the mouse cochlea. © 2016. Published by The Company of Biologists Ltd.

  14. Steady-state stiffness of utricular hair cells depends on macular location and hair bundle structure.

    PubMed

    Spoon, Corrie; Moravec, W J; Rowe, M H; Grant, J W; Peterson, E H

    2011-12-01

    Spatial and temporal properties of head movement are encoded by vestibular hair cells in the inner ear. One of the most striking features of these receptors is the orderly structural variation in their mechanoreceptive hair bundles, but the functional significance of this diversity is poorly understood. We tested the hypothesis that hair bundle structure is a significant contributor to hair bundle mechanics by comparing structure and steady-state stiffness of 73 hair bundles at varying locations on the utricular macula. Our first major finding is that stiffness of utricular hair bundles varies systematically with macular locus. Stiffness values are highest in the striola, near the line of hair bundle polarity reversal, and decline exponentially toward the medial extrastriola. Striolar bundles are significantly more stiff than those in medial (median: 8.9 μN/m) and lateral (2.0 μN/m) extrastriolae. Within the striola, bundle stiffness is greatest in zone 2 (106.4 μN/m), a band of type II hair cells, and significantly less in zone 3 (30.6 μN/m), which contains the only type I hair cells in the macula. Bathing bundles in media that break interciliary links produced changes in bundle stiffness with predictable time course and magnitude, suggesting that links were intact in our standard media and contributed normally to bundle stiffness during measurements. Our second major finding is that bundle structure is a significant predictor of steady-state stiffness: the heights of kinocilia and the tallest stereocilia are the most important determinants of bundle stiffness. Our results suggest 1) a functional interpretation of bundle height variability in vertebrate vestibular organs, 2) a role for the striola in detecting onset of head movement, and 3) the hypothesis that differences in bundle stiffness contribute to diversity in afferent response dynamics.

  15. Steady-state stiffness of utricular hair cells depends on macular location and hair bundle structure

    PubMed Central

    Spoon, Corrie; Moravec, W. J.; Rowe, M. H.; Grant, J. W.

    2011-01-01

    Spatial and temporal properties of head movement are encoded by vestibular hair cells in the inner ear. One of the most striking features of these receptors is the orderly structural variation in their mechanoreceptive hair bundles, but the functional significance of this diversity is poorly understood. We tested the hypothesis that hair bundle structure is a significant contributor to hair bundle mechanics by comparing structure and steady-state stiffness of 73 hair bundles at varying locations on the utricular macula. Our first major finding is that stiffness of utricular hair bundles varies systematically with macular locus. Stiffness values are highest in the striola, near the line of hair bundle polarity reversal, and decline exponentially toward the medial extrastriola. Striolar bundles are significantly more stiff than those in medial (median: 8.9 μN/m) and lateral (2.0 μN/m) extrastriolae. Within the striola, bundle stiffness is greatest in zone 2 (106.4 μN/m), a band of type II hair cells, and significantly less in zone 3 (30.6 μN/m), which contains the only type I hair cells in the macula. Bathing bundles in media that break interciliary links produced changes in bundle stiffness with predictable time course and magnitude, suggesting that links were intact in our standard media and contributed normally to bundle stiffness during measurements. Our second major finding is that bundle structure is a significant predictor of steady-state stiffness: the heights of kinocilia and the tallest stereocilia are the most important determinants of bundle stiffness. Our results suggest 1) a functional interpretation of bundle height variability in vertebrate vestibular organs, 2) a role for the striola in detecting onset of head movement, and 3) the hypothesis that differences in bundle stiffness contribute to diversity in afferent response dynamics. PMID:21918003

  16. Defective calmodulin-dependent rapid apical endocytosis in zebrafish sensory hair cell mutants.

    PubMed

    Seiler, C; Nicolson, T

    1999-11-15

    Vertebrate mechanosensory hair cells contain a narrow "pericuticular" zone which is densely populated with small vesicles between the cuticular plate and cellular junctions near the apical surface. The presence of many cytoplasmic vesicles suggests that the apical surface of hair cells has a high turnover rate. The significance of intense membrane trafficking at the apical surface is not known. Using a marker of endocytosis, the styryl dye FM1-43, this report shows that rapid apical endocytosis in zebrafish lateral line sensory hair cells is calcium and calmodulin dependent and is partially blocked by the presence of amiloride and dihydrostreptomycin, known inhibitors of mechanotransduction channels. As seen in lateral line hair cells, sensory hair cells within the larval otic capsule also exhibit rapid apical endocytosis. Defects in internalization of the dye in both lateral line and inner ear hair cells were found in five zebrafish auditory/vestibular mutants: sputnik, mariner, orbiter, mercury, and skylab. In addition, lateral line hair cells in these mutants were not sensitive to prolonged exposure to streptomycin, which is toxic to hair cells. The presence of endocytic defects in the majority of zebrafish mechanosensory mutants points to a important role of apical endocytosis in hair cell function. Copyright 1999 John Wiley & Sons, Inc.

  17. Frontal fibrosing alopecia associated with generalized hair loss.

    PubMed

    Armenores, Paul; Shirato, Kyoko; Reid, Catherine; Sidhu, Shireen

    2010-08-01

    We present six cases of frontal fibrosing alopecia, in which generalized hair loss is a feature. Although this variant of lichen planopilaris has been reported clinically in a number of patients, there is very little histological evidence that the condition exists in peripheral sites. We believe this pattern of involvement may be more common than is reported, and have provided histological evidence of lichen planopilaris being present at sites beyond the scalp and eyebrows.

  18. The goya mouse mutant reveals distinct newly identified roles for MAP3K1 in the development and survival of cochlear sensory hair cells.

    PubMed

    Parker, Andrew; Cross, Sally H; Jackson, Ian J; Hardisty-Hughes, Rachel; Morse, Susan; Nicholson, George; Coghill, Emma; Bowl, Michael R; Brown, Steve D M

    2015-12-01

    Mitogen-activated protein kinase, MAP3K1, plays an important role in a number of cellular processes, including epithelial migration during eye organogenesis. In addition, studies in keratinocytes indicate that MAP3K1 signalling through JNK is important for actin stress fibre formation and cell migration. However, MAP3K1 can also act independently of JNK in the regulation of cell proliferation and apoptosis. We have identified a mouse mutant, goya, which exhibits the eyes-open-at-birth and microphthalmia phenotypes. In addition, these mice also have hearing loss. The goya mice carry a splice site mutation in the Map3k1 gene. We show that goya and kinase-deficient Map3k1 homozygotes initially develop supernumerary cochlear outer hair cells (OHCs) that subsequently degenerate, and a progressive profound hearing loss is observed by 9 weeks of age. Heterozygote mice also develop supernumerary OHCs, but no cellular degeneration or hearing loss is observed. MAP3K1 is expressed in a number of inner-ear cell types, including outer and inner hair cells, stria vascularis and spiral ganglion. Investigation of targets downstream of MAP3K1 identified an increase in p38 phosphorylation (Thr180/Tyr182) in multiple cochlear tissues. We also show that the extra OHCs do not arise from aberrant control of proliferation via p27KIP1. The identification of the goya mutant reveals a signalling molecule involved with hair-cell development and survival. Mammalian hair cells do not have the ability to regenerate after damage, which can lead to irreversible sensorineural hearing loss. Given the observed goya phenotype, and the many diverse cellular processes that MAP3K1 is known to act upon, further investigation of this model might help to elaborate upon the mechanisms underlying sensory hair cell specification, and pathways important for their survival. In addition, MAP3K1 is revealed as a new candidate gene for human sensorineural hearing loss. © 2015. Published by The Company of

  19. The electrical properties of auditory hair cells in the frog amphibian papilla.

    PubMed

    Smotherman, M S; Narins, P M

    1999-07-01

    The amphibian papilla (AP) is the principal auditory organ of the frog. Anatomical and neurophysiological evidence suggests that this hearing organ utilizes both mechanical and electrical (hair cell-based) frequency tuning mechanisms, yet relatively little is known about the electrophysiology of AP hair cells. Using the whole-cell patch-clamp technique, we have investigated the electrical properties and ionic currents of isolated hair cells along the rostrocaudal axis of the AP. Electrical resonances were observed in the voltage response of hair cells harvested from the rostral and medial, but not caudal, regions of the AP. Two ionic currents, ICa and IK(Ca), were observed in every hair cell; however, their amplitudes varied substantially along the epithelium. Only rostral hair cells exhibited an inactivating potassium current (IA), whereas an inwardly rectifying potassium current (IK1) was identified only in caudal AP hair cells. Electrically tuned hair cells exhibited resonant frequencies from 50 to 375 Hz, which correlated well with hair cell position and the tonotopic organization of the papilla. Variations in the kinetics of the outward current contribute substantially to the determination of resonant frequency. ICa and IK(Ca) amplitudes increased with resonant frequency, reducing the membrane time constant with increasing resonant frequency. We conclude that a tonotopically organized hair cell substrate exists to support electrical tuning in the rostromedial region of the frog amphibian papilla and that the cellular mechanisms for frequency determination are very similar to those reported for another electrically tuned auditory organ, the turtle basilar papilla.

  20. Dexamethasone protects auditory hair cells against TNFalpha-initiated apoptosis via activation of PI3K/Akt and NFkappaB signaling.

    PubMed

    Haake, Scott M; Dinh, Christine T; Chen, Shibing; Eshraghi, Adrien A; Van De Water, Thomas R

    2009-09-01

    Tumor necrosis factor alpha (TNFalpha) is associated with trauma-induced hearing loss. Local treatment of cochleae of trauma-exposed animals with a glucocorticoid is effective in reducing the level of hearing loss that occurs post-trauma (e.g., electrode insertion trauma-induced hearing loss/dexamethasone treatment). Dexamethasone (Dex) protects auditory hair cells (AHCs) from trauma-induced loss by activating cellular signal pathways that promote cell survival. Organ of Corti explants challenged with an ototoxic level of TNFalpha was the trauma model with Dex the otoprotective drug. A series of inhibitors were used in combination with the Dex treatment of TNFalpha-exposed explants to investigate the signal molecules that participate in Dex-mediated otoprotection. The otoprotective capacity of Dex against TNFalpha ototoxicity was determined by hair cell counts obtained from fixed explants stained with FITC-phalloidin labeling with investigators blinded to specimen identity. The general caspase inhibitor Boc-d-fmk prevented TNFalpha-induced AHC death. There was a significant reduction (p<0.05) in the efficacy of Dex otoprotection against TNFalpha ototoxicity when the following cellular events were blocked: (1) glucocorticoid receptors (Mif); (2) PI3K (LY294002); (3) Akt/PKB (SH-6); and (4) NFkappaB (NFkappaB-I). Dex treatment protects hair cells against TNFalpha apoptosis in vitro by activation of PI3K/Akt and NFkappaB signaling.

  1. Titrated extract of Centella asiatica increases hair inductive property through inhibition of STAT signaling pathway in three-dimensional spheroid cultured human dermal papilla cells.

    PubMed

    Choi, Yeong Min; An, Sungkwan; Lee, Junwoo; Lee, Jae Ho; Lee, Jae Nam; Kim, Young Sam; Ahn, Kyu Joong; An, In-Sook; Bae, Seunghee

    2017-12-01

    Dermal papilla (DP) is a pivotal part of hair follicle, and the smaller size of the DP is related with the hair loss. In this study, we investigated the effect of titrated extract of Centella asiatica (TECA) on hair growth inductive property on 3D spheroid cultured human DP cells (HDP cells). Significantly increased effect of TECA on cell viability was only shown in 3D sphered HPD cells, not in 2D cultured HDP cells. Also, TECA treatment increased the sphere size of HDP cells. The luciferase activity of STAT reporter genes and the expression of STAT-targeted genes, SOCS1 and SOCS3, were significantly decreased. Also, TECA treatment increased the expression of the hair growth-related signature genes in 3D sphered HDP cells. Furthermore, TECA led to downregulation of the level of phosphorylated STAT proteins in 3D sphered HDP cells. Overall, TECA activates the potential of hair inductive capacity in HDP cells.

  2. Influence of leisure-time noise on outer hair cell activity in medical students.

    PubMed

    Rosanowski, Frank; Eysholdt, Ulrich; Hoppe, Ulrich

    2006-10-01

    Noise exceeding a certain level can damage outer hair cells and thus cause hearing loss. In the past, noise-induced hearing loss was mainly caused by occupational noise. Leisure-time noise may be a promoting factor, particularly in young adults. The purpose of this study was to investigate whether transient evoked otoacoustic emissions (TEOAE) can be used to evaluate outer hair cell damage in young adults with no history of hearing complaints. The data obtained from the measurement of TEOAE were correlated with the participants' listening habits and exposure to leisure-time noise. Eighty-eight young adults (47 women, 41 men; age 22.9+/-2.9 years) were examined. TEOAE were measured using standard ILO 88 equipment. All participants had normal hearing (hearing thresholds better than 20 dB HL; frequency range 0.125-10 kHz). None of the participants suffered from permanent tinnitus. All participants answered a questionnaire concerning their listening habits. On average, the participants frequented a discotheque 1.4 times a month; 25% had never visited a discotheque, 35% visited once a month and 32% twice or three times a month. Sixteen per cent reported transient tinnitus after every visit to a discotheque and 58% after nearly every visit. Eight per cent suffered from transient hearing loss after every visit to a disco and 37% after nearly every visit. Three per cent (4%) reported tinnitus (nearly) every morning after visiting a discotheque. The TEOAE level was above 6 dB in all participants [9.2+/-3.6 dB (mean +/- SD)] and reproducibility was above 60% (90+/-9%). All values matched pass criteria for normal TEOAE under clinical conditions. However, TEOAE levels and reproducibility decreased significantly with an increased number of visits to discotheques. Outer hair cell damage could be measured using TEOAE in individuals exposed to leisure-time noise, although these individuals exhibited no measurable puretone hearing loss.

  3. Female pattern hair loss: a pilot study investigating combination therapy with low-dose oral minoxidil and spironolactone.

    PubMed

    Sinclair, Rodney D

    2018-01-01

    Minoxidil and spironolactone are oral antihypertensives known to stimulate hair growth. To report on a case series of women with pattern hair loss (PHL) treated with once daily minoxidil 0.25 mg and spironolactone 25 mg. Women newly diagnosed with a Sinclair stage 2-5 PHL were scored for hair shedding and hair density before and after 12 months of treatment with oral minoxidil 0.25 mg and spironolactone 25 mg. A total of 100 women were included in this observational pilot study. Mean age was 48.44 years (range 18-80). Mean hair loss severity at baseline was Sinclair 2.79 (range 2-5). Mean hair shedding score at baseline was 4.82. Mean duration of diagnosis was 6.5 years (range 0.5-30). Mean reduction in hair loss severity score was 0.85 at 6 months and 1.3 at 12 months. Mean reduction in hair shedding score was 2.3 at 6 months and 2.6 at 12 months. Mean change in blood pressure was -4.52 mmHg systolic and -6.48 mmHg diastolic. Side effects were seen in eight women but were generally mild. No patients developed hyperkalemia or any other blood test abnormality. Six of these women continued treatment, and two women who developed urticaria discontinued treatment. Prospective, uncontrolled, open-label observational study. Once daily capsules containing minoxidil 0.25 mg and spironolactone 25 mg appear to be safe and effective in the treatment of FPHL. Placebo-controlled studies to investigate this further are warranted. © 2017 The International Society of Dermatology.

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

    PubMed

    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.

  5. Efficacy and safety of 5% minoxidil topical foam in male pattern hair loss treatment and patient satisfaction.

    PubMed

    Hasanzadeh, Hournaz; Nasrollahi, Saman Ahmad; Halavati, Nader; Saberi, Maryam; Firooz, Alireza

    2016-09-01

    Male pattern hair loss is widespread around the world. Its prevalence indicates the importance of finding the best treatment modalities. This study evaluates the efficacy and safety of minoxidil 5% topical foam in male pattern hair loss treatment and patient satisfaction. This study was a before-and-after trial on 17 male patients with male pattern hair loss. Subjects were instructed to apply one capful (1 ml) of minoxidil 5% topical foam on the scalp daily for 6 months. Efficacy was assessed through hair counts, subject assessment, and global photographic review. Seventeen male volunteers were recruited, and three volunteers were withdrawn; 14 participated in the trial for 16 weeks, and 12 continued up to 24 weeks. The average hair count with a camera at week 16 (181.87 ± 52.42) and week 24 (194.58 ± 62.82) and with an eye count at week 16 (62.57 ± 15.28) and week 24 (69.91 ± 15.61) increased significantly compared to the baseline after intervention. This study confirmed that minoxidil 5% topical foam is a safe and effective treatment for MPHL. The effect of it is evident after 24 weeks of use.

  6. Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment.

    PubMed

    Ponnath, Abhilash; Depreux, Frederic F; Jodelka, Francine M; Rigo, Frank; Farris, Hamilton E; Hastings, Michelle L; Lentz, Jennifer J

    2018-02-01

    The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.

  7. Static length changes of cochlear outer hair cells can tune low-frequency hearing

    PubMed Central

    Ciganović, Nikola; Warren, Rebecca L.; Keçeli, Batu; Jacob, Stefan

    2018-01-01

    The cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti. We develop a geometry-based kinematic model of the apical organ of Corti that reproduces salient, yet counter-intuitive features of the organ’s motion. Our analysis further uncovers a mechanism by which a static length change of the outer hair cells can sensitively tune the signal transmitted to the sensory inner hair cells. When the outer hair cells are in an elongated state, stimulation of inner hair cells is largely inhibited, whereas outer hair cell contraction leads to a substantial enhancement of sound-evoked motion near the hair bundles. This novel mechanism for regulating the sensitivity of the hearing organ applies to the low frequencies that are most important for the perception of speech and music. We suggest that the proposed mechanism might underlie frequency discrimination at low auditory frequencies, as well as our ability to selectively attend auditory signals in noisy surroundings. PMID:29351276

  8. [Hormones and hair growth].

    PubMed

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

  9. Genetic analysis of vertebrate sensory hair cell mechanosensation: the zebrafish circler mutants.

    PubMed

    Nicolson, T; Rüsch, A; Friedrich, R W; Granato, M; Ruppersberg, J P; Nüsslein-Volhard, C

    1998-02-01

    The molecular basis of sensory hair cell mechanotransduction is largely unknown. In order to identify genes that are essential for mechanosensory hair cell function, we characterized a group of recently isolated zebrafish motility mutants. These mutants are defective in balance and swim in circles but have no obvious morphological defects. We examined the mutants using calcium imaging of acoustic-vibrational and tactile escape responses, high resolution microscopy of sensory neuroepithelia in live larvae, and recordings of extracellular hair cell potentials (microphonics). Based on the analyses, we have identified several classes of genes. Mutations in sputnik and mariner affect hair bundle integrity. Mutant astronaut and cosmonaut hair cells have relatively normal microphonics and thus appear to affect events downstream of mechanotransduction. Mutant orbiter, mercury, and gemini larvae have normal hair cell morphology and yet do not respond to acoustic-vibrational stimuli. The microphonics of lateral line hair cells of orbiter, mercury, and gemini larvae are absent or strongly reduced. Therefore, these genes may encode components of the transduction apparatus.

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

    PubMed

    Herget, Meike; Scheibinger, Mirko; Guo, Zhaohua; Jan, Taha A; Adams, Christopher M; Cheng, Alan G; Heller, Stefan

    2013-01-01

    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.

  11. Regional analysis of whole cell currents from hair cells of the turtle posterior crista.

    PubMed

    Brichta, Alan M; Aubert, Anne; Eatock, Ruth Anne; Goldberg, Jay M

    2002-12-01

    The turtle posterior crista is made up of two hemicristae, each consisting of a central zone containing type I and type II hair cells and a surrounding peripheral zone containing only type II hair cells and extending from the planum semilunatum to the nonsensory torus. Afferents from various regions of a hemicrista differ in their discharge properties. To see if afferent diversity is related to the basolateral currents of the hair cells innervated, we selectively harvested type I and II hair cells from the central zone and type II hair cells from two parts of the peripheral zone, one near the planum and the other near the torus. Voltage-dependent currents were studied with the whole cell, ruptured-patch method and characterized in voltage-clamp mode. We found regional differences in both outwardly and inwardly rectifying voltage-sensitive currents. As in birds and mammals, type I hair cells have a distinctive outwardly rectifying current (I(K,L)), which begins activating at more hyperpolarized voltages than do the outward currents of type II hair cells. Activation of I(K,L) is slow and sigmoidal. Maximal outward conductances are large. Outward currents in type II cells vary in their activation kinetics. Cells with fast kinetics are associated with small conductances and with partial inactivation during 200-ms depolarizing voltage steps. Almost all type II cells in the peripheral zone and many in the central zone have fast kinetics. Some type II cells in the central zone have large outward currents with slow kinetics and little inactivation. Although these currents resemble I(K,L), they can be distinguished from the latter both electrophysiologically and pharmacologically. There are two varieties of inwardly rectifying currents in type II hair cells: activation of I(K1) is rapid and monoexponential, whereas that of I(h) is slow and sigmoidal. Many type II cells either have both inward currents or only have I(K1); very few cells only have I(h). Inward currents are

  12. Synchrotron nanoscopy imaging study of scalp hair in breast cancer patients and healthy individuals: Difference in medulla loss and cortical membrane enhancements.

    PubMed

    Han, Sung-Mi; Chikawa, Jun-Ichi; Jeon, Jae-Kun; Hwang, Min-Young; Lim, Jun; Jeong, Young-Ju; Park, Sung-Hwan; Kim, Hong-Tae; Jheon, Sanghoon; Kim, Jong-Ki

    2016-01-01

    Nanoscopic synchrotron X-ray imaging was performed on scalp hair samples of patients with breast cancer and healthy individuals to investigate any structural differences as diagnostic tool. Hair strands were divided into 2-3 segments along the strands from root to tip, followed by imaging either in projection or in CT scanning with a monochromatic 6.78-keV X-ray using zone-plate optics with a resolving power of 60 nm. All the examined cancer hairs exhibited medulla loss with cancer stage-dependent pattern; complete loss, discontinuous or trace along the strands. In contrast, medullas were well retained without complete loss in the healthy hair. In the CT-scanned axial images, the cortical spindle compartments had no contrast in the healthy hair, but appeared hypointense in contrast to the surrounding hyperintense cortical membrane complex in the cancer hair. In conclusion, observation of medulla loss and cortical membrane enhancements in the hair strands of breast cancer patients demonstrated structural variations in the cancer hair, providing a new platform for further synchrotron X-ray imaging study of screening breast cancer patients. © 2015 Wiley Periodicals, Inc.

  13. Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method.

    PubMed

    Ohnishi, Hiroe; Skerleva, Desislava; Kitajiri, Shin-ichiro; Sakamoto, Tatsunori; Yamamoto, Norio; Ito, Juichi; Nakagawa, Takayuki

    2015-07-10

    Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Across-frequency behavioral estimates of the contribution of inner and outer hair cell dysfunction to individualized audiometric loss

    PubMed Central

    Johannesen, Peter T.; Pérez-González, Patricia; Lopez-Poveda, Enrique A.

    2014-01-01

    Identifying the multiple contributors to the audiometric loss of a hearing impaired (HI) listener at a particular frequency is becoming gradually more useful as new treatments are developed. Here, we infer the contribution of inner (IHC) and outer hair cell (OHC) dysfunction to the total audiometric loss in a sample of 68 hearing aid candidates with mild-to-severe sensorineural hearing loss, and for test frequencies of 0.5, 1, 2, 4, and 6 kHz. It was assumed that the audiometric loss (HLTOTAL) at each test frequency was due to a combination of cochlear gain loss, or OHC dysfunction (HLOHC), and inefficient IHC processes (HLIHC), all of them in decibels. HLOHC and HLIHC were estimated from cochlear I/O curves inferred psychoacoustically using the temporal masking curve (TMC) method. 325 I/O curves were measured and 59% of them showed a compression threshold (CT). The analysis of these I/O curves suggests that (1) HLOHC and HLIHC account on average for 60–70 and 30–40% of HLTOTAL, respectively; (2) these percentages are roughly constant across frequencies; (3) across-listener variability is large; (4) residual cochlear gain is negatively correlated with hearing loss while residual compression is not correlated with hearing loss. Altogether, the present results support the conclusions from earlier studies and extend them to a wider range of test frequencies and hearing-loss ranges. Twenty-four percent of I/O curves were linear and suggested total cochlear gain loss. The number of linear I/O curves increased gradually with increasing frequency. The remaining 17% I/O curves suggested audiometric losses due mostly to IHC dysfunction and were more frequent at low (≤1 kHz) than at high frequencies. It is argued that in a majority of listeners, hearing loss is due to a common mechanism that concomitantly alters IHC and OHC function and that IHC processes may be more labile in the apex than in the base. PMID:25100940

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

    NASA Technical Reports Server (NTRS)

    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 < 0.5 to 1.25 microns and were largest in Type B and smallest in Type F and Type E cells. Sensitivity, defined as the slope of the normalized displacement-response curve, was inversely correlated with linear range. 4. The contribution of geometric factors associated with the hair bundle to linear range and sensitivity were predicted from realistic models of utricular hair bundles created using morphological data obtained from light and electron microscopy. Three factors, including 1) the inverse ratio of the lengths of the kinocilium and longest stereocilia, representing the

  16. Hair camouflage: A comprehensive review.

    PubMed

    Saed, Stephanie; Ibrahim, Omer; Bergfeld, Wilma F

    2016-12-01

    Hair is venerated, cherished, and desired in societies throughout the world. Both women and men express their individual identities through their hairstyles. Healthy hair contributes to successful social assimilation, employment, and overall quality of life. Therefore, hair loss can have detrimental effects on almost every aspect of a person's life. In this review, we discuss the myriad of options that aid in concealing and camouflaging hair loss to facilitate a healthier-appearing scalp. Camouflage options for patients who suffer from hair loss include full or partial wigs, hair extensions, concealing powders and sprays, surgical tattoos, and hair transplants. We describe these modalities in detail and discuss their respective advantages and disadvantages.

  17. Hair camouflage: A comprehensive review.

    PubMed

    Saed, Stephanie; Ibrahim, Omer; Bergfeld, Wilma F

    2017-03-01

    Hair is venerated, cherished, and desired in societies throughout the world. Both women and men express their individual identities through their hairstyles. Healthy hair contributes to successful social assimilation, employment, and overall quality of life. Therefore, hair loss can have detrimental effects on almost every aspect of a person's life. In this review, we discuss the myriad of options that aid in concealing and camouflaging hair loss to facilitate a healthier-appearing scalp. Camouflage options for patients who suffer from hair loss include full or partial wigs, hair extensions, concealing powders and sprays, surgical tattoos, and hair transplants. We describe these modalities in detail and discuss their respective advantages and disadvantages.

  18. Generation of inner ear organoids containing functional hair cells from human pluripotent stem cells.

    PubMed

    Koehler, Karl R; Nie, Jing; Longworth-Mills, Emma; Liu, Xiao-Ping; Lee, Jiyoon; Holt, Jeffrey R; Hashino, Eri

    2017-06-01

    The derivation of human inner ear tissue from pluripotent stem cells would enable in vitro screening of drug candidates for the treatment of hearing and balance dysfunction and may provide a source of cells for cell-based therapies of the inner ear. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and WNT signaling to generate multiple otic-vesicle-like structures from a single stem-cell aggregate. Over 2 months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR-Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system should facilitate the study of human inner ear development and research on therapies for diseases of the inner ear.

  19. Heat pulse excitability of vestibular hair cells and afferent neurons

    PubMed Central

    Brichta, Alan M.; Tabatabaee, Hessam; Boutros, Peter J.; Ahn, JoongHo; Della Santina, Charles C.; Poppi, Lauren A.; Lim, Rebecca

    2016-01-01

    In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT. An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at −68 mV and in 67% of hair cells at −60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability. PMID:27226448

  20. Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt)

    PubMed Central

    Erickson, Timothy; Morgan, Clive P; Olt, Jennifer; Hardy, Katherine; Busch-Nentwich, Elisabeth; Maeda, Reo; Clemens, Rachel; Krey, Jocelyn F; Nechiporuk, Alex; Barr-Gillespie, Peter G; Marcotti, Walter; Nicolson, Teresa

    2017-01-01

    Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non-syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP-tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle. DOI: http://dx.doi.org/10.7554/eLife.28474.001 PMID:28534737

  1. AN ADENYLYL CYCLASE SIGNALING PATHWAY PREDICTS DIRECT DOPAMINERGIC INPUT TO VESTIBULAR HAIR CELLS

    PubMed Central

    DRESCHER, M. J.; CHO, W. J.; FOLBE, A. J.; SELVAKUMAR, D.; KEWSON, D. T.; ABU-HAMDAN, M. D.; OH, C. K.; RAMAKRISHNAN, N. A.; HATFIELD, J. S.; KHAN, K. M.; ANNE, S.; HARPOOL, E. C.; DRESCHER, D. G.

    2010-01-01

    Adenylyl cyclase signaling pathways have been identified in a model hair cell preparation from the trout saccule, for which the hair cell is the only intact cell type. The use of degenerate primers targeting cDNA sequence conserved across adenylyl cyclase (AC) isoforms, and RT-PCR, coupled with cloning of amplification products, indicated expression of AC9, AC7 and AC5/6, with cloning efficiencies of 11:5:2. AC9 and AC5/6 are inhibited by Ca2+, the former in conjunction with calcineurin, and message for calcineurin has also been identified in the trout saccular hair cell layer. AC7 is independent of Ca2+. Given the lack of detection of calcium/calmodulin-activated isoforms previously suggested to mediate adenylyl cyclase activation in the absence of Gαs in mammalian cochlear hair cells, the issue of hair-cell Gαs mRNA expression was re-examined in the teleost vestibular hair cell model. Two full-length coding sequences were obtained for Gαs/olf in the vestibular type II-like hair cells of the trout saccule. Two messages for Gαi have also been detected in the hair cell layer, one with homology to Gαi1 and the second with homology to Gαi3 of higher vertebrates. Both Gαs/olf protein and Gαi1/Gαi3 protein were immunolocalized to stereocilia and to the base of the hair cell, the latter consistent with sites of efferent input. While a signaling event coupling to Gαs/olf and Gαi1/Gαi3 in the stereocilia is currently unknown, signaling with Gαs/olf, Gαi3, and AC5/6 at the base of the hair cell would be consistent with transduction pathways activated by dopaminergic efferent input. mRNA for dopamine receptors D1A4 and five forms of dopamine D2 were found to be expressed in the teleost saccular hair cell layer, representing information on vestibular hair cell expression not directly available for higher vertebrates. Dopamine D1A receptor would couple to Gαolf and activation of AC5/6. Co-expression with dopamine D2 receptor, which itself couples to Gαi3 and AC

  2. Neomycin damage and regeneration of hair cells in both mechanoreceptor and electroreceptor lateral line organs of the larval Siberian sturgeon (Acipenser baerii).

    PubMed

    Fan, Chunxin; Zou, Sha; Wang, Jian; Zhang, Bo; Song, Jiakun

    2016-05-01

    The lateral line found in some amphibians and fishes has two distinctive classes of sensory organs: mechanoreceptors (neuromasts) and electroreceptors (ampullary organs). Hair cells in neuromasts can be damaged by aminoglycoside antibiotics and they will regenerate rapidly afterward. Aminoglycoside sensitivity and the capacity for regeneration have not been investigated in ampullary organs. We treated Siberian sturgeon (Acipenser baerii) larvae with neomycin and observed loss and regeneration of sensory hair cells in both organs by labeling with DASPEI and scanning electron microscopy (SEM). The numbers of sensory hair cells in both organs were reduced to the lowest levels at 6 hours posttreatment (hpt). New sensory hair cells began to appear at 12 hpt and were regenerated completely in 7 days. To reveal the possible mechanism for ampullary hair cell regeneration, we analyzed cell proliferation and the expression of neural placodal gene eya1 during regeneration. Both cell proliferation and eya1 expression were concentrated in peripheral mantle cells and both increased to the highest level at 12 hpt, which is consistent with the time course for regeneration of the ampullary hair cells. Furthermore, we used Texas Red-conjugated gentamicin in an uptake assay following pretreatment with a cation channel blocker (amiloride) and found that entry of the antibiotic was suppressed in both organs. Together, our results indicate that ampullary hair cells in Siberian sturgeon larvae can be damaged by neomycin exposure and they can regenerate rapidly. We suggest that the mechanisms for aminoglycoside uptake and hair cell regeneration are conserved for mechanoreceptors and electroreceptors. J. Comp. Neurol. 524:1443-1456, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  3. Magnetic Nanoparticles as Mechanical Actuators of Inner Ear Hair Cells

    DTIC Science & Technology

    2016-01-13

    AFRL-AFOSR-VA-TR-2016-0039 Magnetic nanoparticles as mechanical actuators of inner ear hair cells Dolores Bozovic UNIVERSITY OF CALIFORNIA LOS...4. TITLE AND SUBTITLE Magnetic nanoparticles as mechanical actuators of inner ear hair cells 5a. CONTRACT NUMBER N.A. 5b. GRANT NUMBER FA9550-12...13. SUPPLEMENTARY NOTES 14. ABSTRACT The collaborative project was designed to edevelop the use of magnetic nanoparticles to manipulate auditory hair

  4. Genetic and pharmacological intervention for treatment/prevention of hearing loss

    PubMed Central

    Cotanche, Douglas A.

    2008-01-01

    Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans. Learning outcomes The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea. PMID:18455177

  5. Genetic and pharmacological intervention for treatment/prevention of hearing loss.

    PubMed

    Cotanche, Douglas A

    2008-01-01

    Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans. The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea.

  6. Investigation of Notch Signaling during Spontaneous Regeneration of Cochlear Hair Cells

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0475 TITLE: Investigation of Notch Signaling during Spontaneous Regeneration of Cochlear Hair Cells PRINCIPAL...Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Investigation of Notch Signaling during Spontaneous Regeneration of Cochlear Hair Cells 5b...inherent to military settings. These noise exposures damage and kill sensory hair cells (HCs) found in the cochlea of the inner ear, resulting in permanent

  7. Hair transplantation.

    PubMed

    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.

  8. d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

    PubMed Central

    Kirkwood, Nerissa K.; O'Reilly, Molly; Derudas, Marco; Kenyon, Emma J.; Huckvale, Rosemary; van Netten, Sietse M.; Ward, Simon E.; Richardson, Guy P.; Kros, Corné J.

    2017-01-01

    Aminoglycoside antibiotics are widely used for the treatment of life-threatening bacterial infections, but cause permanent hearing loss in a substantial proportion of treated patients. The sensory hair cells of the inner ear are damaged following entry of these antibiotics via the mechano-electrical transducer (MET) channels located at the tips of the hair cell's stereocilia. d-Tubocurarine (dTC) is a MET channel blocker that reduces the loading of gentamicin-Texas Red (GTTR) into rat cochlear hair cells and protects them from gentamicin treatment. Berbamine is a structurally related alkaloid that reduces GTTR labeling of zebrafish lateral-line hair cells and protects them from aminoglycoside-induced cell death. Both compounds are thought to reduce aminoglycoside entry into hair cells through the MET channels. Here we show that dTC (≥6.25 μM) or berbamine (≥1.55 μM) protect zebrafish hair cells in vivo from neomycin (6.25 μM, 1 h). Protection of zebrafish hair cells against gentamicin (10 μM, 6 h) was provided by ≥25 μM dTC or ≥12.5 μM berbamine. Hair cells in mouse cochlear cultures are protected from longer-term exposure to gentamicin (5 μM, 48 h) by 20 μM berbamine or 25 μM dTC. Berbamine is, however, highly toxic to mouse cochlear hair cells at higher concentrations (≥30 μM) whilst dTC is not. The absence of toxicity in the zebrafish assays prompts caution in extrapolating results from zebrafish neuromasts to mammalian cochlear hair cells. MET current recordings from mouse outer hair cells (OHCs) show that both compounds are permeant open-channel blockers, rapidly and reversibly blocking the MET channel with half-blocking concentrations of 2.2 μM (dTC) and 2.8 μM (berbamine) in the presence of 1.3 mM Ca2+ at −104 mV. Berbamine, but not dTC, also blocks the hair cell's basolateral K+ current, IK,neo, and modeling studies indicate that berbamine permeates the MET channel more readily than dTC. These studies reveal key properties of MET

  9. An adenylyl cyclase signaling pathway predicts direct dopaminergic input to vestibular hair cells.

    PubMed

    Drescher, M J; Cho, W J; Folbe, A J; Selvakumar, D; Kewson, D T; Abu-Hamdan, M D; Oh, C K; Ramakrishnan, N A; Hatfield, J S; Khan, K M; Anne, S; Harpool, E C; Drescher, D G

    2010-12-29

    Adenylyl cyclase (AC) signaling pathways have been identified in a model hair cell preparation from the trout saccule, for which the hair cell is the only intact cell type. The use of degenerate primers targeting cDNA sequence conserved across AC isoforms, and reverse transcription-polymerase chain reaction (RT-PCR), coupled with cloning of amplification products, indicated expression of AC9, AC7 and AC5/6, with cloning efficiencies of 11:5:2. AC9 and AC5/6 are inhibited by Ca(2+), the former in conjunction with calcineurin, and message for calcineurin has also been identified in the trout saccular hair cell layer. AC7 is independent of Ca(2+). Given the lack of detection of calcium/calmodulin-activated isoforms previously suggested to mediate AC activation in the absence of Gαs in mammalian cochlear hair cells, the issue of hair-cell Gαs mRNA expression was re-examined in the teleost vestibular hair cell model. Two full-length coding sequences were obtained for Gαs/olf in the vestibular type II-like hair cells of the trout saccule. Two messages for Gαi have also been detected in the hair cell layer, one with homology to Gαi1 and the second with homology to Gαi3 of higher vertebrates. Both Gαs/olf protein and Gαi1/Gαi3 protein were immunolocalized to stereocilia and to the base of the hair cell, the latter consistent with sites of efferent input. Although a signaling event coupling to Gαs/olf and Gαi1/Gαi3 in the stereocilia is currently unknown, signaling with Gαs/olf, Gαi3, and AC5/6 at the base of the hair cell would be consistent with transduction pathways activated by dopaminergic efferent input. mRNA for dopamine receptors D1A4 and five forms of dopamine D2 were found to be expressed in the teleost saccular hair cell layer, representing information on vestibular hair cell expression not directly available for higher vertebrates. Dopamine D1A receptor would couple to Gαolf and activation of AC5/6. Co-expression with dopamine D2 receptor, which

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

    PubMed Central

    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

  11. Hair and Physiological Baldness

    PubMed Central

    Mercantini, Edward S.

    1965-01-01

    Human hair is one of the structures of the body about which little is generally known. Disease affecting the hair is often minimized or ignored by physicians because of lack of knowledge of this rudimentary organ. However, the patient's attitude toward hair loss is very different from the doctor's and he feels great concern about such loss. The development, growth and morphology of human hair are briefly presented. Experimental work which will increase our knowledge of hair growth and loss is reviewed. The various forms of physiological alopecia from birth onward are discussed, with special emphasis on the least-known type of physiological baldness, “male-pattern baldness” in the adult female. PMID:14312445

  12. Analysis of the Proteome of Hair-Cell Stereocilia by Mass Spectrometry

    PubMed Central

    Krey, Jocelyn F.; Wilmarth, Philip A.; David, Larry L.; Barr-Gillespie, Peter G.

    2017-01-01

    Characterization of proteins that mediate mechanotransduction by hair cells, the sensory cells of the inner ear, is hampered by the scarcity of these cells and their sensory organelle, the hair bundle. Mass spectrometry, with its high sensitivity and identification precision, is the ideal method for determining which proteins are present in bundles and what proteins they interact with. We describe here the isolation of mouse hair bundles, as well as preparation of bundle-protein samples for mass spectrometry. We also describe protocols for data-dependent (shotgun) and parallel-reaction-monitoring (targeted) mass spectrometry that allow us to identify and quantify proteins of the hair bundle. These sensitive methods are particularly useful for comparing proteomes of wild-type and mice with deafness mutations affecting hair-bundle proteins. (120 words; maximum 250) PMID:28109437

  13. NonScarring Diffuse Hair Loss in Women: a Clinico-Etiological Study from tertiary care center in North-West India.

    PubMed

    Poonia, Kavita; Thami, Gurvinder Pal; Bhalla, Mala; Jaiswal, Shivani; Sandhu, Jasleen

    2018-05-17

    Diffuse hair loss (DHL) is a common problem in adult women and has a major impact on quality of life. Ascertaining the etiological diagnosis is a challenging task in such patients. Satisfactory treatment can only be instituted after ascertaining the cause of hair loss. To study the clinico-epidemiological profile of nonscarring DHL in females and to ascertain its underlying etiological factors. Of a total of 110 females, who presented with nonscarring DHL to the outpatient dermatology department, 100 qualified for inclusion in the study. A detailed history, clinical examination, and laboratory investigations were performed in all the patients. Statistical analysis was performed on the data collected. Of 100 cases of DHL which were included in the study, commonest was chronic telogen effluvium (CTE) (62%), followed by female pattern hair loss (FPHL) (22%) and acute telogen effluvium (ATE) (16%). Incidence of hair loss was highest in 21-40 years age group. Psychological stress was seen to be a precipitating factor in 18 patients and found most commonly in women belong to CTE group (n-16, 25.8%). Hemoglobin levels ranged from 80 to 142 gm/L (mean: 119 ± 110). Low hemoglobin level (<120 gm/L) was observed in 57% patients. Total serum ferritin <10 ng/mL was seen in 20 patients, vitamin B12 < 211 pg/mL in 76 cases, vitamin D3 < 30 ng/mL in 81 cases. Subclinical hypothyroidism was present in 11% cases. Nonscarring DHL is a multifactorial condition with highest incidence in 21- to 40-year age group. Serum ferritin, serum vitamin B12, and D3 levels seem to have a contributing role in the pathogenesis of hair loss, and their supplementation may be needed for a faster regrowth of hair in all cases of hair loss irrespective of the pattern. © 2018 Wiley Periodicals, Inc.

  14. Root Hairs

    PubMed Central

    Grierson, Claire; Nielsen, Erik; Ketelaarc, Tijs; Schiefelbein, John

    2014-01-01

    Roots hairs are cylindrical extensions of root epidermal cells that are important for acquisition of nutrients, microbe interactions, and plant anchorage. The molecular mechanisms involved in the specification, differentiation, and physiology of root hairs in Arabidopsis are reviewed here. Root hair specification in Arabidopsis is determined by position-dependent signaling and molecular feedback loops causing differential accumulation of a WD-bHLH-Myb transcriptional complex. The initiation of root hairs is dependent on the RHD6 bHLH gene family and auxin to define the site of outgrowth. Root hair elongation relies on polarized cell expansion at the growing tip, which involves multiple integrated processes including cell secretion, endomembrane trafficking, cytoskeletal organization, and cell wall modifications. The study of root hair biology in Arabidopsis has provided a model cell type for insights into many aspects of plant development and cell biology. PMID:24982600

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

    NASA Technical Reports Server (NTRS)

    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.

  16. Genetically induced cell death in bulge stem cells reveals their redundancy for hair and epidermal regeneration.

    PubMed

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

    2015-03-01

    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 Setd8 eliminated the contribution of bulge cells to hair follicle regeneration through inhibition of cell division and induction of cell death, but the growth and morphology of hair follicles were unaffected. Furthermore, ablation of Setd8 in the hair follicle bulge blocked the contribution of K19-postive stem cells to wounded epidermis, but the wound healing process was unaltered. Our data indicate that quiescent bulge stem cells are dispensable for hair follicle regeneration and epidermal injury in the short term and support the hypothesis that quiescent and cycling stem cell populations are equipotent. © 2014 AlphaMed Press.

  17. Hair growth-promoting effect of Carthamus tinctorius floret extract.

    PubMed

    Junlatat, Jintana; Sripanidkulchai, Bungorn

    2014-07-01

    The florets of Carthamus tinctorius L. have traditionally been used for hair growth promotion. This study aimed to examine the potential of hydroxysafflor yellow A-rich C. tinctorius extract (CTE) on hair growth both in vitro and in vivo. The effect of CTE on cell proliferation and hair growth-associated gene expression in dermal papilla cells and keratinocytes (HaCaT) was determined. In addition, hair follicles from mouse neonates were isolated and cultured in media supplemented with CTE. Moreover, CTE was applied topically on the hair-shaved skin of female C57BL/6 mice, and the histological profile of the skin was investigated. C. tinctorius floret ethanolic extract promoted the proliferation of both dermal papilla cells and HaCaT and significantly stimulated hair growth-promoting genes, including vascular endothelial growth factor and keratinocyte growth factor. In contrast, CTE suppressed the expression of transforming growth factor-β1 that is the hair loss-related gene. Furthermore, CTE treatment resulted in a significant increase in the length of cultured hair follicles and stimulated the growth of hair with local effects in mice. The results provided the preclinical data to support the potential use of CTE as a hair growth-promoting agent. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Noise-induced inner hair cell ribbon loss disturbs central arc mobilization: a novel molecular paradigm for understanding tinnitus.

    PubMed

    Singer, Wibke; Zuccotti, Annalisa; Jaumann, Mirko; Lee, Sze Chim; Panford-Walsh, Rama; Xiong, Hao; Zimmermann, Ulrike; Franz, Christoph; Geisler, Hyun-Soon; Köpschall, Iris; Rohbock, Karin; Varakina, Ksenya; Verpoorten, Sandrine; Reinbothe, Thomas; Schimmang, Thomas; Rüttiger, Lukas; Knipper, Marlies

    2013-02-01

    Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury.

  19. Hair Shaft Damage from Heat and Drying Time of Hair Dryer

    PubMed Central

    Lee, Yoonhee; Kim, Youn-Duk; Hyun, Hye-Jin; Pi, Long-quan; Jin, Xinghai

    2011-01-01

    Background Hair dryers are commonly used and can cause hair damage such as roughness, dryness and loss of hair color. It is important to understand the best way to dry hair without causing damage. Objective The study assessed changes in the ultra-structure, morphology, moisture content, and color of hair after repeated shampooing and drying with a hair dryer at a range of temperatures. Methods A standardized drying time was used to completely dry each hair tress, and each tress was treated a total of 30 times. Air flow was set on the hair dryer. The tresses were divided into the following five test groups: (a) no treatment, (b) drying without using a hair dryer (room temperature, 20℃), (c) drying with a hair dryer for 60 seconds at a distance of 15 cm (47℃), (d) drying with a hair dryer for 30 seconds at a distance of 10 cm (61℃), (e) drying with a hair dryer for 15 seconds at a distance of 5 cm (95℃). Scanning and transmission electron microscopy (TEM) and lipid TEM were performed. Water content was analyzed by a halogen moisture analyzer and hair color was measured with a spectrophotometer. Results Hair surfaces tended to become more damaged as the temperature increased. No cortex damage was ever noted, suggesting that the surface of hair might play a role as a barrier to prevent cortex damage. Cell membrane complex was damaged only in the naturally dried group without hair dryer. Moisture content decreased in all treated groups compared to the untreated control group. However, the differences in moisture content among the groups were not statistically significant. Drying under the ambient and 95℃ conditions appeared to change hair color, especially into lightness, after just 10 treatments. Conclusion Although using a hair dryer causes more surface damage than natural drying, using a hair dryer at a distance of 15 cm with continuous motion causes less damage than drying hair naturally. PMID:22148012

  20. A nonlinear cochlear model with the outer hair cell piezoelectric activity

    NASA Astrophysics Data System (ADS)

    Jiang, Xiaoai; Grosh, Karl

    2003-10-01

    In this paper we present a simple cochlear model which captures the most important aspect of nonlinearity in the cochlea-the nonlinearity caused by the piezoelectric-like activity of outer hair cells and the variable conductance of the outer hair cell stereocilia. A one-dimensional long-wave model is built to simulate the dynamic response of the fluid-loaded basilar membrane. The basilar membrane is simulated as isolated linear oscillators along the cochlear length, and its motion is coupled with the fluid pressure and the nonlinear force produced by the outer hair cells. As the basilar membrane moves, the fluid shears stereocilia, and the resulting ion flow changes the transmembrane potential of the outer hair cells and subsequently their length, leading to further movement of the basilar membrane. The piezoelectric-like activity of the outer hair cell is simulated by a current source, and stereocilia motion is modeled as a varying conductance that changes as the basilar membrane moves. A solution in the time domain will be presented. [Work supported by NIH.

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

    PubMed

    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.

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

    PubMed Central

    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 (< 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

  3. Identification of hair shaft progenitors that create a niche for hair pigmentation

    PubMed Central

    Liao, Chung-Ping; Booker, Reid C.; Morrison, Sean J.; Le, Lu Q.

    2017-01-01

    Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20+ cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. PMID:28465357

  4. BONE MARROW MESENCHYMAL STEM CELLS ARE PROGENITORS IN VITRO FOR INNER EAR HAIR CELLS

    PubMed Central

    Jeon, Sang-Jun; Oshima, Kazuo; Heller, Stefan; Edge, Albert S.B.

    2011-01-01

    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 differentiation to inner ear sensory cells. Some of the cells displayed F-actin positive protrusions in the morphology characteristic of hair cell stereociliary bundles. Hair cell markers were also induced by culture of mouse MSC-derived cells in contact with embryonic chick inner ear cells, and this induction was not due to a cell fusion event, because the chick hair cells could be identified with a chick-specific antibody and chick and mouse antigens were never found in the same cell. PMID:17113786

  5. Large basolateral processes on type II hair cells are novel processing units in mammalian vestibular organs.

    PubMed

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

    2014-10-01

    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 that extend laterally from the hair cell base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells vary in shape, size, and branching, with the longest processes extending three to four hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Furthermore, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network among type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3-6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells and suggest that type II hair cells may directly communicate with each other, which has not been described in vertebrates. © 2014 Wiley Periodicals, Inc.

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

    NASA Technical Reports Server (NTRS)

    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

  7. A pilot split-scalp study of combined fractional radiofrequency microneedling and 5% topical minoxidil in treating male pattern hair loss.

    PubMed

    Yu, A-J; Luo, Y-J; Xu, X-G; Bao, L-L; Tian, T; Li, Z-X; Dong, Y-X; Li, Y-H

    2018-06-27

    Various trials have been conducted on the management of male pattern hair loss (MPHL), but the outcomes often seem to be limited. Adjuvant therapies are urgently needed. To evaluate the efficacy and safety of combined fractional radiofrequency microneedling (FRM) and 5% topical minoxidil in the treatment of male pattern hair loss. In total, 19 Chinese men were enrolled in this randomized, controlled, split-scalp trial. Participants received monotherapy with 5% topical minoxidil twice daily to one half of the scalp, while on the other half of the scalp the treatment with twice-daily 5% topical minoxidil was combined with five sessions of FRM at 4-week intervals. Mean hair count and hair thickness, global assessment by the investigators, subject self-assessment and adverse effects were assessed. After 5 months of treatment, mean hair count increased from 44.12 ± 21.58 to 73.14 ± 25.45 on the combined-therapy side and from 46.22 ± 18.77 to 63.21 ± 19.22 on the monotherapy side, while mean hair thickness increased from 53 ± 13 μm to 71 ± 15 μm and from 52 ± 16 μm to 66 ± 14 μm, respectively. Compared with the monotherapy side, the combined-therapy side had a higher degree of improvement in both hair count (P = 0.01) and hair thickness (P = 0.02). Combined treatment with fractional radiofrequency microneedle and 5% topical minoxidil could be an effective and safe treatment option for male pattern hair loss. © 2018 British Association of Dermatologists.

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

    NASA Technical Reports Server (NTRS)

    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.

  9. Generation of iPS-derived model cells for analyses of hair shaft differentiation.

    PubMed

    Kido, Takumi; Horigome, Tomoatsu; Uda, Minori; Adachi, Naoki; Hirai, Yohei

    2017-09-01

    Biological evaluation of hair growth/differentiation activity in vitro has been a formidable challenge, primarily due to the lack of relevant model cell systems. To solve this problem, we generated a stable model cell line in which successive differentiation via epidermal progenitors to hair components is easily inducible and traceable. Mouse induced pluripotent stem (iPS) cell-derived cells were selected to stably express a tetracycline (Tet)-inducible bone morphogenic protein-4 (BMP4) expression cassette and a luciferase reporter driven by a hair-specific keratin 31 gene (krt31) promoter (Tet-BMP4-KRT31-Luc iPS). While Tet- BMP4-KRT31-Luc iPS cells could be maintained as stable iPS cells, the cells differentiated to produce luciferase luminescence in the presence of all-trans retinoic acid (RA) and doxycycline (Dox), and addition of a hair differentiation factor significantly increased luciferase fluorescence. Thus, this cell line may provide a reliable cell-based screening system to evaluate drug candidates for hair differentiation activity.

  10. The biology of hair diversity.

    PubMed

    Westgate, Gillian E; Botchkareva, Natalia V; Tobin, Desmond J

    2013-08-01

    Hair diversity, its style, colour, shape and growth pattern is one of our most defining characteristics. The natural versus temporary style is influenced by what happens to our hair during our lifetime, such as genetic hair loss, sudden hair shedding, greying and pathological hair loss in the various forms of alopecia because of genetics, illness or medication. Despite the size and global value of the hair care market, our knowledge of what controls the innate and within-lifetime characteristics of hair diversity remains poorly understood. In the last decade, drivers of knowledge have moved into the arena of genetics where hair traits are obvious and measurable and genetic polymorphisms are being found that raise valuable questions about the biology of hair growth. The recent discovery that the gene for trichohyalin contributes to hair shape comes as no surprise to the hair biologists who have believed for 100 years that hair shape is linked to the structure and function of the inner root sheath. Further conundrums awaiting elucidation include the polymorphisms in the androgen receptor (AR) described in male pattern alopecia whose location on the X chromosome places this genetic contributor into the female line. The genetics of female hair loss is less clear with polymorphisms in the AR not associated with female pattern hair loss. Lifestyle choices are also implicated in hair diversity. Greying, which also has a strong genetic component, is often suggested to have a lifestyle (stress) influence and hair follicle melanocytes show declining antioxidant protection with age and lowered resistance to stress. It is likely that hair research will undergo a renaissance on the back of the rising information from genetic studies as well as the latest contributions from the field of epigenetics. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  11. Interrelated striated elements in vestibular hair cells of the rat

    NASA Technical Reports Server (NTRS)

    Ross, M. D.; Bourne, C.

    1983-01-01

    A series of interrelated striated organelles in types I and II vestibular hair cells of the rat which appear to be less developed in cochlear hair cells have been revealed by unusual fixation procedures, suggesting that contractile elements may play a role in sensory transduction in the inner ear, especially in the vestibular system. Included in the series of interrelated striated elements are the cuticular plate and its basal attachments to the hair cell margins, the connections of the strut array of the kinociliary basal body to the cuticular plate, and striated organelles associated with the plasma membrane and extending below the apical junctional complexes.

  12. Identification of hair shaft progenitors that create a niche for hair pigmentation.

    PubMed

    Liao, Chung-Ping; Booker, Reid C; Morrison, Sean J; Le, Lu Q

    2017-04-15

    Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20 + cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes. © 2017 Liao et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Hair cell regeneration in the chick inner ear following acoustic trauma: ultrastructural and immunohistochemical studies.

    PubMed

    Umemoto, M; Sakagami, M; Fukazawa, K; Ashida, K; Kubo, T; Senda, T; Yoneda, Y

    1995-09-01

    The regeneration of hair cells in the chick inner ear following acoustic trauma was examined using transmission electron microscopy. In addition, the localization of proliferation cell nuclear antigen (PCNA) and basic fibroblast growth factor (b-FGF) was demonstrated immunohistochemically. The auditory sensory epithelium of the normal chick consists of short and tall hair cells and supporting cells. Immediately after noise exposure to a 1500-Hz pure tone at a sound pressure level of 120 decibels for 48 h, all the short hair cells disappeared in the middle region of the auditory epithelium. Twelve hours to 1 day after exposure, mitotic cells, binucleate cells and PCNA-positive supporting cells were observed, and b-FGF immunoreactivity was shown in the supporting cells and glial cells near the habenula perforata. Spindle-shaped hair cells with immature stereocilia and a kinocilium appeared 3 days after exposure; these cells had synaptic connections with the newly developed nerve endings. The spindle-shaped hair cell is considered to be a transitional cell in the lineage of the supporting cell to the mature short hair cell. These results indicate that, after acoustic trauma, the supporting cells divide and differentiate into new short hair cells via spindle-shaped hair cells. Furthermore, it is suggested that b-FGF is related to the proliferation of the supporting cells and the extension of the nerve fibers.

  14. The Impact of 5α-Reductase Inhibitor Use for Male Pattern Hair Loss on Men's Health.

    PubMed

    Said, Mohammed A; Mehta, Akanksha

    2018-06-16

    Male pattern hair loss, mediated by dihydrotestosterone, is a common hair loss disorder, affecting over 50% of men over the age of 50. The 5-α reductase inhibitors, finasteride and dutasteride, are Food and Drug Administration-approved drugs for the treatment of this disorder. Several recent studies have reported adverse sexual and spermatogenic events among young men using 5-α reductase inhibitors, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility. In this review, we summarize and analyze the literature regarding the efficacy and safety of these medications, with an overall focus on men's health. Finasteride for the treatment of male pattern hair loss was considered safe according to many previous clinical trials. However, these trials have been recently criticized for inadequate safety reporting. Comprehensive review of the current literature reveals that there is a disproportionately high number of men with 5-α reductase inhibitor-associated sexual dysfunction and infertility. Although uncommon, the use of 5-α reductase inhibitors is associated with serious and persistent sexual and reproductive side effects, such as erectile dysfunction, decreased ejaculate volume, decreased libido, and infertility.

  15. Proanthocyanidins from grape seeds promote proliferation of mouse hair follicle cells in vitro and convert hair cycle in vivo.

    PubMed

    Takahashi, T; Kamiya, T; Yokoo, Y

    1998-11-01

    For the purpose of discovering natural products which possess hair growing activity, we examined about 1000 kinds of plant extracts concerning growth-promoting activity with respect to hair follicle cells. After an extensive search, we discovered that proanthocyanidins extracted from grape seeds promote proliferation of hair follicle cells isolated from mice by about 230% relative to controls (100%); and that proanthocyanidins possess remarkable hair-cycle-converting activity from the telogen phase to the anagen phase in C3H mice in vivo test systems. The profile of the active fraction of the proanthocyanidins was elucidated by thiolytic degradation and tannase hydrolysis. We found that the constitutive monomers were epicatechin and catechin; and that the degree of polymerization was 3.5. We demonstrated the possibility of using the proanthocyanidins extracted from grape seeds as agents inducing hair growth.

  16. Epigenetic regulation of Atoh1 guides hair cell development in the mammalian cochlea.

    PubMed

    Stojanova, Zlatka P; Kwan, Tao; Segil, Neil

    2015-10-15

    In the developing cochlea, sensory hair cell differentiation depends on the regulated expression of the bHLH transcription factor Atoh1. In mammals, if hair cells die they do not regenerate, leading to permanent deafness. By contrast, in non-mammalian vertebrates robust regeneration occurs through upregulation of Atoh1 in the surviving supporting cells that surround hair cells, leading to functional recovery. Investigation of crucial transcriptional events in the developing organ of Corti, including those involving Atoh1, has been hampered by limited accessibility to purified populations of the small number of cells present in the inner ear. We used µChIP and qPCR assays of FACS-purified cells to track changes in the epigenetic status of the Atoh1 locus during sensory epithelia development in the mouse. Dynamic changes in the histone modifications H3K4me3/H3K27me3, H3K9ac and H3K9me3 reveal a progression from poised, to active, to repressive marks, correlating with the onset of Atoh1 expression and its subsequent silencing during the perinatal (P1 to P6) period. Inhibition of acetylation blocked the increase in Atoh1 mRNA in nascent hair cells, as well as ongoing hair cell differentiation during embryonic organ of Corti development ex vivo. These results reveal an epigenetic mechanism of Atoh1 regulation underlying hair cell differentiation and subsequent maturation. Interestingly, the H3K4me3/H3K27me3 bivalent chromatin structure observed in progenitors persists at the Atoh1 locus in perinatal supporting cells, suggesting an explanation for the latent capacity of these cells to transdifferentiate into hair cells, and highlighting their potential as therapeutic targets in hair cell regeneration. © 2015. Published by The Company of Biologists Ltd.

  17. Counter-rotational cell flows drive morphological and cell fate asymmetries in mammalian hair follicles.

    PubMed

    Cetera, Maureen; Leybova, Liliya; Joyce, Bradley; Devenport, Danelle

    2018-05-01

    Organ morphogenesis is a complex process coordinated by cell specification, epithelial-mesenchymal interactions and tissue polarity. A striking example is the pattern of regularly spaced, globally aligned mammalian hair follicles, which emerges through epidermal-dermal signaling and planar polarized morphogenesis. Here, using live-imaging, we discover that developing hair follicles polarize through dramatic cell rearrangements organized in a counter-rotational pattern of cell flows. Upon hair placode induction, Shh signaling specifies a radial pattern of progenitor fates that, together with planar cell polarity, induce counter-rotational rearrangements through myosin and ROCK-dependent polarized neighbour exchanges. Importantly, these cell rearrangements also establish cell fate asymmetry by repositioning radial progenitors along the anterior-posterior axis. These movements concurrently displace associated mesenchymal cells, which then signal asymmetrically to maintain polarized cell fates. Our results demonstrate how spatial patterning and tissue polarity generate an unexpected collective cell behaviour that in turn, establishes both morphological and cell fate asymmetry.

  18. A ‘calcium capacitor’ shapes cholinergic inhibition of cochlear hair cells

    PubMed Central

    Fuchs, Paul Albert

    2014-01-01

    Efferent cholinergic neurons project from the brainstem to inhibit sensory hair cells of the vertebrate inner ear. This inhibitory synapse combines the activity of an unusual class of ionotropic cholinergic receptor with that of nearby calcium-dependent potassium channels to shunt and hyperpolarize the hair cell. Postsynaptic calcium signalling is constrained by a thin near-membrane cistern that is co-extensive with the efferent terminal contacts. The postsynaptic cistern may play an essential role in calcium homeostasis, serving as sink or source, depending on ongoing activity and the degree of buffer saturation. Release of calcium from postsynaptic stores leads to a process of retrograde facilitation via the synthesis of nitric oxide in the hair cell. Activity-dependent synaptic modification may contribute to changes in hair cell innervation that occur during development, and in the aged or damaged cochlea. PMID:24566542

  19. Divergent cytosine DNA methylation patterns in single-cell, soybean root hairs.

    PubMed

    Hossain, Md Shakhawat; Kawakatsu, Taiji; Kim, Kyung Do; Zhang, Ning; Nguyen, Cuong T; Khan, Saad M; Batek, Josef M; Joshi, Trupti; Schmutz, Jeremy; Grimwood, Jane; Schmitz, Robert J; Xu, Dong; Jackson, Scott A; Ecker, Joseph R; Stacey, Gary

    2017-04-01

    Chromatin modifications, such as cytosine methylation of DNA, play a significant role in mediating gene expression in plants, which affects growth, development, and cell differentiation. As root hairs are single-cell extensions of the root epidermis and the primary organs for water uptake and nutrients, we sought to use root hairs as a single-cell model system to measure the impact of environmental stress. We measured changes in cytosine DNA methylation in single-cell root hairs as compared with multicellular stripped roots, as well as in response to heat stress. Differentially methylated regions (DMRs) in each methylation context showed very distinct methylation patterns between cell types and in response to heat stress. Intriguingly, at normal temperature, root hairs were more hypermethylated than were stripped roots. However, in response to heat stress, both root hairs and stripped roots showed hypomethylation in each context, especially in the CHH context. Moreover, expression analysis of mRNA from similar tissues and treatments identified some associations between DMRs, genes and transposons. Taken together, the data indicate that changes in DNA methylation are directly or indirectly associated with expression of genes and transposons within the context of either specific tissues/cells or stress (heat). © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  20. Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

    PubMed Central

    Zhen, Hanson H.; Oro, Anthony E.

    2013-01-01

    Hair follicle morphogenesis, a complex process requiring interaction between epithelia-derived keratinocytes and the underlying mesenchyme, is an attractive model system to study organ development and tissue-specific signaling. Although hair follicle development is genetically tractable, fast and reproducible analysis of factors essential for this process remains a challenge. Here we describe a procedure to generate targeted overexpression or shRNA-mediated knockdown of factors using lentivirus in a tissue-specific manner. Using a modified version of a hair regeneration model 5, 6, 11, we can achieve robust gain- or loss-of-function analysis in primary mouse keratinocytes or dermal cells to facilitate study of epithelial-mesenchymal signaling pathways that lead to hair follicle morphogenesis. We describe how to isolate fresh primary mouse keratinocytes and dermal cells, which contain dermal papilla cells and their precursors, deliver lentivirus containing either shRNA or cDNA to one of the cell populations, and combine the cells to generate fully formed hair follicles on the backs of nude mice. This approach allows analysis of tissue-specific factors required to generate hair follicles within three weeks and provides a fast and convenient companion to existing genetic models. PMID:23486463

  1. Hair restoration surgery: challenges and solutions

    PubMed Central

    Rose, Paul T

    2015-01-01

    Hair loss is a common problem affecting both men and women. The most frequent etiology is androgenetic alopecia, but other causes of hair loss such as trauma, various dermatologic diseases, and systemic diseases can cause alopecia. The loss of hair can have profound effects on one’s self esteem and emotional well-being, as one’s appearance plays a role in the work place and interpersonal relationships. It is therefore not surprising that means to remedy hair loss are widely sought. Hair transplant surgery has become increasingly popular, and the results that we are able to create today are quite remarkable, providing a natural appearance when the procedure is performed well. In spite of this, hair transplant surgery is not perfect. It is not perfect because the hair transplant surgeon is still faced with challenges that prevent the achievement of optimal results. Some of these challenges include a limit to donor hair availability, hair survival, and ways to conceal any evidence of a surgical procedure having taken place. This article examines some of the most important challenges facing hair restoration surgery today and possible solutions to these challenges. PMID:26203266

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

    PubMed

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

    2016-05-03

    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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Bulge Region as a Putative Hair Follicle Stem Cells Niche: A Brief Review

    PubMed Central

    JOULAI VEIJOUYE, Sanaz; YARI, Abazar; HEIDARI, Fatemeh; SAJEDI, Nayereh; GHOROGHI MOGHANI, Fatemeh; NOBAKHT, Maliheh

    2017-01-01

    Background: Hair follicle stem cells exist in different sites. Most of the hair follicle stem cells are reside in niche called bulge. Bulge region is located between the opening of sebaceous gland and the attachment site of the arrector pili muscle. Methods: Data were collected using databases and resources of PubMed, Web of Science, Science Direct, Scopus, MEDLINE and their references from the earliest available published to identify English observational studies on hair follicle bulge region. Results: Bulge stem cells are pluripotent with high proliferative capacity. Specific markers allow the bulge cells to be isolated from mouse or human hair follicle. Stem cells isolated from bulge region are label retaining and slow cycling hence these cells are defined as label-retaining cells. Bulge cell populations, due to their plasticity nature are able to differentiate into distinct linage and could contribute in tissue regeneration. Conclusion: The current review discuss about bulge stem cells characteristics and biology including their cycle, location, plasticity, specific markers and regenerative nature. Also the differences between mouse and human hair follicles are investigated. PMID:29026781

  4. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.

    PubMed

    Peterson, Shelby C; Eberl, Markus; Vagnozzi, Alicia N; Belkadi, Abdelmadjid; Veniaminova, Natalia A; Verhaegen, Monique E; Bichakjian, Christopher K; Ward, Nicole L; Dlugosz, Andrzej A; Wong, Sunny Y

    2015-04-02

    Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches

    PubMed Central

    Peterson, Shelby C.; Eberl, Markus; Vagnozzi, Alicia N.; Belkadi, Abdelmadjid; Veniaminova, Natalia A.; Verhaegen, Monique E.; Bichakjian, Christopher K.; Ward, Nicole L.; Dlugosz, Andrzej A.; Wong, Sunny Y.

    2015-01-01

    SUMMARY Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well-established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as “hot spots” for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis. PMID:25842978

  6. Cell membrane organization is important for inner hair cell MET-channel gating

    NASA Astrophysics Data System (ADS)

    Effertz, Thomas; Scharr, Alexandra L.; Ricci, Anthony J.

    2018-05-01

    Specialized sensory cells, hair cells, translate mechanical stimuli into electro/chemical responses. This process, termed mechano-electrical transduction (MET), is localized to the hair cell's sensory organelle, the hair bundle. The mature hair bundle comprises three rows of actin filled stereocilia, arranged in a staircase pattern. Deflections towards the tallest row of stereocilia activate MET channels, residing at the top of stereocilia. While other MET channels can be activated or modulated by changes to their lipid environment, this remains unknown for the mammalian auditory MET channel. We show here that the effect of lipid and cholesterol depletion from the cell membrane affect the MET current as well. We used γ-cyclodextrin to extract lipids form the membrane, reversibly reducing the peak MET current, current adaptation, and decreasing the channels resting open probability. The recovery after γ-cyclodextrin treatment was slower than the initial peak current reduction, suggesting that a specific lipid organization is required for normal MET channel function, which requires time reestablish. Extraction of cholesterol, using Mβ-cyclodextrin, irreversibly reduces the peak MET current and reversibly increases the channel resting open probability, suggesting that cholesterol restricts MET channel opening. This restriction could be useful to increase the channel's signal to noise ratio. Together this data suggests that the cell membrane is part of the force relay machinery to the MET channel and could possibly restrict gating associated conformational changes of the MET channel.

  7. Actin polymerization drives polar growth in Arabidopsis root hair cells.

    PubMed

    Vazquez, Luis Alfredo Bañuelos; Sanchez, Rosana; Hernandez-Barrera, Alejandra; Zepeda-Jazo, Isaac; Sánchez, Federico; Quinto, Carmen; Torres, Luis Cárdenas

    2014-01-01

    In plants, the actin cytoskeleton is a prime regulator of cell polarity, growth, and cytoplasmic streaming. Tip growth, as observed in root hairs, caulonema, and pollen tubes, is governed by many factors, including calcium gradients, exocytosis and endocytosis, reactive oxygen species, and the cytoskeleton. Several studies indicate that the polymerization of G-actin into F-actin also contributes to tip growth. The structure and function of F-actin within the apical dome is variable, ranging from a dense meshwork to sparse single filaments. The presence of multiple F-actin structures in the elongating apices of tip-growing cells suggests that this cytoskeletal array is tightly regulated. We recently reported that sublethal concentrations of fluorescently labeled cytochalasin could be used to visualize the distribution of microfilament plus ends using fluorescence microscopy, and found that the tip region of the growing root hair cells of a legume plant exhibits a clear response to the nodulation factors secreted by Rhizobium. (1) In this current work, we expanded our analysis using confocal microscopy and demonstrated the existence of highly dynamic fluorescent foci along Arabidopsis root hair cells. Furthermore, we show that the strongest fluorescence signal accumulates in the tip dome of the growing root hair and seems to be in close proximity to the apical plasma membrane. Based on these findings, we propose that actin polymerization within the dome of growing root hair cells regulates polar growth.

  8. Preclinical and Clinical Studies Demonstrate That the Proprietary Herbal Extract DA-5512 Effectively Stimulates Hair Growth and Promotes Hair Health.

    PubMed

    Yu, Jae Young; Gupta, Biki; Park, Hyoung Geun; Son, Miwon; Jun, Joon-Ho; Yong, Chul Soon; Kim, Jeong Ah; Kim, Jong Oh

    2017-01-01

    The proprietary DA-5512 formulation comprises six herbal extracts from traditional oriental plants historically associated with therapeutic and other applications related to hair. Here, we investigated the effects of DA-5512 on the proliferation of human dermal papilla cells (hDPCs) in vitro and on hair growth in C57BL/6 mice and conducted a clinical study to evaluate the efficacy and safety of DA-5512. DA-5512 significantly enhanced the viability of hDPCs in a dose-dependent manner ( p < 0.05), and 100 ppm of DA-5512 and 1  μ M minoxidil (MXD) significantly increased the number of Ki-67-positive cells, compared with the control group ( p < 0.05). MXD (3%) and DA-5512 (1%, 5%) significantly stimulated hair growth and increased the number and length of hair follicles (HFs) versus the controls (each p < 0.05). The groups treated with DA-5512 exhibited hair growth comparable to that induced by MXD. In clinical study, we detected a statistically significant increase in the efficacy of DA-5512 after 16 weeks compared with the groups treated with placebo or 3% MXD ( p < 0.05). In conclusion, DA-5512 might promote hair growth and enhance hair health and can therefore be considered an effective option for treating hair loss.

  9. Damage and Recovery of Hair Cells in Fish Canal (But Not Superficial) Neuromasts after Gentamicin Exposure

    NASA Technical Reports Server (NTRS)

    Song, Jiakun; Yan, Hong Young; Popper, Arthur N.

    1995-01-01

    Recent evidence demonstrating the presence of two types of sensory hair cells in the ear of a telcost fish (Astronotus ocellatus, the oscar) indicates that hair cell heterogeneity may exist not only in amniotic vertebrates but also in anamniotes. Here we report that a similar heterogeneity between hair cell types may also occur in the other mechanosensory organ of the oscar, the lateral line. We exposed oscars to the aminoglycoside (ototoxic) antibiotic gentamicin sulfate and found damaged sensory hair cells in one class of the lateral line receptors, the canal neuromasts, but not in the other class, the superficial neuromasts. This effect was not due to the canal environment. Moreover, new ciliary bundles on hair cells of the canal neuromasts were found after, and during, gentamicin exposure. The pattern of hair cell destruction and recovery in canal neuromasts is similar to that of type 1-like hair cells found in the striolar region of the utricle and lagena of the oscar after gentamicin treatment. These results suggest that the hair cells in the canal and superficial neuromasts may be similar to type 1-like and type 2 hair cells, respectively, in the fish ear.

  10. Post-transcriptional Regulation of Keratinocyte Progenitor Cell Expansion, Differentiation and Hair Follicle Regression by miR-22

    PubMed Central

    Meng, Qingyong; Zhao, Yiqiang; Chen, Lei; Zhang, Hongquan; Xue, Lixiang; Zhang, Xiuqing; Lengner, Christopher; Yu, Zhengquan

    2015-01-01

    Hair follicles (HF) undergo precisely regulated recurrent cycles of growth, cessation, and rest. The transitions from anagen (growth), to catagen (regression), to telogen (rest) involve a physiological involution of the HF. This process is likely coordinated by a variety of mechanisms including apoptosis and loss of growth factor signaling. However, the precise molecular mechanisms underlying follicle involution after hair keratinocyte differentiation and hair shaft assembly remain poorly understood. Here we demonstrate that a highly conserved microRNA, miR-22 is markedly upregulated during catagen and peaks in telogen. Using gain- and loss-of-function approaches in vivo, we find that miR-22 overexpression leads to hair loss by promoting anagen-to-catagen transition of the HF, and that deletion of miR-22 delays entry to catagen and accelerates the transition from telogen to anagen. Ectopic activation of miR-22 results in hair loss due to the repression a hair keratinocyte differentiation program and keratinocyte progenitor expansion, as well as promotion of apoptosis. At the molecular level, we demonstrate that miR-22 directly represses numerous transcription factors upstream of phenotypic keratin genes, including Dlx3, Foxn1, and Hoxc13. We conclude that miR-22 is a critical post-transcriptional regulator of the hair cycle and may represent a novel target for therapeutic modulation of hair growth. PMID:26020521

  11. Lactate dehydrogenase activity drives hair follicle stem cell activation

    PubMed Central

    Aimee, Flores; John, Schell; Abby, Krall; David, Jelinek; Matilde, Miranda; Melina, Grigorian; Daniel, Braas; White Andrew, C; Jessica, Zhou; Nick, Graham; Thomas, Graeber; Pankaj, Seth; Denis, Evseenko; Hilary, Coller; Jared, Rutter; Heather, Christofk; Lowry William, E

    2017-01-01

    Summary While normally dormant, Hair Follicle Stem Cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allow them to remain dormant and yet quickly respond to appropriate proliferative stimuli. PMID:28812580

  12. Synchronization of Spontaneous Active Motility of Hair Cell Bundles

    PubMed Central

    Zhang, Tracy-Ying; Ji, Seung; Bozovic, Dolores

    2015-01-01

    Hair cells of the inner ear exhibit an active process, believed to be crucial for achieving the sensitivity of auditory and vestibular detection. One of the manifestations of the active process is the occurrence of spontaneous hair bundle oscillations in vitro. Hair bundles are coupled by overlying membranes in vivo; hence, explaining the potential role of innate bundle motility in the generation of otoacoustic emissions requires an understanding of the effects of coupling on the active bundle dynamics. We used microbeads to connect small groups of hair cell bundles, using in vitro preparations that maintain their innate oscillations. Our experiments demonstrate robust synchronization of spontaneous oscillations, with either 1:1 or multi-mode phase-locking. The frequency of synchronized oscillation was found to be near the mean of the innate frequencies of individual bundles. Coupling also led to an improved regularity of entrained oscillations, demonstrated by an increase in the quality factor. PMID:26540409

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

    PubMed Central

    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 that extend laterally from the hair cell’s base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells range in shape, size, and branching, with the longest processes extending 3–4 hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Further, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network amongst type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3–6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells, and they suggest type II hair cells may directly communicate with each other, which has not been described in vertebrates. PMID:24825750

  14. Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death

    PubMed Central

    Kenyon, Emma J.; Kirkwood, Nerissa K.; Kitcher, Siân R.; O’Reilly, Molly; Cantillon, Daire M.; Goodyear, Richard J.; Secker, Abigail; Baxendale, Sarah; Bull, James C.; Waddell, Simon J.; Whitfield, Tanya T.; Ward, Simon E.; Kros, Corné J.; Richardson, Guy P.

    2017-01-01

    Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red–conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem. PMID:29263311

  15. Identification of ion-channel modulators that protect against aminoglycoside-induced hair cell death.

    PubMed

    Kenyon, Emma J; Kirkwood, Nerissa K; Kitcher, Siân R; O'Reilly, Molly; Derudas, Marco; Cantillon, Daire M; Goodyear, Richard J; Secker, Abigail; Baxendale, Sarah; Bull, James C; Waddell, Simon J; Whitfield, Tanya T; Ward, Simon E; Kros, Corné J; Richardson, Guy P

    2017-12-21

    Aminoglycoside antibiotics are used to treat life-threatening bacterial infections but can cause deafness due to hair cell death in the inner ear. Compounds have been described that protect zebrafish lateral line hair cells from aminoglycosides, but few are effective in the cochlea. As the aminoglycosides interact with several ion channels, including the mechanoelectrical transducer (MET) channels by which they can enter hair cells, we screened 160 ion-channel modulators, seeking compounds that protect cochlear outer hair cells (OHCs) from aminoglycoside-induced death in vitro. Using zebrafish, 72 compounds were identified that either reduced loading of the MET-channel blocker FM 1-43FX, decreased Texas red-conjugated neomycin labeling, or reduced neomycin-induced hair cell death. After testing these 72 compounds, and 6 structurally similar compounds that failed in zebrafish, 13 were found that protected against gentamicin-induced death of OHCs in mouse cochlear cultures, 6 of which are permeant blockers of the hair cell MET channel. None of these compounds abrogated aminoglycoside antibacterial efficacy. By selecting those without adverse effects at high concentrations, 5 emerged as leads for developing pharmaceutical otoprotectants to alleviate an increasing clinical problem.

  16. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

    PubMed

    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. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  17. Effects of hydrogen peroxide on vestibular hair cells in the guinea pig: importance of cell membrane impairment preceding cell death.

    PubMed

    Tanigawa, Tohru; Tanaka, Hirokazu; Hayashi, Ken; Nakayama, Meiho; Iwasaki, Satoshi; Banno, Shinya; Takumida, Masaya; Brodie, Hirally; Inafuku, Shigeru

    2008-11-01

    Our findings indicate that oxidative stress induces morphological changes in vestibular hair cells and subsequently leads to cell death after 2.5 h. The aim of this study was to confirm the direct effects of oxidative stress on vestibular hair cells. Vestibular hair cells isolated from guinea pigs were loaded with 1 or 10 mM H2O2, and morphological changes were observed. In addition, in a viability/cytotoxicity assay system, the numbers of dead cells in isolated cristae ampullares were counted 1, 3, and 5 h after loading with H2O2 or artificial perilymph (control). Reactive oxygen, in the form of H2O2, directly affects the cell membrane of isolated vestibular hair cells and causes swelling of the cell body, bleb formation, and shortening of the neck region. Morphological changes occur within 30 min after loading with H2O2, but a significant increase in the number of dead cells is noted only after 3 h.

  18. Stimulus dependent properties of mammalian cochlear hair cell mechanoelectrical transduction

    NASA Astrophysics Data System (ADS)

    Scharr, A. L.; Ricci, Anthony

    2018-05-01

    Cochlear hair cell stereocilia move semi-independently, shaping the force transfer to mechanoelectrical transduction (MET) channels, as indicated by the MET current response. Semi-independent movement of stereocilia was evoked by stimulating inner hair cell (IHC) bundles from acutely dissected rat cochlea with stiff probes ranging in size from 1 to 10 µm. MET current responses were recorded using whole-cell patch-clamp electrophysiology. Small probes directly displaced stereocilia they contacted, and recruited adjacent stereocilia depending on stimulus magnitude. We inferred that the recruitment of stereocilia resulted in less uniform and less synchronous movement. Step displacements using smaller probes resulted in smaller current responses (from 1 nA for large probes to 0.3 nA for small, p <.0001), slower rate of current activation, as measured from the linear portion (from 4 nA/ms to 1 nA/ms, p <.0001), slower time constants of adaptation, as measured from double exponential fits from peak to steady state current (fast component: from 0.6 to 1.2 ms, p =.004; slow component: from 8 ms to 12 ms, p =.001) and less complete adaptation (from 95% to 30%, p <.0001). These results indicate that the mechanical properties of less coherent bundles greatly affect force transfer to MET channels as indicated by the electrical response of the cell. Thus, outer hair cells (OHCs), with their bundles embedded in the tectorial membrane, may exhibit synchronous MET activation and therefore time-dependent adaptation where fast adaptation provides a high pass filter. Hair cells with free standing bundles, like inner hair cells (IHC), may exhibit more asynchronous MET activation and adaptation, in which case adaptation would not provide this additional filter.

  19. Ethanol affects the development of sensory hair cells in larval zebrafish (Danio rerio).

    PubMed

    Uribe, Phillip M; Asuncion, James D; Matsui, Jonathan I

    2013-01-01

    Children born to mothers with substantial alcohol consumption during pregnancy can present a number of morphological, cognitive, and sensory abnormalities, including hearing deficits, collectively known as fetal alcohol syndrome (FAS). The goal of this study was to determine if the zebrafish lateral line could be used to study sensory hair cell abnormalities caused by exposure to ethanol during embryogenesis. Some lateral line sensory hair cells are present at 2 days post-fertilization (dpf) and are functional by 5 dpf. Zebrafish embryos were raised in fish water supplemented with varying concentrations of ethanol (0.75%-1.75% by volume) from 2 dpf through 5 dpf. Ethanol treatment during development resulted in many physical abnormalities characteristic of FAS in humans. Also, the number of sensory hair cells decreased as the concentration of ethanol increased in a dose-dependent manner. The dye FM 1-43FX was used to detect the presence of functional mechanotransduction channels. The percentage of FM 1-43-labeled hair cells decreased as the concentration of ethanol increased. Methanol treatment did not affect the development of hair cells. The cell cycle markers proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) demonstrated that ethanol reduced the number of sensory hair cells, as a consequence of decreased cellular proliferation. There was also a significant increase in the rate of apoptosis, as determined by TUNEL-labeling, in neuromasts following ethanol treatment during larval development. Therefore, zebrafish are a useful animal model to study the effects of hair cell developmental disorders associated with FAS.

  20. Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy.

    PubMed

    Sharova, Tatyana Y; Poterlowicz, Krzysztof; Botchkareva, Natalia V; Kondratiev, Nikita A; Aziz, Ahmar; Spiegel, Jeffrey H; Botchkarev, Vladimir A; Sharov, Andrey A

    2014-12-01

    Chemotherapy has severe side effects in normal rapidly proliferating organs, such as hair follicles, 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 (DXR), and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in DXR-treated hair follicles versus controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptors 1/2), as well as of a large number of keratin-associated protein genes, were seen after DXR treatment. Hair follicle apoptosis induced by DXR was significantly inhibited by either TRAIL-neutralizing antibody or caspase-8 inhibitor, thus suggesting a previously unreported role for TRAIL receptor signaling in mediating DXR-induced hair loss. These data demonstrate that the early phase of the hair follicle response to DXR includes upregulation of apoptosis-associated markers, as well as substantial reorganization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies toward the design of effective approaches for the management of chemotherapy-induced hair loss.

  1. Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy

    PubMed Central

    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 follicles versus the controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL receptors 1/2), as well as of a large number of the keratin-associated protein genes were seen after doxorubicin treatment. Hair follicle apoptosis induced by doxorubicin was significantly inhibited by either TRAIL neutralizing antibody or caspase 8 inhibitor, thus suggesting a novel role for TRAIL receptor signaling in mediating doxorubicin-induced hair loss. These data demonstrate that the early phase of the hair follicle response to doxorubicin includes upregulation of apoptosis-associated markers, as well as substantial re-organization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies towards the design of novel approaches for management of chemotherapy-induced hair loss. PMID:24999588

  2. Magnetic actuation of hair cells

    NASA Astrophysics Data System (ADS)

    Rowland, David; Roongthumskul, Yuttana; Lee, Jae-Hyun; Cheon, Jinwoo; Bozovic, Dolores

    2011-11-01

    The bullfrog sacculus contains mechanically sensitive hair cells whose stereociliary bundles oscillate spontaneously when decoupled from the overlying membrane. Steady-state offsets on the resting position of a hair bundle can suppress or modulate this native motility. To probe the dynamics of spontaneous oscillation in the proximity of the critical point, we describe here a method for mechanical actuation that avoids loading the bundles or contributing to the viscous drag. Magnetite beads were attached to the tips of the stereocilia, and a magnetic probe was used to impose deflections. This technique allowed us to observe the transition from multi-mode to single-mode state in freely oscillating bundles, as well as the crossover from the oscillatory to the quiescent state.

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

    PubMed Central

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

    2016-01-01

    Bioengineering hair follicles using cells isolated from human tissue remains as 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 chemical factors, including WNT and BMP molecules, to maintain the hair inductive property. CD133 is expressed by a small 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 two-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 than control cells. Further analysis showed that matrix cell proliferation and differentiation were significantly promoted in hair follicles when β-catenin signaling was upregulated 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

  4. African american women, hair care, and health barriers.

    PubMed

    Gathers, Raechele Cochran; Mahan, Meredith Grace

    2014-09-01

    The objective of this study was to elucidate the prevalence of hair loss among African American women; explore the psychosocial impact of hair grooming difficulties; and examine both perceptions related to physician encounters in this group and the relationship between hair grooming, physical activity, and weight maintenance. An anonymous retrospective and qualitative survey, the Hair Care Assessment Survey, is an 18-question novel survey instrument designed at the Henry Ford Hospital Department of Dermatology Multicultural Dermatology Center. The Hair Care Assessment Survey was distributed at church-related functions at predominantly African American metropolitan Detroit churches. Two hundred African American women from metropolitan Detroit, Michigan, aged 21 to 83. The Hair Care Assessment Survey collected data relating to hair loss and hair care, psychosocial experiences relating to hair loss, and hair care as it relates to exercise and body weight management. Data was collected on doctor-patient hair-related medical visits and experiences with commercially available ethnic hair care products. More than 50 percent reported excessive hair loss. Twenty-eight percent had visited a physician to discuss hair issues, but only 32 percent felt their physician understood African American hair. Forty-five percent reported avoiding exercise because of hair concerns, and 22 percent felt that their hair impeded maintaining healthy body weight. Hair loss affects a compelling number of African American women, and a significant number express dissatisfaction in hair-related physician encounters. Additionally, hair styling problems present a serious impediment to physical activity and weight management among this already high-risk population.

  5. African American Women, Hair Care, and Health Barriers

    PubMed Central

    Mahan, Meredith Grace

    2014-01-01

    Objectives: The objective of this study was to elucidate the prevalence of hair loss among African American women; explore the psychosocial impact of hair grooming difficulties; and examine both perceptions related to physician encounters in this group and the relationship between hair grooming, physical activity, and weight maintenance. Design: An anonymous retrospective and qualitative survey, the Hair Care Assessment Survey, is an 18-question novel survey instrument designed at the Henry Ford Hospital Department of Dermatology Multicultural Dermatology Center. Setting: The Hair Care Assessment Survey was distributed at church-related functions at predominantly African American metropolitan Detroit churches. Participants: Two hundred African American women from metropolitan Detroit, Michigan, aged 21 to 83. Measurements: The Hair Care Assessment Survey collected data relating to hair loss and hair care, psychosocial experiences relating to hair loss, and hair care as it relates to exercise and body weight management. Data was collected on doctor-patient hair-related medical visits and experiences with commercially available ethnic hair care products. Results: More than 50 percent reported excessive hair loss. Twenty-eight percent had visited a physician to discuss hair issues, but only 32 percent felt their physician understood African American hair. Forty-five percent reported avoiding exercise because of hair concerns, and 22 percent felt that their hair impeded maintaining healthy body weight. Conclusion: Hair loss affects a compelling number of African American women, and a significant number express dissatisfaction in hair-related physician encounters. Additionally, hair styling problems present a serious impediment to physical activity and weight management among this already high-risk population. PMID:25276273

  6. Effect of Cinnamomum osmophloeum Kanehira Leaf Aqueous Extract on Dermal Papilla Cell Proliferation and Hair Growth

    PubMed Central

    Wen, Tung-Chou; Li, Yuan-Sheng; Rajamani, Karthyayani; Harn, Horng-Jyh; Lin, Shinn-Zong; Chiou, Tzyy-Wen

    2018-01-01

    In this study, we explored the effect of the water extract of Cinnamomum osmophloeum Kanehira (COK) leaves on hair growth by in vitro and in vivo assays. Using an in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, it was found that the proliferation of rat vibrissae and human hair dermal papilla cells (hDPCs) was significantly enhanced by the COK leaf extract treatment. As determined by quantitative real-time polymerase chain reaction (RT-PCR), the messenger RNA (mRNA) levels of some hair growth–related factors including vascular endothelial growth factor, keratinocyte growth factor (KGF), and transforming growth factor-β2 were found to be higher in the cultured hDPCs exposed to COK leaf extract than those in the untreated control group. In the hair-depilated C57BL/6 mouse model, the stimulation of hair growth was demonstrated in the group of COK leaf extract treatment. Both photographical and histological observations revealed the promotion of the anagen phase in the hair growth cycle by the COK leaf extract in the C57BL/6 mice. Finally, the ultra performance liquid chromatography (UPLC) showed that the COK extract contained mostly cinnamic aldehyde and a small amount of cinnamic acid. The results suggest that the COK leaf extract may find use for the treatment of hair loss. PMID:29637818

  7. Regeneration of Sensory Hair Cells Requires Localized Interactions between the Notch and Wnt Pathways.

    PubMed

    Romero-Carvajal, Andrés; Navajas Acedo, Joaquín; Jiang, Linjia; Kozlovskaja-Gumbrienė, Agnė; Alexander, Richard; Li, Hua; Piotrowski, Tatjana

    2015-08-10

    In vertebrates, mechano-electrical transduction of sound is accomplished by sensory hair cells. Whereas mammalian hair cells are not replaced when lost, in fish they constantly renew and regenerate after injury. In vivo tracking and cell fate analyses of all dividing cells during lateral line hair cell regeneration revealed that support and hair cell progenitors localize to distinct tissue compartments. Importantly, we find that the balance between self-renewal and differentiation in these compartments is controlled by spatially restricted Notch signaling and its inhibition of Wnt-induced proliferation. The ability to simultaneously study and manipulate individual cell behaviors and multiple pathways in vivo transforms the lateral line into a powerful paradigm to mechanistically dissect sensory organ regeneration. The striking similarities to other vertebrate stem cell compartments uniquely place zebrafish to help elucidate why mammals possess such low capacity to regenerate hair cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Efficacy and Safety of Minoxidil 2% Solution in Combination With a Botanical Hair Solution in Women With Female Pattern Hair Loss/Androgenic Alopecia.

    PubMed

    McMichael, Amy; Pham, Hanh; von Grote, Erika; Meckfessel, Matthew H

    2016-04-01

    Female pattern hair loss (FPHL), also known as female androgenic alopecia, affects over 21 million women in the United States with devastating effects on self-esteem and psychosocial functioning. Topical minoxidil 2% and 5% formulations are the only US Food and Drug Administration-approved treatments for FPHL. The length of time it typically takes to observe the benefits is a challenge for many patients, and may affect adherence to treatment. Herbal extracts, which are also believed to promote healthier-looking hair, have a long history of use in hair care formulations. The safety and efficacy of a twice-daily regimen of 2% minoxidil solution used in combination with the botanical hair solution for 12 weeks in 54 subjects was evaluated in a multicenter, single-arm, open-label study. Assessments included investigator and subject ratings of improvement and subject satisfaction. Investigator ratings indicated significant improvement in hair growth and overall treatment benefits in as early as 6 weeks (P<.001). Subject self-ratings indicated significant satisfaction with hair volume and quality improvement at week 6 (P<.001). Subjects also indicated an increase in self-confidence and attractiveness at week 12 (P<.001). The investigator and subject-assessed efficacy and subject satisfaction with this regimen provides clinicians with an effective treatment option for FPHL that also provides a high level of patient acceptance, which ultimately may help promote minoxidil treatment adherence.

  9. The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial.

    PubMed

    Gentile, Pietro; Garcovich, Simone; Bielli, Alessandra; Scioli, Maria Giovanna; Orlandi, Augusto; Cervelli, Valerio

    2015-11-01

    Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, we report the results of a randomized, evaluator-blinded, placebo-controlled, half-head group study to compare, with the aid of computerized trichograms, hair regrowth with PRP versus placebo. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. PRP, prepared from a small volume of blood, was injected on half of the selected patients' scalps with pattern hair loss. The other half was treated with placebo. Three treatments were administered to each patient at 30-day intervals. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki67 evaluation. Patients were followed for 2 years. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area, and a mean increase in total hair density of 45.9 hairs per cm² compared with baseline values. No side effects were noted during treatment. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles 2 weeks after the last PRP treatment compared with baseline value (p < .05). We also observed an increase of Ki67(+) keratinocytes in the epidermis and of hair follicular bulge cells, and a slight increase of small blood vessels around hair follicles in the treated skin compared with baseline (p < .05). Relapse of androgenic alopecia was not evaluated in all patients until 12 months after the last treatment. After 12 months, 4 patients reported progressive hair loss; this was more evident 16 months after the last treatment. Those four patients were re-treated. Our data clearly highlight the positive effects of PRP

  10. A missense mutation in myosin VIIA prevents aminoglycoside accumulation in early postnatal cochlear hair cells.

    PubMed

    Richardson, G P; Forge, A; Kros, C J; Marcotti, W; Becker, D; Williams, D S; Thorpe, J; Fleming, J; Brown, S D; Steel, K P

    1999-11-28

    Myosin VIIA is expressed by sensory hair cells in the inner ear and proximal tubule cells in the kidney, the two primary targets of aminoglycoside antibiotics. Using cochlear cultures prepared from early postnatal Myo7a6J mice with a missense mutation in the head region of the myosin VIIA molecule we show that this myosin is required for aminoglycoside accumulation in cochlear hair cells. Hair cells in homozygous mutant Myo7a6J cochlear cultures have disorganized hair bundles, but are otherwise morphologically normal and transduce. However, and in contrast to hair cells from heterozygous Myo7a6J cultures, the homozygous Myo7a6J hair cells do not accumulate [3H]gentamicin and do not exhibit an ototoxic response on exposure to aminoglycoside. Possible roles for myosin VIIA in the process of aminoglycoside accumulation are discussed.

  11. Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro.

    PubMed

    Jia, Zhanwei; He, Qiang; Shan, Chunguang; Li, Fengyi

    2018-09-15

    Gentamycin is one of the most clinically used aminoglycoside antibiotics which induce intrinsic apoptosis of hair cells. Tauroursodeoxycholic acid (TUDCA) is known as safe cell-protective agent in disorders associated with apoptosis. We aimed to investigate the protective effects of TUDCA against gentamicin-induced ototoxicity. House Ear Institute-Organ of Corti 1(HEI-OC1) cells and explanted cochlear tissue were treated with gentamicin and TUDCA, followed by serial analyses including cell viability assay, hair cell staining, qPCR, ELISA and western blotting to determine the cell damage by the parameters relevant to cell apoptosis and endoplasmic reticulum stress. TUDCA significantly attenuated gentamicin-induced cell damage in cultured HEI-OC1 cells and explanted cochlear hair cells. TUDCA alleviated gentamicin-induced cell apoptosis, supported by the decreased Bax/Bcl2 ratio compared with that of gentamicin treated alone. TUDCA decreased gentamicin-induced nitric oxide production and protein nitration in both models. In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. New multi-targeting strategy in hair growth promotion: in vitro and in vivo studies.

    PubMed

    Marzani, Barbara; Pinto, Daniela; Sorbellini, Elisabetta; Rinaldi, Fabio

    2018-06-01

    Considering the importance of hair in our modern society and the impact of hair loss, the efforts of researchers are addressed to better understand the mechanisms behind the hair cycle regulation and dysregulation. Because hair loss is multifactorial, differenced and new approaches are required. In particular we addressed our attention to two recently identified targets in hair cycling and growth control: olfactory receptor and autophagy. The aim of the study was to evaluate: the possible pro-autophagic effect of N1-methylspermidine (a spermidine analogue) in vitro and, in a double blind clinical trial, the safety and efficacy of topical daily application of a lotion containing N1-methylspermidine and Sandalore®. Autophagic modulation by N1-methylspermidine was monitored in vitro by LC3 and p62 fluorescent signal cell line. Topical daily application of the lotion was tested in 60 male and female subjects with chronic telogen effluvium by means of non-invasive objective evaluation. The results obtained by in vitro tests showed the capacity of N1-methylspermidine to increase autophagic process while the clinical trials performed confirmed the safety and anti hair loss efficacy of the lotion reporting a reduction of hair loss (modified wash test) and hair growth stimulation as evaluated by hair density, hair shaft diameter, % of anagen hair and Hair Mass Index increase after 3 months of treatment. The lotion efficacy remained statistically significant for the above-mentioned parameters, with the exception of hair lost during wash, also 3 months after the end of treatment. Based on the obtained results, the daily use of the N1-methylspermidine and Sandalore®-based lotion is efficient to counteract hair loss and increase hair growth by a multifunctional targeting approach.

  13. Mutations in cadherin 23 affect tip links in zebrafish sensory hair cells.

    PubMed

    Söllner, Christian; Rauch, Gerd-Jörg; Siemens, Jan; Geisler, Robert; Schuster, Stephan C; Müller, Ulrich; Nicolson, Teresa

    2004-04-29

    Hair cells have highly organized bundles of apical projections, or stereocilia, that are deflected by sound and movement. Displacement of stereocilia stretches linkages at the tips of stereocilia that are thought to gate mechanosensory channels. To identify the molecular machinery that mediates mechanotransduction in hair cells, zebrafish mutants were identified with defects in balance and hearing. In sputnik mutants, stereociliary bundles are splayed to various degrees, with individuals displaying reduced or absent mechanotransduction. Here we show that the defects in sputnik mutants are caused by mutations in cadherin 23 (cdh23). Mutations in Cdh23 also cause deafness and vestibular defects in mice and humans, and the protein is present in hair bundles. We show that zebrafish Cdh23 protein is concentrated near the tips of hair bundles, and that tip links are absent in homozygous sputnik(tc317e) larvae. Moreover, tip links are absent in larvae carrying weak alleles of cdh23 that affect mechanotransduction but not hair bundle integrity. We conclude that Cdh23 is an essential tip link component required for hair-cell mechanotransduction.

  14. ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

    PubMed

    Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R; Jobling, Phillip; Callister, Robert J; Migliaccio, Americo A; Jordan, Paivi M; Holt, Joseph C; Rabbitt, Richard D; Lim, Rebecca; Brichta, Alan M

    2018-01-01

    In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 -/- ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 -/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted

  15. A PAIR OF TRANSMEMBRANE RECEPTORS ESSENTIAL FOR THE RETENTION AND PIGMENTATION OF HAIR

    PubMed Central

    Han, Rong; Beppu, Hideyuki; Lee, Yun-Kyoung; Georgopoulos, Katia; Larue, Lionel; Li, En; Weiner, Lorin; Brissette, Janice L.

    2012-01-01

    Hair follicles are simple, accessible models for many developmental processes. Here, using mutant mice, we show that Bmpr2, a known receptor for bone morphogenetic proteins (Bmps), and Acvr2a, a known receptor for Bmps and activins, are individually redundant but together essential for multiple follicular traits. When Bmpr2/Acvr2a function is reduced in cutaneous epithelium, hair follicles undergo rapid cycles of hair generation and loss. Alopecia results from a failure to terminate hair development properly, as hair clubs never form, and follicular retraction is slowed. Hair regeneration is rapid due to premature activation of new hair-production programs. Hair shafts differentiate aberrantly due to impaired arrest of medullary-cell proliferation. When Bmpr2/Acvr2a function is reduced in melanocytes, gray hair develops, as melanosomes differentiate but fail to grow, resulting in organelle miniaturization. We conclude that Bmpr2 and Acvr2a normally play cell-type-specific, necessary roles in organelle biogenesis and the shutdown of developmental programs and cell division. PMID:22611050

  16. Dimethyl sulfoxide (DMSO) exacerbates cisplatin-induced sensory hair cell death in zebrafish (Danio rerio).

    PubMed

    Uribe, Phillip M; Mueller, Melissa A; Gleichman, Julia S; Kramer, Matthew D; Wang, Qi; Sibrian-Vazquez, Martha; Strongin, Robert M; Steyger, Peter S; Cotanche, Douglas A; 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 the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO.

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

    PubMed Central

    Gleichman, Julia S.; Kramer, Matthew D.; Wang, Qi; Sibrian-Vazquez, Martha; Strongin, Robert M.; Steyger, Peter S.; Cotanche, Douglas A.; 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 the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells in the presence of ototoxic drugs. Dimethyl sulfoxide (DMSO) is typically used as a solvent for many pharmacological agents in sensory hair cell cytotoxicity assays. Serendipitously, we found that DMSO potentiated the effects of cisplatin and killed more sensory hair cells than treatment with cisplatin alone. Yet, DMSO alone did not kill hair cells. We did not observe the synergistic effects of DMSO with the ototoxic aminoglycoside antibiotic neomycin. Cisplatin treatment with other commonly used organic solvents (i.e. ethanol, methanol, and polyethylene glycol 400) also did not result in increased cell death compared to cisplatin treatment alone. Thus, caution should be exercised when interpreting data generated from small molecule screens since many compounds are dissolved in DMSO. PMID:23383324

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

    PubMed Central

    Leirós, Gustavo José; Kusinsky, Ana Gabriela; Drago, Hugo; Bossi, Silvia; Sturla, Flavio; Castellanos, María Lía; Stella, Inés Yolanda

    2014-01-01

    Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair. PMID:25161315

  20. Towards a Molecular Understanding of Noise-Induced Hearing Loss

    DTIC Science & Technology

    2016-10-01

    gene expression following different types of noise exposure and their treatments, in the inner ear. To this end, we have (a) Established the hair ...in hair cells, support cells and whole inner ears, 6 and 24 hours after noise exposure; (c) Collected and processed most of the tissue for TTS...SUBJECT TERMS Permanent threshold shift, Temporary threshold shift, Noise induced hearing loss, Ribotag, RNA-seq, hair cell, supporting cell, SAHA

  1. Normal and aging hair biology and structure 'aging and hair'.

    PubMed

    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. © 2015 S. Karger AG, Basel.

  2. Proteomic Analysis of Hair Follicles

    NASA Astrophysics Data System (ADS)

    Ishioka, Noriaki; Terada, Masahiro; Yamada, Shin; Seki, Masaya; Takahashi, Rika; Majima, Hideyuki J.; Higashibata, Akira; Mukai, Chiaki

    2013-02-01

    Hair root cells actively divide in a hair follicle, and they sensitively reflect physical conditions. By analyzing the human hair, we can know stress levels on the human body and metabolic conditions caused by microgravity environment and cosmic radiation. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. During long-term flights, the physiological effects on astronauts include muscle atrophy and bone calcium loss. Furthermore, radiation and psychological effects are important issue to consider. Therefore, an understanding of the effects of the space environment is important for developing countermeasures against the effects experienced by astronauts. In this experiment, we identify functionally important target proteins that integrate transcriptome, mineral metabolism and proteome profiles from human hair. To compare the protein expression data with the gene expression data from hair roots, we developed the protein processing method. We extracted the protein from five strands of hair using ISOGEN reagents. Then, these extracted proteins were analyzed by LC-MS/MS. These collected profiles will give us useful physiological information to examine the effect of space flight.

  3. microRNA-183 is Essential for Hair Cell Regeneration after Neomycin Injury in Zebrafish.

    PubMed

    Kim, Chang Woo; Han, Ji Hyuk; Wu, Ling; Choi, Jae Young

    2018-01-01

    microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. In the present study, we show that the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and that its inhibition reduces hair cell regeneration following neomycin-induced ototoxicity in zebrafish. miRNA expression patterns after neomycin exposure were analyzed using microarray chips. Quantitative polymerase chain reaction was performed to validate miR-183 cluster expression patterns following neomycin exposure (500 μM for 2 h). After injection of an antisense morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell regeneration after neomycin exposure in neuromast cells was evaluated by fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair cells. Microarray analysis clearly showed that the miR-183 cluster (miR-96, miR-182, and miR-183) was upregulated after neomycin treatment. We also confirmed upregulated expression of the miR-183 cluster during hair cell regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183 reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish larvae. Our work demonstrates that the miR-183 cluster is essential for the regeneration of hair cells following ototoxic injury in zebrafish larvae. Therefore, regulation of the miR-183 cluster can be a novel target for stimulation of hair cell regeneration. © Copyright: Yonsei University College of Medicine 2018

  4. Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo

    NASA Technical Reports Server (NTRS)

    Matsui, Jonathan I.; Haque, Asim; Huss, David; Messana, Elizabeth P.; Alosi, Julie A.; Roberson, David W.; Cotanche, Douglas A.; Dickman, J. David; Warchol, Mark E.

    2003-01-01

    The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

  5. [Status of scalp hair and therapy of alopecia in men in Switzerland].

    PubMed

    Trüeb, R M; de Viragh, P A

    2001-02-15

    A community-based interview and a questionnaire of men visiting the dermatologist for treatment of hair loss were conducted in Switzerland, to characterize the significance of scalp hair and self-perception of hair loss in Swiss men, and to evaluate current treatment of hair loss. 508 men, aged 15-74 years, regardless of the degree of hair loss, were interviewed by telephone, and 308 patient questionnaires were completed by 19 dermatologists. The questions addressed by the interview were: degree of self-rated hair loss, time invested for hair care, use or reasons for rejecting hair growing agents, relevant criteria for scalp hair, self-assessment with respect to different "hair communication types". The questionnaire analysed the causes of hair loss, prior and current treatment modalities, and follow-up at the dermatologist. Respondents rated their hair loss on a 5-point, textual scale that ranged from 'no hair loss' to 'bald areas'. 43% reported hair loss to some extent. For 42% a full head of hair was very important, especially for men under 29 years, who invested more time for hair care and had not lost hair. Of men with hair loss, 26% previously applied hair growing agents. Of men consulting the dermatologist for hair loss, 90% had androgenetic alopecia. 37% were previously treated: prior treatment was in 59% minoxidil, in 4% finasteride (Propecia), in 7% Aminexil, in 7% dietary supplements, and in 6% conducted by the hair dresser. In 79% treatment was switched to Propecia: of these, 73% adhered to the follow-up consultations at the dermatologist.

  6. Artificial hair cell integrated with an artificial neuron: Interplay between criticality and excitability

    NASA Astrophysics Data System (ADS)

    Lee, Woo Seok; Jeong, Wonhee; Ahn, Kang-Hun

    2014-12-01

    We provide a simple dynamical model of a hair cell with an afferent neuron where the spectral and the temporal responses are controlled by the hair bundle's criticality and the neuron's excitability. To demonstrate that these parameters, indeed, specify the resolution of the sound encoding, we fabricate a neuromorphic device that models the hair cell bundle and its afferent neuron. Then, we show that the neural response of the biomimetic system encodes sounds with either high temporal or spectral resolution or with a combination of both resolutions. Our results suggest that the hair cells may easily specialize to fulfil various roles in spite of their similar physiological structures.

  7. Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

    PubMed

    Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

    2017-09-01

    Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21 CIP1 , p27 KIP1 and p57 KIP2 ) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21 CIP1 , p27 KIP1 and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57 KIP2 protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

  8. Fullerene nanomaterials potentiate hair growth.

    PubMed

    Zhou, Zhiguo; Lenk, Robert; Dellinger, Anthony; MacFarland, Darren; Kumar, Krishan; Wilson, Stephen R; Kepley, Christopher L

    2009-06-01

    Hair loss is a common symptom resulting from a wide range of disease processes and can lead to stress in affected individuals. The purpose of this study was to examine the effect of fullerene nanomaterials on hair growth. We used shaved mice as well as SKH-1 "bald" mice to determine if fullerene-based compounds could affect hair growth and hair follicle numbers. In shaved mice, fullerenes increase the rate of hair growth as compared with mice receiving vehicle only. In SKH-1 hairless mice fullerene derivatives given topically or subdermally markedly increased hair growth. This was paralleled by a significant increase in the number of hair follicles in fullerene-treated mice as compared with those mice treated with vehicle only. The fullerenes also increased hair growth in human skin sections maintained in culture. These studies have wide-ranging implications for those conditions leading to hair loss, including alopecia, chemotherapy, and reactions to various chemicals.

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

    NASA Astrophysics Data System (ADS)

    McEwan, Alistair; van Schaik, André

    2003-12-01

    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.

  10. Ion flow in cochlear hair cells and the regulation of hearing sensitivity.

    PubMed

    Patuzzi, Robert

    2011-10-01

    This paper discusses how ion transport proteins in the hair cells of the mammalian cochlea work to produce a sensitive but stable hearing organ. The transport proteins in the inner and outer hair cells are summarized (including their current voltage characteristics), and the roles of these proteins in determining intracellular Ca(2+), membrane potential, and ultimately cochlear sensitivity are discussed. The paper also discusses the role of the Ca(2+) sequestration sacs in outer hair cells in the autoregulation of hair cell membrane potential and cochlear gain, and how the underdamped control of Ca(2+) within these sacs may produce the observed slow oscillations in cochlear sensitivity and otoacoustic emissions after cochlear perturbations, including perilymphatic perfusions and prolonged low-frequency tones. The relative insensitivity of cochlear gain to short-term changes in the endocochlear potential is also discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Why care about linear hair growth rates (LHGR)? a study using in vivo imaging and computer assisted image analysis after manual processing (CAIAMP) in unaffected male controls and men with male pattern hair loss (MPHL).

    PubMed

    Van Neste, Dominique

    2014-01-01

    The words "hair growth" frequently encompass many aspects other than just growth. Report on a validation method for precise non-invasive measurement of thickness together with linear hair growth rates of individual hair fibres. To verify the possible correlation between thickness and linear growth rate of scalp hair in male pattern hair loss as compared with healthy male controls. To document the process of validation of hair growth measurement from in vivo image capturing and manual processing, followed by computer assisted image analysis. We analysed 179 paired images obtained with the contrast-enhanced-phototrichogram method with exogen collection (CE-PTG-EC) in 13 healthy male controls and in 87 men with male pattern hair loss (MPHL). There was a global positive correlation between thickness and growth rate (ANOVA; p<0.0001) and a statistically significantly (ANOVA; p<0.0005) slower growth rate in MPHL as compared with equally thick hairs from controls. Finally, the growth rate recorded in the more severe patterns was significantly (ANOVA; P ≤ 0.001) reduced compared with equally thick hair from less severely affected MPHL or controls subjects. Reduced growth rate, together with thinning and shortening of the anagen phase duration in MPHL might contribute together to the global impression of decreased hair volume on the top of the head. Amongst other structural and functional parameters characterizing hair follicle regression, linear hair growth rate warrants further investigation, as it may be relevant in terms of self-perception of hair coverage, quantitative diagnosis and prognostic factor of the therapeutic response.

  12. Characteristics of MIC-1 antlerogenic stem cells and their effect on hair growth in rabbits.

    PubMed

    Cegielski, Marek; Izykowska, Ilona; Chmielewska, Magdalena; Dziewiszek, Wojciech; Bochnia, Marek; Calkosinski, Ireneusz; Dziegiel, Piotr

    2013-01-01

    We characterized growth factors produced by MIC-1 antlerogenic stem cells and attempted to apply those cells to stimulate hair growth in rabbits. We evaluated the gene and protein expression of growth factors by immunocytochemical and molecular biology techniques in MIC-1 cells. An animal model was used to assess the effects of xenogenous stem cells on hair growth. In the experimental group, rabbits were intradermally injected with MIC-1 stem cells, whereas the control group rabbits were given vehicle-only. After 1, 2 and 4 weeks, skin specimen were collected for histological and immunohistochemical tests. MIC-1 antlerogenic stem cells express growth factors, as confirmed at the mRNA and protein levels. Histological and immunohistochemical analysis demonstrated an increase in the number of hair follicles, as well as the amount of secondary hair in the follicles, without an immune response in animals injected intradermally with MIC-1 cells, compared to animals receiving vehicle-alone. MIC-1 cells accelerated hair growth in rabbits due to the activation of cells responsible for the regulation of the hair growth cycle through growth factors. Additionally, the xenogenous cell implant did not induce immune response.

  13. Progressive Hearing Loss in Mice Carrying a Mutation in Usp53

    PubMed Central

    Kazmierczak, Marcin; Harris, Suzan L.; Kazmierczak, Piotr; Shah, Prahar; Starovoytov, Valentin; Ohlemiller, Kevin K.

    2015-01-01

    Disordered protein ubiquitination has been linked to neurodegenerative disease, yet its role in inner ear homeostasis and hearing loss is essentially unknown. Here we show that progressive hearing loss in the ethylnitrosourea-generated mambo mouse line is caused by a mutation in Usp53, a member of the deubiquitinating enzyme family. USP53 contains a catalytically inactive ubiquitin-specific protease domain and is expressed in cochlear hair cells and a subset of supporting cells. Although hair cell differentiation is unaffected in mambo mice, outer hair cells degenerate rapidly after the first postnatal week. USP53 colocalizes and interacts with the tight junction scaffolding proteins TJP1 and TJP2 in polarized epithelial cells, suggesting that USP53 is part of the tight junction complex. The barrier properties of tight junctions of the stria vascularis appeared intact in a biotin tracer assay, but the endocochlear potential is reduced in adult mambo mice. Hair cell degeneration in mambo mice precedes endocochlear potential decline and is rescued in cochlear organotypic cultures in low potassium milieu, indicating that hair cell loss is triggered by extracellular factors. Remarkably, heterozygous mambo mice show increased susceptibility to noise injury at high frequencies. We conclude that USP53 is a novel tight junction-associated protein that is essential for the survival of auditory hair cells and normal hearing in mice, possibly by modulating the barrier properties and mechanical stability of tight junctions. SIGNIFICANCE STATEMENT Hereditary hearing loss is extremely prevalent in the human population, but many genes linked to hearing loss remain to be discovered. Forward genetics screens in mice have facilitated the identification of genes involved in sensory perception and provided valuable animal models for hearing loss in humans. This involves introducing random mutations in mice, screening the mice for hearing defects, and mapping the causative mutation

  14. A two-step mechanism for stem cell activation during hair regeneration.

    PubMed

    Greco, Valentina; Chen, Ting; Rendl, Michael; Schober, Markus; Pasolli, H Amalia; Stokes, Nicole; Dela Cruz-Racelis, June; Fuchs, Elaine

    2009-02-06

    Hair follicles (HFs) undergo cyclic bouts of degeneration, rest, and regeneration. During rest (telogen), the hair germ (HG) appears as a small cell cluster between the slow-cycling bulge and dermal papilla (DP). Here we show that HG cells are derived from bulge stem cells (SCs) but become responsive quicker to DP-promoting signals. In vitro, HG cells also proliferate sooner but display shorter-lived potential than bulge cells. Molecularly, they more closely resemble activated bulge rather than transit-amplifying (matrix) cells. Transcriptional profiling reveals precocious activity of both HG and DP in late telogen, accompanied by Wnt signaling in HG and elevated FGFs and BMP inhibitors in DP. FGFs and BMP inhibitors participate with Wnts in exerting selective and potent stimuli to the HG both in vivo and in vitro. Our findings suggest a model where HG cells fuel initial steps in hair regeneration, while the bulge is the engine maintaining the process.

  15. A role for CSLD3 during cell-wall synthesis in apical plasma membranes of tip-growing root-hair cells.

    PubMed

    Park, Sungjin; Szumlanski, Amy L; Gu, Fangwei; Guo, Feng; Nielsen, Erik

    2011-07-17

    In plants, cell shape is defined by the cell wall, and changes in cell shape and size are dictated by modification of existing cell walls and deposition of newly synthesized cell-wall material. In root hairs, expansion occurs by a process called tip growth, which is shared by root hairs, pollen tubes and fungal hyphae. We show that cellulose-like polysaccharides are present in root-hair tips, and de novo synthesis of these polysaccharides is required for tip growth. We also find that eYFP-CSLD3 proteins, but not CESA cellulose synthases, localize to a polarized plasma-membrane domain in root hairs. Using biochemical methods and genetic complementation of a csld3 mutant with a chimaeric CSLD3 protein containing a CESA6 catalytic domain, we provide evidence that CSLD3 represents a distinct (1→4)-β-glucan synthase activity in apical plasma membranes during tip growth in root-hair cells.

  16. P2X antagonists inhibit styryl dye entry into hair cells.

    PubMed

    Crumling, M A; Tong, M; Aschenbach, K L; Liu, L Qian; Pipitone, C M; Duncan, R K

    2009-07-21

    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 intracellular fluorescence that is often used as a molecular indication of mechanotransduction channel activity. However, such dyes can also permeate the ATP receptor, P2X(2). Therefore, we explored the contribution of P2X receptors to the loading of hair cells with AM1-43. The chick inner ear was found to express P2X receptors and to release ATP, similar to the inner ear of mammals, allowing for the endogenous stimulation of P2X receptors. The involvement of these receptors was evaluated pharmacologically, by exposing the sensory epithelium of the chick inner ear to 5 microM AM1-43 under different experimental conditions and measuring the fluorescence in hair cells after fixation of the tissue. Pre-exposure of the tissue to 5 mM EGTA for 15 min, which should eliminate most of the gating "tip links" of the mechanotransduction channels, deceased fluorescence by only 44%. In contrast, P2X receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid [PPADS], suramin, 2',3'-O-(2,4,6-trinitrophenyl) ATP [TNP-ATP], and d-tubocurarine) had greater effects on dye loading. PPADS, suramin, and TNP-ATP all decreased intracellular AM1-43 fluorescence in hair cells by at least 69% when applied at a concentration of 100 microM. The difference between d-tubocurarine-treated and control fluorescence was statistically insignificant when d-tubocurarine was applied at a concentration that blocks the mechanotransduction channel (200 microM). At a concentration that also blocks P2X(2) receptors (2 mM), d-tubocurarine decreased dye loading by 72%. From these experiments, it appears that AM1-43 can enter hair cells through endogenously activated P2X receptors. Thus, the contribution of P2X

  17. ROOT HAIR DEFECTIVE SIX-LIKE4 (RSL4) promotes root hair elongation by transcriptionally regulating the expression of genes required for cell growth.

    PubMed

    Vijayakumar, Priya; Datta, Sourav; Dolan, Liam

    2016-12-01

    ROOT HAIR DEFECTIVE SIX-LIKE4 (RSL4) is necessary and sufficient for root hair elongation in Arabidopsis thaliana. Root hair length is determined by the duration for which RSL4 protein is present in the developing root hair. The aim of this research was to identify genes regulated by RSL4 that affect root hair growth. To identify genes regulated by RSL4, we identified genes whose expression was elevated by induction of RSL4 activity in the presence of an inhibitor of translation. Thirty-four genes were identified as putative targets of RSL transcriptional regulation, and the results suggest that the activities of SUPPRESSOR OF ACTIN (SAC1), EXOCSYT SUBUNIT 70A1 (EXO70A1), PEROXIDASE7 (PRX7) and CALCIUM-DEPENDENT PROTEIN KINASE11 (CPK11) are required for root hair elongation. These data indicate that RSL4 controls cell growth by controlling the expression of genes encoding proteins involved in cell signalling, cell wall modification and secretion. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  18. Numerical simulation of the hair formation -modeling of hair cycle

    NASA Astrophysics Data System (ADS)

    Kajihara, Narumichi; Nagayama, Katsuya

    2018-01-01

    In the recent years, the fields of study of anti-aging, health and beauty, cosmetics, and hair diseases have attracted significant attention. In particular, human hair is considered to be an important aspect with regard to an attractive appearance. To this end, many workers have sought to understand the formation mechanism of the hair root. However, observing growth in the hair root is difficult, and a detailed mechanism of the process has not yet been elucidated. Hair repeats growth, retraction, and pause cycles (hair cycle) in a repetitive process. In the growth phase, hair is formed through processes of cell proliferation and differentiation (keratinization). During the retraction phase, hair growth stops, and during the resting period, hair fall occurs and new hair grows. This hair cycle is believed to affect the elongation rate, thickness, strength, and shape of hair. Therefore, in this study, we introduce a particle model as a new method to elucidate the unknown process of hair formation, and to model the hair formation process accompanying the proliferation and differentiation of the hair root cells in all three dimensions. In addition, to the growth period, the retraction and the resting periods are introduced to realize the hair cycle using this model.

  19. 1α,25-dihydroxyvitamin D3 modulates the hair-inductive capacity of dermal papilla cells: therapeutic potential for hair regeneration.

    PubMed

    Aoi, Noriyuki; Inoue, Keita; Chikanishi, Toshihiro; Fujiki, Ryoji; Yamamoto, Hanako; Kato, Harunosuke; Eto, Hitomi; Doi, Kentaro; Itami, Satoshi; Kato, Shigeaki; Yoshimura, Kotaro

    2012-08-01

    Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell-based hair regrowth therapy. We previously reported that 1α,25-dihydroxyvitamin D(3) (VD(3)) upregulates expression of transforming growth factor (TGF)-β2 and alkaline phosphatase (ALP) activity, both features of hair-inducing human DPCs (hDPCs). In this study, we further examined the effects and signaling pathways associated with VD(3) actions on DPCs. VD(3) suppressed hDPC proliferation in a dose-dependent, noncytotoxic manner. Among the Wnt-related genes investigated, Wnt10b expression was significantly upregulated by VD(3) in hDPCs. Wnt10b upregulation, as well as upregulation of ALPL (ALP, liver/bone/kidney) and TGF-β2, by VD(3) was specific in hDPCs and not detected in human dermal fibroblasts. Screening of paracrine or endocrine factors in the skin indicated that all-trans retinoic acid (atRA) upregulated Wnt10b gene expression, although synergistic upregulation (combined atRA and VD(3)) was not seen. RNA interference with vitamin D receptor (VDR) revealed that VD(3) upregulation of Wnt10b, ALPL, and TGF-β2 was mediated through the genomic VDR pathway. In a rat model of de novo hair regeneration by murine DPC transplantation, pretreatment with VD(3) significantly enhanced hair folliculogenesis. Specifically, a greater number of outgrowing hair shafts and higher maturation of regenerated follicles were observed. Together, these data suggest that VD(3) may promote functional differentiation of DPCs and be useful in preserving the hair follicle-inductive capacity of cultured DPCs for hair regeneration therapies.

  20. 1α,25-Dihydroxyvitamin D3 Modulates the Hair-Inductive Capacity of Dermal Papilla Cells: Therapeutic Potential for Hair Regeneration

    PubMed Central

    Aoi, Noriyuki; Inoue, Keita; Chikanishi, Toshihiro; Fujiki, Ryoji; Yamamoto, Hanako; Kato, Harunosuke; Eto, Hitomi; Doi, Kentaro; Itami, Satoshi; Kato, Shigeaki

    2012-01-01

    Dermal papilla cells (DPCs) have the potential to induce differentiation of epithelial stem cells into hair, and Wnt signaling is deeply involved in the initiation process. The functional limitation of expanded adult DPCs has been a difficult challenge for cell-based hair regrowth therapy. We previously reported that 1α,25-dihydroxyvitamin D3 (VD3) upregulates expression of transforming growth factor (TGF)-β2 and alkaline phosphatase (ALP) activity, both features of hair-inducing human DPCs (hDPCs). In this study, we further examined the effects and signaling pathways associated with VD3 actions on DPCs. VD3 suppressed hDPC proliferation in a dose-dependent, noncytotoxic manner. Among the Wnt-related genes investigated, Wnt10b expression was significantly upregulated by VD3 in hDPCs. Wnt10b upregulation, as well as upregulation of ALPL (ALP, liver/bone/kidney) and TGF-β2, by VD3 was specific in hDPCs and not detected in human dermal fibroblasts. Screening of paracrine or endocrine factors in the skin indicated that all-trans retinoic acid (atRA) upregulated Wnt10b gene expression, although synergistic upregulation (combined atRA and VD3) was not seen. RNA interference with vitamin D receptor (VDR) revealed that VD3 upregulation of Wnt10b, ALPL, and TGF-β2 was mediated through the genomic VDR pathway. In a rat model of de novo hair regeneration by murine DPC transplantation, pretreatment with VD3 significantly enhanced hair folliculogenesis. Specifically, a greater number of outgrowing hair shafts and higher maturation of regenerated follicles were observed. Together, these data suggest that VD3 may promote functional differentiation of DPCs and be useful in preserving the hair follicle-inductive capacity of cultured DPCs for hair regeneration therapies. PMID:23197867

  1. Hair transplantation in burn scar alopecia

    PubMed Central

    Farjo, Bessam; Farjo, Nilofer; Williams, Greg

    2015-01-01

    Treating patients with burn alopecia or hair loss can often be a challenge to both the surgeon and the patient. As with other reconstructive procedures that are required in the post-burn phase, this is usually a multiple stage process often requiring surgery over several years. This is because graft take is not as reliable as in healthy non-scarred skin and may need repeating to achieve adequate density. Also, different areas of hair loss may need to be addressed in separate procedures. There are several limiting factors that will determine whether or not a patient is a candidate for hair restoration which includes but is not limited to the amount of hair loss and the availability of suitable donor hair. Here we discuss how the current surgical technique of hair transplant surgery by follicular unit extraction (FUE) or strip follicular unit transplant (FUT) has become the treatment of choice for alopecic areas that require a more refined aesthetic result. Eyebrow, eyelash, beard and scalp hair loss can all have a negative impact on a burn survivor’s self-esteem and even if surgery is not a possibility, there are non-surgical options available for hair restoration and these are also discussed. PMID:29799573

  2. Falsification of the ionic channel theory of hair cell transduction.

    PubMed

    Rossetto, Michelangelo

    2013-11-01

    The hair cell provides the transduction of mechanical vibrations in the balance and acoustic sense of all vertebrates that swim, walk, or fly. The current theory places hair cell transduction in a mechanically controlled ion channel. Although the theory of a mechanical input modulating the flow of ions through an ion pore has been a useful tool, it is falsified by experimental data in the literature and can be definitively falsified by a proposed experiment.

  3. Caprin-1 is a target of the deafness gene Pou4f3 and is recruited to stress granules in cochlear hair cells in response to ototoxic damage

    PubMed Central

    Towers, Emily R.; Kelly, John J.; Sud, Richa; Gale, Jonathan E.; Dawson, Sally J.

    2011-01-01

    The POU4 family of transcription factors are required for survival of specific cell types in different sensory systems. Pou4f3 is essential for the survival of auditory sensory hair cells and several mutations in human POU4F3 cause hearing loss. Thus, genes regulated by Pou4f3 are likely to be essential for hair cell survival. We performed a subtractive hybridisation screen in an inner-ear-derived cell line to find genes with differential expression in response to changes in Pou4f3 levels. The screen identified the stress-granule-associated protein Caprin-1 as being downregulated by Pou4f3. We demonstrated that this regulation occurs through the direct interaction of Pou4f3 with binding sites in the Caprin-1 5′ flanking sequence, and describe the expression pattern of Caprin-1 mRNA and protein in the cochlea. Moreover, we found Caprin-1-containing stress granules are induced in cochlear hair cells following aminoglycoside-induced damage. This is the first report of stress granule formation in mammalian hair cells and suggests that the formation of Caprin-1-containing stress granules is a key damage response to a clinically relevant ototoxic agent. Our results have implications for the understanding of aminoglycoside-induced hearing loss and provide further evidence that stress granule formation is a fundamental cellular stress response. PMID:21402877

  4. Guidelines for the diagnosis and treatment of male-pattern and female-pattern hair loss, 2017 version.

    PubMed

    Manabe, Motomu; Tsuboi, Ryoji; Itami, Satoshi; Osada, Shin-Ichi; Amoh, Yasuyuki; Ito, Taisuke; Inui, Shigeki; Ueki, Rie; Ohyama, Manabu; Kurata, Sotaro; Kono, Takeshi; Saito, Norimitsu; Sato, Akio; Shimomura, Yutaka; Nakamura, Motonobu; Narusawa, Hiroshi; Yamazaki, Masashi

    2018-06-04

    Male-pattern hair loss (MPHL, androgenetic alopecia) is a slowly progressive form of alopecia which begins after puberty. In 2010, we published the first Japanese edition of guidelines for the diagnosis and treatment of MPHL. It achieved the original goal of providing physicians and patients in Japan with evidence-based information for choosing efficacious and safe therapy for MPHL. Subsequently, new therapeutic drugs and treatment methods have been developed, and women's perception of MPHL has undergone change and the term "female-pattern hair loss (FPHL)" is becoming more common internationally. Thus, here we report a revised version of the 2010 guidelines aimed at both MPHL and FPHL. In these guidelines, finasteride 1 mg daily, dutasteride 0.5 mg daily and topical 5% minoxidil twice daily for MPHL, and topical 1% minoxidil twice daily for FPHL, are recommended as the first-line treatments. Self-hair transplantation, irradiation by light-emitting diodes and low-level lasers, and topical application of adenosine for MPHL are recommended, whereas prosthetic hair transplantation and oral administration of minoxidil should not be performed. Oral administration of finasteride or dutasteride are contraindicated for FPHL. In addition, we have evaluated the effectiveness of topical application of carpronium chloride, t-flavanone, cytopurine, pentadecane and ketoconazole, and wearing a wig. Unapproved topical application of bimatoprost and latanoprost, and emerging hair regeneration treatments have also been addressed. We believe that the revised guidelines will improve further the diagnostic and treatment standards for MPHL add FPHL in Japan. © 2018 Japanese Dermatological Association.

  5. Synaptic hyperpolarization and inhibition of turtle cochlear hair cells.

    PubMed

    Art, J J; Fettiplace, R; Fuchs, P A

    1984-11-01

    Intracellular recordings were made from turtle cochlear hair cells in order to examine the properties of the post-synaptic potentials evoked by electrical stimulation of the efferent axons. Single shocks to the efferents generated a hair cell membrane hyperpolarization with an average amplitude generally less than 1 mV and lasting for about 100 ms. With short trains of shocks, the size of the post-synaptic potential grew markedly to a maximum of 20-30 mV. The interaction between pairs of shocks separated by a varying interval was studied. For an interval of 4 ms, the response to the second shock was increased on average by a factor of 3 and the conditioning effect of the first shock decayed with a time constant of about 100 ms. We suggest the augmentation in response to trains of shocks may be partly due to facilitation of efferent transmitter release. The efferent post-synaptic potentials could be reversibly abolished by perfusion with perilymphs containing 3 microM-curare or atropine, and infusion of acetylcholine gave a transient membrane hyperpolarization. These observations are consistent with efferent action being mediated via a cholinergic synapse onto the hair cells. The post-synaptic potentials could be reversed in polarity by injection of hyperpolarizing currents through the recording electrode. The reversal potential was estimated as about -80 mV, 30 mV negative to the resting potential. Near reversal, a small brief depolarization was evident and may constitute a minor component of the synaptic response. The value of the reversal potential was unaffected by substitution of the perilymphatic chloride, but was altered in a predictable manner by changes in extracellular potassium concentration indicating that the post-synaptic potentials arise mainly by an increase in the permeability of the hair cell membrane to potassium ions. Throughout the post-synaptic hyperpolarization there was a reduction in the sensitivity of the hair cell to tones at its

  6. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties

    PubMed Central

    Rendl, Michael; Polak, Lisa; Fuchs, Elaine

    2008-01-01

    Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor 1a in purified DP cells. When DPs cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial–mesenchymal cross-talk necessary to make hair. PMID:18281466

  7. Establishment of human hair follicle mesenchymal stem cells with overexpressed human hepatocyte growth factor.

    PubMed

    Zhou, Dan; Cheng, Hongjing; Liu, Jinyu; Zhang, Lei

    2017-06-01

    Chronic liver disease has become a major health problem that causes serious damage to human health. Since the existing treatment effect was not ideal, we need to seek new treatment methods. We utilized the gene recombination technology to obtain the human hair mesenchymal stem cells which overexpression of human hepatocyte growth factor (hHGF). Furthermore, we verified the property of transfected cells through detecting surface marker by flow cytometry. We show here establishment of the hHGF-overexpressing lentivirus vector, and successfully transfection to human hair follicle mesenchymal stem cells. The verified experiments could demonstrate the human hair follicle mesenchymal stem cells which have been transfected still have the properties of stem cells. We successfully constructed human hair follicle mesenchymal stem cells which overexpression hHGF, and maintain the same properties compared with pro-transfected cells.

  8. Curing Hearing Loss: Patient Expectations, Health Care Practitioners, and Basic Science

    ERIC Educational Resources Information Center

    Oshima, Kazuo; Suchert, Steffen; Blevins, Nikolas H.; Heller, Stefan

    2010-01-01

    Millions of patients are debilitated by hearing loss, mainly caused by degeneration of sensory hair cells in the cochlea. The underlying reasons for hair cell loss are highly diverse, ranging from genetic disposition, drug side effects, traumatic noise exposure, to the effects of aging. Whereas modern hearing aids offer some relief of the symptoms…

  9. Promotion of anagen, increased hair density and reduction of hair fall in a clinical setting following identification of FGF5-inhibiting compounds via a novel 2-stage process

    PubMed Central

    Burg, Dominic; Yamamoto, Masakuni; Namekata, Masato; Haklani, Joseph; Koike, Koichiro; Halasz, Maria

    2017-01-01

    Background There are very few effective, scientifically validated treatments with known mechanisms of action for treatment of hair loss in both men and women. Fibroblast growth factor 5 (FGF5) is an important factor in the irreversible transition from anagen to catagen, and inhibition of FGF5 prolongs anagen phase and reduces hair loss. Objective We aimed to screen botanically derived molecules for FGF5 inhibitory activity in vitro and assess efficacy in a clinical setting. Methods We screened for FGF5 inhibitory efficacy via a novel 2-step in vitro pipeline consisting of an engineered FGF5 responsive cell line, followed by an activated dermal papillae (DP) cell method. Efficacy in a clinical setting was assessed in a randomized, single-blind, placebo-controlled trial against early- to mid-stage pattern hair loss in men and women. Results We observed FGF5 inhibitory activity for a number of compounds from the monoterpenoid family, many showing greater inhibitory efficacy than our previously reported crude plant extracts. Evaluation of a lead candidate in a clinical study over 112 days showed a significant improvement in anagen:telogen (AT) ratio (p = 0.002), reduced hair fall (p = 0.007) and improved visual grading (p = 0.004). Scientifically matched photography on a subgroup of randomly chosen participants highlighted significant improvement in hair density, with increases evident in all tested participants compared to baseline. Conclusion Isolates from the monoterpenoid family displayed efficacy in FGF5 inhibition in vitro. A topical formulation containing a leading isolate significantly improved AT ratio, reduced hair fall and increased apparent hair density in the tested population of men and women. PMID:28280377

  10. Hair Transplantation Controversies.

    PubMed

    Avram, Marc R; Finney, Robert; Rogers, Nicole

    2017-11-01

    Hair transplant surgery creates consistently natural appearing transplanted hair for men. It is increasingly popular procedure to restore natural growing hair for men with hair loss. To review some current controversies in hair transplant surgery. Review of the English PubMed literature and specialty literature in hair transplant surgery. Some of the controversies in hair transplant surgery include appropriate donor harvesting technique including elliptical donor harvesting versus follicular unit extraction whether manual versus robotic, the role of platelet-rich plasma and low-level light surgery in hair transplant surgery. Hair transplant surgery creates consistently natural appearing hair. As with all techniques, there are controversies regarding the optimal method for performing the procedure. Some of the current controversies in hair transplant surgery include optimal donor harvesting techniques, elliptical donor harvesting versus follicular unit extraction, the role of low-level light therapy and the platelet-rich plasma therapy in the procedure. Future studies will further clarify their role in the procedure.

  11. Changes in ribbon synapses and rough endoplasmic reticulum of rat utricular macular hair cells in weightlessness

    NASA Technical Reports Server (NTRS)

    Ross, M. D.

    2000-01-01

    This study combined ultrastructural and statistical methods to learn the effects of weightlessness on rat utricular maculae. A principle aim was to determine whether weightlessness chiefly affects ribbon synapses of type II cells, since the cells communicate predominantly with branches of primary vestibular afferent endings. Maculae were microdissected from flight and ground control rat inner ears collected on day 13 of a 14-day spaceflight (F13), landing day (R0) and day 14 postflight (R14) and were prepared for ultrastructural study. Ribbon synapses were counted in hair cells examined in a Zeiss 902 transmission electron microscope. Significance of synaptic mean differences was determined for all hair cells contained within 100 section series, and for a subset of complete hair cells, using SuperANOVA software. The synaptic mean for all type II hair cells of F13 flight rats increased by 100%, and that for complete cells by 200%. Type I cells were less affected, with synaptic mean differences statistically insignificant in complete cells. Synapse deletion began within 8 h upon return to Earth. Additionally, hair cell laminated rough endoplasmic reticulum of flight rats was reversibly disorganized on R0. Results support the thesis that synapses in type II hair cells are uniquely affected by altered gravity. Type II hair cells may be chiefly sensors of gravitational and type I cells of translational linear accelerations.

  12. Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells

    PubMed Central

    Takeda, Norifumi; Jain, Rajan; LeBoeuf, Matthew R.; Padmanabhan, Arun; Wang, Qiaohong; Li, Li; Lu, Min Min; Millar, Sarah E.; Epstein, Jonathan A.

    2013-01-01

    The mammalian hair follicle relies on adult resident stem cells and their progeny to fuel and maintain hair growth throughout the life of an organism. The cyclical and initially synchronous nature of hair growth makes the hair follicle an ideal system with which to define homeostatic mechanisms of an adult stem cell population. Recently, we demonstrated that Hopx is a specific marker of intestinal stem cells. Here, we show that Hopx specifically labels long-lived hair follicle stem cells residing in the telogen basal bulge. Hopx+ cells contribute to all lineages of the mature hair follicle and to the interfollicular epidermis upon epidermal wounding. Unexpectedly, our analysis identifies a previously unappreciated progenitor population that resides in the lower hair bulb of anagen-phase follicles and expresses Hopx. These cells co-express Lgr5, do not express Shh and escape catagen-induced apoptosis. They ultimately differentiate into the cytokeratin 6-positive (K6) inner bulge cells in telogen, which regulate the quiescence of adjacent hair follicle stem cells. Although previous studies have suggested that K6+ cells arise from Lgr5-expressing lower outer root sheath cells in anagen, our studies indicate an alternative origin, and a novel role for Hopx-expressing lower hair bulb progenitor cells in contributing to stem cell homeostasis. PMID:23487314

  13. Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells

    PubMed Central

    Veraitch, Ophelia; Mabuchi, Yo; Matsuzaki, Yumi; Sasaki, Takashi; Okuno, Hironobu; Tsukashima, Aki; Amagai, Masayuki; Okano, Hideyuki; Ohyama, Manabu

    2017-01-01

    The dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties. The resultant cells (induced DP-substituting cells [iDPSCs]) exhibited up-regulated DP markers, interacted with human keratinocytes to up-regulate HF related genes, and when co-grafted with human keratinocytes in vivo gave rise to fibre structures with a hair cuticle-like coat resembling the hair shaft, as confirmed by scanning electron microscope analysis. Furthermore, iDPSCs responded to the clinically used hair growth reagent, minoxidil sulfate, to up-regulate DP genes, further supporting that they were capable of, at least in part, reproducing DP properties. Thus, LNGFR(+)THY-1(+) iMCs may provide material for HF bioengineering and drug screening for hair diseases. PMID:28220862

  14. TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis.

    PubMed

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

    2009-01-01

    Dermal papilla cells (DPCs) in the mammalian hair follicle have been shown to develop hair follicles through epithelial-mesenchymal interactions. A cell therapy to regenerate human hair is theoretically possible by expanding autologous human DPCs (hDPCs) and transplanting them into bald skin, though much remains to be overcome before clinical success. In this study, we compared gene signatures of hDPCs at different passages and human dermal fibroblasts, and found transforming growth factor (TGF)-beta(2) to be highly expressed in cultured hDPCs. Keratinocyte conditioned medium, which is known to help preserve the hair-inducing capacity of hDPCs, up-regulated TGF-beta(2) expression of hDPCs and also enhanced their alkaline phosphatase (ALP) activity, a known index for hair-inductive capacity. Through screening of components secreted from keratinocytes, the vitamin D(3) analogue was found to promote TGF-beta(2) expression and ALP activity of hDPCs. In animal hair folliculogenesis models using rat epidermis and expanded hDPCs, inhibition of TGF-beta(2) signalling at the ligand or receptor level significantly impaired hair folliculogenesis and maturation. These results suggest an important role for TGF-beta(2) in hair follicle morphogenesis and provide insights into the establishment of future cell therapies for hair regrowth by transplanting expanded DPCs.

  15. Falsification of the ionic channel theory of hair cell transduction

    PubMed Central

    Rossetto, Michelangelo

    2013-01-01

    The hair cell provides the transduction of mechanical vibrations in the balance and acoustic sense of all vertebrates that swim, walk, or fly. The current theory places hair cell transduction in a mechanically controlled ion channel. Although the theory of a mechanical input modulating the flow of ions through an ion pore has been a useful tool, it is falsified by experimental data in the literature and can be definitively falsified by a proposed experiment. PMID:24563711

  16. Inhibition of Repulsive Guidance Molecule, RGMa, Increases Afferent Synapse Formation with Auditory Hair Cells

    PubMed Central

    Brugeaud, Aurore; Tong, Mingjie; Luo, Li; Edge, Albert S.B.

    2017-01-01

    The peripheral fibers that extend from auditory neurons to hair cells are sensitive to damage, and replacement of the fibers and their afferent synapse with hair cells would be of therapeutic interest. Here, we show that RGMa, a repulsive guidance molecule previously shown to play a role in the development of the chick visual system, is expressed in the developing, newborn, and mature mouse inner ear. The effect of RGMa on synaptogenesis between afferent neurons and hair cells, from which afferent connections had been removed, was assessed. Contact of neural processes with hair cells and elaboration of postsynaptic densities at sites of the ribbon synapse were increased by treatment with a blocking antibody to RGMa, and pruning of auditory fibers to achieve the mature branching pattern of afferent neurons was accelerated. Inhibition by RGMa could thus explain why auditory neurons have a low capacity to regenerate peripheral processes: postnatal spiral ganglion neurons retain the capacity to send out processes that respond to signals for synapse formation, but expression of RGMa postnatally appears to be detrimental to regeneration of afferent hair cell innervation and antagonizes synaptogenesis. Increased synaptogenesis after inhibition of RGMa suggests that manipulation of guidance or inhibitory factors may provide a route to increase formation of new synapses at deafferented hair cells. PMID:24123853

  17. Artificial Hair Cells for Sensing Flows

    NASA Technical Reports Server (NTRS)

    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.

  18. Patterns of light interference produced by damaged cuticle cells in human hair.

    PubMed

    Gamez-Garcia, Manuel; Lu, Yuan

    2007-01-01

    Colorful patterns of light interference have been observed to occur in human hair cuticle cells. The light interference phenomenon has been analyzed by optical microscopy. The strong patterns of light interference appeared only in cuticle cells that had been damaged either mechanically or by thermal stresses. Cuticle cells that were not damaged did not produce this phenomenon. The zones of light interference on the hair surface were seen to extend to cuticle sheath areas whose damage was not apparent when analyzed under the Scanning Electron Microscope. The presence of oils and other hydrophobic materials in the hair had a strong effect in the appearance or disappearance of the interference patterns.

  19. Screening for chemicals that affect hair cell death and survival in the zebrafish lateral line.

    PubMed

    Ou, Henry; Simon, Julian A; Rubel, Edwin W; Raible, David W

    2012-06-01

    The zebrafish lateral line is an efficient model system for the evaluation of chemicals that protect and damage hair cells. Located on the surface of the body, lateral line hair cells are accessible for manipulation and visualization. The zebrafish lateral line system allows rapid screens of large chemical libraries, as well as subsequent thorough evaluation of interesting compounds. In this review, we focus on the results of our previous screens and the evolving methodology of our screens for chemicals that protect hair cells, and chemicals that damage hair cells using the zebrafish lateral line. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing

    PubMed Central

    Taylor, Ruth R.; Jagger, Daniel J.; Saeed, Shakeel R.; Axon, Patrick; Donnelly, Neil; Tysome, James; Moffatt, David; Irving, Richard; Monksfield, Peter; Coulson, Chris; Freeman, Simon R.; Lloyd, Simon K.; Forge, Andrew

    2015-01-01

    Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice. PMID:25818177

  1. Amyloidosis presented with whitening and loss of hair which improved after dimethylsulfoxide (DMSO) treatment.

    PubMed

    Hsieh, S D; Yamamoto, R; Saito, K; Iwamoto, Y; Kuzuya, T; Ohba, S; Kobori, S; Saito, K

    1987-08-01

    A 67-year-old male patient presented with rapid progression of whitening and loss of hair in past 2 months was consulted due to the suspicion of hypothyroidism. He had been told to have cardiomegaly for 3 years. Thyroid function was within normal limit. Prostate biopsy was performed because of prostatic hypertrophy and mild elevation of serum acid phosphatase. Amyloid accumulation was observed in the biopsy specimen. Subsequent skin biopsies revealed the same result. The scalp hair and beard grew and turned to black gradually several months after dimethyl sulfoxide (DMSO) treatment. These findings suggest that some of the manifestation of amyloidosis may respond to DMSO treatment.

  2. Daple coordinates organ-wide and cell-intrinsic polarity to pattern inner-ear hair bundles

    PubMed Central

    Siletti, Kimberly; Hudspeth, A. J.

    2017-01-01

    The establishment of planar polarization by mammalian cells necessitates the integration of diverse signaling pathways. In the inner ear, at least two systems regulate the planar polarity of sensory hair bundles. The core planar cell polarity (PCP) proteins coordinate the orientations of hair cells across the epithelial plane. The cell-intrinsic patterning of hair bundles is implemented independently by the G protein complex classically known for orienting the mitotic spindle. Although the primary cilium also participates in each of these pathways, its role and the integration of the two systems are poorly understood. We show that Dishevelled-associating protein with a high frequency of leucine residues (Daple) interacts with PCP and cell-intrinsic signals. Regulated by the cell-intrinsic pathway, Daple is required to maintain the polarized distribution of the core PCP protein Dishevelled and to position the primary cilium at the abneural edge of the apical surface. Our results suggest that the primary cilium or an associated structure influences the domain of cell-intrinsic signals that shape the hair bundle. Daple is therefore essential to orient and pattern sensory hair bundles. PMID:29229865

  3. Does cochlear implantation and electrical stimulation affect residual hair cells and spiral ganglion neurons?

    PubMed Central

    Coco, Anne; Epp, Stephanie B.; Fallon, James B.; Xu, Jin; Millard, Rodney E.; Shepherd, Robert K.

    2007-01-01

    Increasing numbers of cochlear implant subjects have some level of residual hearing at the time of implantation. The present study examined whether (i) hair cells that have survived one pathological insult (aminoglycoside deafening), can survive and function following long-term cochlear implantation and electrical stimulation (ES); and (ii) chronic ES in these cochleae results in greater trophic support of spiral ganglion neurons (SGNs) compared with cochleae devoid of hair cells. Eight cats, with either partial (n=4) or severe (n=4) sensorineural hearing loss, were bilaterally implanted with scala tympani electrode arrays 2 months after deafening, and received unilateral ES using charge balanced biphasic current pulses for periods of up to 235 days. Frequency-specific compound action potentials and click-evoked auditory brainstem responses (ABRs) were recorded periodically to monitor the residual acoustic hearing. Electrically-evoked ABRs (EABRs) were recorded to confirm the stimulus levels were 3-6 dB above the EABR threshold. On completion of the ES program the cochleae were examined histologically. Partially deafened animals showed no significant increase in acoustic thresholds over the implantation period. Moreover, chronic ES of an electrode array located in the base of the cochlea did not adversely affect hair cells in the middle or apical turns. There was evidence of a small but statistically significant rescue of SGNs in the middle and apical turns of stimulated cochleae in animals with partial hearing. Chronic ES did not, however, prevent a reduction in SGN density for the severely deaf cohort, although SGNs adjacent to the stimulating electrodes did exhibit a significant increase in soma area (p<0.01). In sum, chronic ES in partial hearing animals does not adversely affect functioning residual hair cells apical to the electrode array. Moreover, while there is an increase in the soma area of SGNs close to the stimulating electrodes in severely deaf

  4. Hair transplantation update.

    PubMed

    Rogers, Nicole E

    2015-06-01

    Contemporary hair transplant surgery offers results that are natural and undetectable. It is an excellent treatment option for male and female pattern hair loss. Patients are encouraged to also use medical therapy to help protect their surgical results and prevent ongoing thinning of the surrounding hairs. The two major techniques of donor elliptical harvesting and follicular unit extraction are discussed here. ©2015 Frontline Medical Communications.

  5. Chemotherapy and Hair Loss: What to Expect during Treatment

    MedlinePlus

    ... After treatment Continue gentle hair care. Your new hair growth will be especially fragile and vulnerable to the ... sensitive scalp. Be patient. It's likely that your hair will come back slowly and that it might not look normal right away. But growth takes time, and it also takes time to ...

  6. The use of low-level light therapy in the treatment of androgenetic alopecia and female pattern hair loss.

    PubMed

    Gupta, Aditya K; Daigle, Deanne

    2014-04-01

    Androgenetic alopecia (AGA) or female pattern hair loss (FPHL) is the most common form of hair loss in men and women. Despite its common occurrence, our understanding of the etiology of AGA and FPHL remains incomplete. As such, traditional therapies demonstrate modest efficacies and new therapies continue to be sought. Low-level light therapy (LLLT) is a relatively new technique used to promote hair growth in both men and women with AGA and FPHL. Currently, there exist several LLLT devices marketed for the treatment of alopecia, which claim to stimulate hair growth; yet marketing these devices only requires that safety, not efficacy, be established. A handful of studies have since investigated the efficacy of LLLT for alopecia with mixed results. These studies suffered from power, confounding and analysis issues which resulted in a high risk of bias in LLLT studies. Due to the paucity of well-conducted randomized controlled trials, the efficacy of LLLT devices remains unclear. Randomized controlled trials of LLLT conducted and reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement would greatly increase the credibility of the evidence and clarify the ambiguity of the effectiveness of LLLT in the treatment of AGA and FPHL.

  7. Effect of JNK inhibitor SP600125 on hair cell regeneration in zebrafish (Danio rerio) larvae

    PubMed Central

    Sun, Shaoyang; Wang, Xu; Li, Wenyan; Li, Huawei

    2016-01-01

    The c-Jun amino-terminal kinase (JNK) proteins are a subgroup of the mitogen-activated protein kinase family. They play a complex role in cell proliferation, survival, and apoptosis. Here, we report a novel role of JNK signalling in hair cell regeneration. We eliminated hair cells of 5-day post-fertilization zebrafish larvae using neomycin followed by JNK inhibition with SP600125. JNK inhibition strongly decreased the number of regenerated hair cells in response to neomycin damage. These changes were associated with reduced proliferation. JNK inhibition also increased cleaved caspase-3 activity and induced apoptosis in regenerating neuromasts. Finally, JNK inhibition with SP600125 decreased the expression of genes related to Wnt. Over-activation of the Wnt signalling pathway partly rescued the hair cell regeneration defects induced by JNK inhibition. Together, our findings provide novel insights into the function of JNK and show that JNK inhibition blocks hair cell regeneration by controlling the Wnt signalling pathway. PMID:27438150

  8. [When hair starts to fall out].

    PubMed

    de Lorenzi, Caroline; Quenan, Sandrine

    2018-03-28

    Hair loss causes physical and psychological distress and represents a common motive of consultation both in general practice and dermatology. Causes of hair loss are highly diverse and can lead to a challenging diagnosis, which can delay its management. Knowledge of the main causes and their different mechanisms are thus necessary in order to optimize both the diagnosis and treatment. The purpose of this paper is to describe the main causes of hair loss in order to improve its diagnosis and management.

  9. Effects of a new mild shampoo for preventing hair loss in Asian by a simple hand-held phototrichogram technique.

    PubMed

    Baek, J H; Lee, S Y; Yoo, M; Park, W-S; Lee, S J; Boo, Y C; Koh, J-S

    2011-12-01

    This study was conducted to evaluate the effects of a commercially available shampoo in Korean subjects with alopecia using a simple hand-held phototrichogram technique. Forty-four subjects with alopecia were enrolled and forty subjects continued for 16 weeks. In the test group, total hair counts increased significantly at weeks 8 and 16, and the number of shedding hair significantly decreased at week 16. Terminal hair counts significantly increased at week 8. In the control group, hair thickness and the number of vellus hairs significantly decreased at week 16. The number of total hairs significantly increased in the test group than in the control group at weeks 8 and 16. The number of shedding hairs significantly decreased in the test group than in the control group at week 16. Visual assessment using clinical digital images showed that the number of total hairs appeared to increase although there was no statistical significance. In this study, it was found that the test shampoo could prevent hair loss. © 2011 DERMAPRO Co Ltd. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  10. Bulge Hair Follicle Stem Cells Accelerate Cutaneous Wound Healing in Rats.

    PubMed

    Heidari, Fatemeh; Yari, Abazar; Rasoolijazi, Homa; Soleimani, Mansoureh; Dehpoor, Ahmadreza; Sajedi, Nayereh; Joulai Veijouye, Sanaz; Nobakht, Maliheh

    2016-04-01

    Skin wound healing is a serious clinical problem especially after surgery and severe injury of the skin. Cell therapy is an innovative technique that can be applied to wound healing. One appropriate source of stem cells for therapeutic use is stem cells from the adult bulge of hair follicles. This study examined the effects of adult bulge hair follicle stem cells (HFSC) in wound healing. Hair follicle stem cells were obtained from rat vibrissa and labeled with DiI (Invitrogen, Carlsbad, CA), then special markers were detected using flow cytometry. A full-thickness excisional wound model was created and DiI-labeled HFSC were injected around the wound bed. Wound healing was recorded with digital photographs. Animals were sacrificed at 3, 7, or 14 days after surgery, and were used for the following histological analyses. Flow cytometry analysis showed that HFSC were CD34 positive and nestin positive, but K15 negative. Morphological analysis of HFSC-treated wounds exhibited accelerated wound closure. Histological analysis of hematoxylin and eosin stained and Masson's trichrome-stained photomicrographs showed significantly more re-epithelialization and dermal structural regeneration in HFSC-treated wounds than in the control group. Immunohistochemical analysis of CD31 protein-positive cells showed angiogenesis was also more significant in HFSC-treated wounds than in the control group. Hair follicle stem cells accelerate skin wound healing. Isolating HFSC from a small skin biopsy could repair less-extensive full-thickness skin wounds by autologous stem cells and overcome major challenges regarding the use of stem cells in clinical application, while avoiding immune rejection and ethical concerns.

  11. Hair phenotype in non-syndromic deafness.

    PubMed

    Volo, T; Sathiyaseelan, T; Astolfi, L; Guaran, V; Trevisi, P; Emanuelli, E; Martini, A

    2013-08-01

    The GJB2 gene is located on chromosome 13q12 and it encodes the connexin 26, a transmembrane protein involved in cell-cell attachment of almost all tissues. GJB2 mutations cause autosomal recessive (DFNB1) and sometimes dominant (DFNA3) non-syndromic sensorineural hearing loss. Moreover, it has been demonstrated that connexins are involved in regulation of growth and differentiation of epidermal tissues. Hence, mutations in GJB2 gene, which is responsible for non-syndromic deafness, may be associated with an abnormal skin and hair phenotype. We analyzed hair samples from 96 subjects: a study group of 42 patients with hearing impairments of genetic origin (38 with a non-syndromic form, 4 with a syndromic form), and a control group including 54 people, i.e. 43 patients with other, non-genetic hearing impairments and 11 healthy volunteers aged up to 10 years old. The surface structure of 49 hair samples was normal, whereas in 45 cases it was altered, with a damaged appearance. Two hair samples were considered unclassifiable: one from the patient heterozygotic for the pendrin mutation (Fig. 2C), the other from a patient from Ghana with a R134W mutation (Fig. 2D). Among the 43 altered hair samples, 31 belonged to patients with connexin mutations and the other 12 came from patients without connexin mutations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Long-term hair removal using a 3-millisecond alexandrite laser.

    PubMed

    Laughlin , S A; Dudley, D K

    2000-04-01

    Laser epilation is now used widely as a clinical alternative to electrolysis for the removal of unwanted hair. All of the laser systems presently being used produce a reliable temporary hair loss by inducing telogen. Most of the published studies use follow-up periods of 6 months or less after the last treatment and cannot address the issue of permanency. Since many patients desire permanent hair loss, there is a need for specific information on the exact benefits and limitations of each particular system. The purpose of this study was to assess the degree of hair loss attained by a single treatment with a 3-msec alexandrite laser. A designated period for follow-up was used to address the issue of long-term benefits. A single treatment was carried out on 25 study sites with a 3-msec alexandrite laser at 755 nm using fluences of 30 to 50 joules/cm(2). Hair counts were obtained manually by two independent observers marking terminal hairs under magnification. The counts were repeated using photographic images and the average of the four readings taken. The degree of hair loss was calculated at a time after treatment equal to one complete growth cycle for the particular anatomic site. A second measurement was obtained at a time equal to one growth cycle plus 6 months to determine whether any hair loss had remained stable. The average hair loss at the first follow-up time was 43%, with 60% of sites showing a hair loss of >30%. The hair loss remained stable and the reduction in hair density at both designated times was statistically significant (p <.05). A normal-mode alexandrite laser achieves a long-term alopecia and may result in a permanent loss of terminal hair after one treatment at fluences of 30 to 50 joules/cm(2).

  13. Isolation of Mouse Hair Follicle Bulge Stem Cells and Their Functional Analysis in a Reconstitution Assay.

    PubMed

    Zheng, Ying; Hsieh, Jen-Chih; Escandon, Julia; Cotsarelis, George

    2016-01-01

    The hair follicle (HF) is a dynamic structure readily accessible within the skin, and contains various pools of stem cells that have a broad regenerative potential during normal homeostasis and in response to injury. Recent discoveries demonstrating the multipotent capabilities of hair follicle stem cells and the easy access to skin tissue make the HF an attractive source for isolating stem cells and their subsequent application in tissue engineering and regenerative medicine. Here, we describe the isolation and purification of hair follicle bulge stem cells from mouse skin, and hair reconstitution assays that allows the functional analysis of multipotent stem cells.

  14. ELMOD1 Stimulates ARF6-GTP Hydrolysis to Stabilize Apical Structures in Developing Vestibular Hair Cells.

    PubMed

    Krey, Jocelyn F; Dumont, Rachel A; Wilmarth, Philip A; David, Larry L; Johnson, Kenneth R; Barr-Gillespie, Peter G

    2018-01-24

    Sensory hair cells require control of physical properties of their apical plasma membranes for normal development and function. Members of the ADP-ribosylation factor (ARF) small GTPase family regulate membrane trafficking and cytoskeletal assembly in many cells. We identified ELMO domain-containing protein 1 (ELMOD1), a guanine nucleoside triphosphatase activating protein (GAP) for ARF6, as the most highly enriched ARF regulator in hair cells. To characterize ELMOD1 control of trafficking, we analyzed mice of both sexes from a strain lacking functional ELMOD1 [roundabout ( rda )]. In rda/rda mice, cuticular plates of utricle hair cells initially formed normally, then degenerated after postnatal day 5; large numbers of vesicles invaded the compromised cuticular plate. Hair bundles initially developed normally, but the cell's apical membrane lifted away from the cuticular plate, and stereocilia elongated and fused. Membrane trafficking in type I hair cells, measured by FM1-43 dye labeling, was altered in rda/rda mice. Consistent with the proposed GAP role for ELMOD1, the ARF6 GTP/GDP ratio was significantly elevated in rda/rda utricles compared with controls, and the level of ARF6-GTP was correlated with the severity of the rda/rda phenotype. These results suggest that conversion of ARF6 to its GDP-bound form is necessary for final stabilization of the hair bundle. SIGNIFICANCE STATEMENT Assembly of the mechanically sensitive hair bundle of sensory hair cells requires growth and reorganization of apical actin and membrane structures. Hair bundles and apical membranes in mice with mutations in the Elmod1 gene degenerate after formation, suggesting that the ELMOD1 protein stabilizes these structures. We show that ELMOD1 is a GTPase-activating protein in hair cells for the small GTP-binding protein ARF6, known to participate in actin assembly and membrane trafficking. We propose that conversion of ARF6 into the GDP-bound form in the apical domain of hair cells is

  15. Deletion of PDZD7 disrupts the Usher syndrome type 2 protein complex in cochlear hair cells and causes hearing loss in mice.

    PubMed

    Zou, Junhuang; Zheng, Tihua; Ren, Chongyu; Askew, Charles; Liu, Xiao-Ping; Pan, Bifeng; Holt, Jeffrey R; Wang, Yong; Yang, Jun

    2014-05-01

    Usher syndrome type 2 (USH2) is the predominant form of USH, a leading genetic cause of combined deafness and blindness. PDZD7, a paralog of two USH causative genes, USH1C and USH2D (WHRN), was recently reported to be implicated in USH2 and non-syndromic deafness. It encodes a protein with multiple PDZ domains. To understand the biological function of PDZD7 and the pathogenic mechanism caused by PDZD7 mutations, we generated and thoroughly characterized a Pdzd7 knockout mouse model. The Pdzd7 knockout mice exhibit congenital profound deafness, as assessed by auditory brainstem response, distortion product otoacoustic emission and cochlear microphonics tests, and normal vestibular function, as assessed by their behaviors. Lack of PDZD7 leads to the disorganization of stereocilia bundles and a reduction in mechanotransduction currents and sensitivity in cochlear outer hair cells. At the molecular level, PDZD7 determines the localization of the USH2 protein complex, composed of USH2A, GPR98 and WHRN, to ankle links in developing cochlear hair cells, likely through its direct interactions with these three proteins. The localization of PDZD7 to the ankle links of cochlear hair bundles also relies on USH2 proteins. In photoreceptors of Pdzd7 knockout mice, the three USH2 proteins largely remain unchanged at the periciliary membrane complex. The electroretinogram responses of both rod and cone photoreceptors are normal in knockout mice at 1 month of age. Therefore, although the organization of the USH2 complex appears different in photoreceptors, it is clear that PDZD7 plays an essential role in organizing the USH2 complex at ankle links in developing cochlear hair cells. GenBank accession numbers: KF041446, KF041447, KF041448, KF041449, KF041450, KF041451.

  16. Role of the array geometry in multi-bilayer hair cell sensors

    NASA Astrophysics Data System (ADS)

    Tamaddoni, Nima J.; Sarles, Stephen A.

    2014-03-01

    Recently, a bio-inspired, synthetic membrane-based hair cell sensor was fabricated and characterized. This sensor generates current in response to mechanical stimuli, such as airflow or free vibration, which perturb the sensor's hair. Vibration transferred from the hair to a lipid membrane (lipid bilayer) causes a voltage-dependent time rate of change in electrical capacitance of the membrane, which produces measurable current. Studies to date have been performed on systems containing only two droplets and a single bilayer, even though an array of multiple bilayers can be formed with more than 2 droplets. Thus, it is yet to be determined how multiple lipid bilayers affect the sensing response of a membrane-based hair cell sensor. In this work, we assemble serial droplet arrays with more than 1 bilayer to experimentally study the current generated by each membrane in response to perturbation of a single hair element. Two serial array configurations are studied: The first consists of a serial array of 3 bilayers formed using 4 droplets with the hair positioned in an end droplet. The second configuration consists of 3 droplets and 2 bilayers in series with the hair positioned in the central droplet. In serial arrays of up to four droplets, we observe that mechanotransduction of the hair's motion into a capacitive current occurs at every membrane, with bilayers positioned adjacent to the droplet containing the hair generating the largest sensing current. The measured currents suggest the total current generated by all bilayers in a 4-droplet, 3-bilaye array is greater than the current produced by a single-membrane sensor and similar in magnitude to the sum of currents output by 3, single-bilayer sensors operated independently. Moreover, we learned that bilayers positioned on the same side of the hair produce sensing currents that are in-phase, whereas bilayers positioned on opposite sides of the droplet containing the hair generate out-of-phase responses.

  17. Immunofluorescence findings in rapid whitening of scalp hair.

    PubMed

    Guin, J D; Kumar, V; Petersen, B H

    1981-09-01

    Rapid whitening of scalp hair developed during a three-month period along with a diffuse, subtotal alopecia in a patient. Immunofluorescence microscopy of biopsy material showed prominent deposits of IgG and IgM in a granular pattern in the epithelium of the lower portions of hair follicles. Some return of the color and amount of scalp hair occurred within a year, but occasional bouts of hair loss continued to occur. It is theorized that the rapid graying was caused by a selective loss of pigmented hair, which was perhaps caused by an immunologic mechanism. Some of the findings suggest that the cause of this patient's loss of hair color may be different from those of patients who have been previously described as having rapid whitening of scalp hair because of alopecia areata or vitiligo.

  18. Maintained expression of the planar cell polarity molecule Vangl2 and reformation of hair cell orientation in the regenerating inner ear.

    PubMed

    Warchol, Mark E; Montcouquiol, Mireille

    2010-09-01

    The avian inner ear possesses a remarkable ability to regenerate sensory hair cells after ototoxic injury. Regenerated hair cells possess phenotypes and innervation that are similar to those found in the undamaged ear, but little is known about the signaling pathways that guide hair cell differentiation during the regenerative process. The aim of the present study was to examine the factors that specify the orientation of hair cell stereocilia bundles during regeneration. Using organ cultures of the chick utricle, we show that hair cells are properly oriented after having regenerated entirely in vitro and that orientation is not affected by surgical removal of the striolar reversal zone. These results suggest that the orientation of regenerating stereocilia is not guided by the release of a diffusible morphogen from the striolar reversal zone but is specified locally within the regenerating sensory organ. In order to determine the nature of the reorientation cues, we examined the expression patterns of the core planar cell polarity molecule Vangl2 in the normal and regenerating utricle. We found that Vangl2 is asymmetrically expressed on cells within the sensory epithelium and that this expression pattern is maintained after ototoxic injury and throughout regeneration. Notably, treatment with a small molecule inhibitor of c-Jun-N-terminal kinase disrupted the orientation of regenerated hair cells. Both of these results are consistent with the hypothesis that noncanonical Wnt signaling guides hair cell orientation during regeneration.

  19. Model-based analysis of the torsional loss modulus in human hair and of the effects of cosmetic processing.

    PubMed

    Wortmann, Franz J; Wortmann, Gabriele; Haake, Hans-Martin; Eisfeld, Wolf

    Torsional analysis of single human hairs is especially suited to determine the properties of the cuticle and its changes through cosmetic processing. The two primary parameters, which are obtained by free torsional oscillation using the torsional pendulum method, are storage ( G ') and loss modulus ( G ″). Based on previous work on G ', the current investigation focuses on G ″. The results show an increase of G ″ with a drop of G ' and vice versa , as is expected for a viscoelastic material well below its glass transition. The overall power of G ″ to discriminate between samples is quite low. This is attributed to the systematic decrease of the parameter values with increasing fiber diameter, with a pronounced correlation between G ″ and G '. Analyzing this effect on the basis of a core/shell model for the cortex/cuticle structure of hair by nonlinear regression leads to estimates for the loss moduli of cortex ( G ″ co ) and cuticle ( G ″ cu ). Although the values for G ″ co turn out to be physically not plausible, due to limitations of the applied model, those for G ″ cu are considered as generally realistic against relevant literature values. Significant differences between the loss moduli of the cuticle for the different samples provide insight into changes of the torsional energy loss due to the cosmetic processes and products, contributing toward a consistent view of torsional energy storage and loss, namely, in the cuticle of hair.

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

    NASA Technical Reports Server (NTRS)

    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.

  1. Comparative Hair Restorer Efficacy of Medicinal Herb on Nude (Foxn1nu) Mice

    PubMed Central

    Begum, Shahnaz; Lee, Mi Ra; Gu, Li Juan; Hossain, Md. Jamil; Kim, Hyun Kyoung; Sung, Chang Keun

    2014-01-01

    Eclipta alba (L.) Hassk, Asiasarum sieboldii (Miq.) F. Maek (Asiasari radix), and Panax ginseng C. A. Mey (red ginseng) are traditionally acclaimed for therapeutic properties of various human ailments. Synergistic effect of each standardized plant extract was investigated for hair growth potential on nude mice, as these mutant mice genetically lack hair due to abnormal keratinization. Dried plant samples were ground and extracted by methanol. Topical application was performed on the back of nude mice daily up to completion of two hair growth generations. The hair density and length of Eclipta alba treated mice were increased significantly (P > 0.001) than control mice. Hair growth area was also distinctly visible in Eclipta alba treated mice. On the other hand, Asiasari radix and Panax ginseng treated mice developing hair loss were recognized from the abortive boundaries of hair coverage. Histomorphometric observation of nude mice skin samples revealed an increase in number of hair follicles (HFs). The presence of follicular keratinocytes was confirmed by BrdU labeling, S-phase cells in HFs. Therefore, Eclipta alba extract and/or phytochemicals strongly displayed incomparability of hair growth promotion activity than others. Thus, the standardized Eclipta alba extract can be used as an effective, alternative, and complementary treatment against hair loss. PMID:25478567

  2. Prickle1 regulates neurite outgrowth of apical spiral ganglion neurons but not hair cell polarity in the murine cochlea

    PubMed Central

    Kersigo, Jennifer; Wu, Shu; Fritzsch, Bernd; Bassuk, Alexander G.

    2017-01-01

    In the mammalian organ of Corti (OC), the stereocilia on the apical surface of hair cells (HCs) are uniformly organized in a neural to abneural axis (or medial-laterally). This organization is regulated by planar cell polarity (PCP) signaling. Mutations of PCP genes, such as Vangl2, Dvl1/2, Celsr1, and Fzd3/6, affect the formation of HC orientation to varying degrees. Prickle1 is a PCP signaling gene that belongs to the prickle / espinas / testin family. Prickle1 protein is shown to be asymmetrically localized in the HCs of the OC, and this asymmetric localization is associated with loss of PCP in Smurf mutants, implying that Prickle1 is involved in HC PCP development in the OC. A follow-up study found no PCP polarity defects after loss of Prickle1 (Prickle1-/-) in the cochlea. We show here strong Prickle1 mRNA expression in the spiral ganglion by in situ hybridization and β-Gal staining, and weak expression in the OC by β-Gal staining. Consistent with this limited expression in the OC, cochlear HC PCP is unaffected in either Prickle1C251X/C251X mice or Prickle1f/f; Pax2-cre conditional null mice. Meanwhile, type II afferents of apical spiral ganglion neurons (SGN) innervating outer hair cells (OHC) have unusual neurite growth. In addition, afferents from the apex show unusual collaterals in the cochlear nuclei that overlap with basal turn afferents. Our findings argue against the role of Prickle1 in regulating hair cell polarity in the cochlea. Instead, Prickle1 regulates the polarity-related growth of distal and central processes of apical SGNs. PMID:28837644

  3. Active Outer Hair Cells Affect the Sound-Evoked Vibration of the Reticular Lamina

    NASA Astrophysics Data System (ADS)

    Jacob, Stefan; Fridberger, Anders

    2011-11-01

    It is well established that the organ of Corti uses active mechanisms to enhance its sensitivity and frequency selectivity. Two possible mechanisms have been identified, both capable of producing mechanical forces, which can alter the sound-evoked vibration of the hearing organ. However, little is known about the effect of these forces on the sound-evoked vibration pattern of the reticular lamina. Current injections into scala media were used to alter the amplitude of the active mechanisms in the apex of the guinea pig temporal bone. We used time-resolved confocal imaging to access the vibration pattern of individual outer hair cells. During positive current injection the the sound-evoked vibration of outer hair cell row three increased while row one showed a small decrease. Negative currents reversed the observed effect. We conclude that the outer hair cell mediated modification of reticular lamina vibration patterns could contribute to the inner hair cell stimulation.

  4. FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells.

    PubMed

    Nguyen, Minh Binh; Cohen, Idan; Kumar, Vinod; Xu, Zijian; Bar, Carmit; Dauber-Decker, Katherine L; Tsai, Pai-Chi; Marangoni, Pauline; Klein, Ophir D; Hsu, Ya-Chieh; Chen, Ting; Mikkola, Marja L; Ezhkova, Elena

    2018-06-13

    Merkel cells are innervated mechanosensory cells responsible for light-touch sensations. In murine dorsal skin, Merkel cells are located in touch domes and found in the epidermis around primary hairs. While it has been shown that Merkel cells are skin epithelial cells, the progenitor cell population that gives rise to these cells is unknown. Here, we show that during embryogenesis, SOX9-positive (+) cells inside hair follicles, which were previously known to give rise to hair follicle stem cells (HFSCs) and cells of the hair follicle lineage, can also give rise to Merkel Cells. Interestingly, while SOX9 is critical for HFSC specification, it is dispensable for Merkel cell formation. Conversely, FGFR2 is required for Merkel cell formation but is dispensable for HFSCs. Together, our studies uncover SOX9(+) cells as precursors of Merkel cells and show the requirement for FGFR2-mediated epithelial signalling in Merkel cell specification.

  5. ROOT HAIR DEFECTIVE SIX-LIKE Class I Genes Promote Root Hair Development in the Grass Brachypodium distachyon

    PubMed Central

    Kim, Chul Min

    2016-01-01

    Genes encoding ROOT HAIR DEFECTIVE SIX-LIKE (RSL) class I basic helix loop helix proteins are expressed in future root hair cells of the Arabidopsis thaliana root meristem where they positively regulate root hair cell development. Here we show that there are three RSL class I protein coding genes in the Brachypodium distachyon genome, BdRSL1, BdRSL2 and BdRSL3, and each is expressed in developing root hair cells after the asymmetric cell division that forms root hair cells and hairless epidermal cells. Expression of BdRSL class I genes is sufficient for root hair cell development: ectopic overexpression of any of the three RSL class I genes induces the development of root hairs in every cell of the root epidermis. Expression of BdRSL class I genes in root hairless Arabidopsis thaliana root hair defective 6 (Atrhd6) Atrsl1 double mutants, devoid of RSL class I function, restores root hair development indicating that the function of these proteins has been conserved. However, neither AtRSL nor BdRSL class I genes is sufficient for root hair development in A. thaliana. These data demonstrate that the spatial pattern of class I RSL activity can account for the pattern of root hair cell differentiation in B. distachyon. However, the spatial pattern of class I RSL activity cannot account for the spatial pattern of root hair cells in A. thaliana. Taken together these data indicate that that the functions of RSL class I proteins have been conserved among most angiosperms—monocots and eudicots—despite the dramatically different patterns of root hair cell development. PMID:27494519

  6. Effects of Mechanical Loading on the Dynamics of Hair-Cell Stereociliary Bundles

    NASA Astrophysics Data System (ADS)

    Fredrickson, Lea

    Hearing is remarkably sensitive and still not entirely understood. Hair cells of the inner ear are the mechano-electrical transducers of sound and understanding how they function is essential to the understanding of hearing in general. Spontaneous oscillations exhibited by stereociliary bundles of the bullfrog sacculus provide a useful probe for the study of the hair cells' internal dynamic state. In this work we study the effects of mechanical loading on these hair-cell bundles in order to study their dynamics. When applying stiffness loads, we find that the spontaneous oscillation profile changes from multimode to single mode with light loading, and decreases in amplitude and increases in frequency with stiffer loads. We also find that tuning decreases with increasing load such that at loads comparable to in vivo conditions the tuning is flat. We further explore loading via deflections to hair cell bundles, both in the form of steady-state offsets and slow ramps. We find that steady state offsets lead to significant modulation of the characteristic frequency of response, decreasing the frequency in the channels closed direction (negative) and increasing it in the channels open direction (positive). Attachment to the overlying membrane was found, in vitro, to affect bundle offset position in hair cells of the bullfrog sacculus. Application of similar offsets on free-standing, spontaneously oscillating hair bundles shows modulation of their dynamic state, i.e. oscillation profile, characteristic frequency, and response to stimulus. Large offsets are found to arrest spontaneous oscillations, which recover upon reversal of the stimulus. The dynamical state of the hair bundle is dependent on both the history and direction of the offset stimulus. Oscillation suppression occurs much more readily in the negative direction and the bundle behavior approaching quiescence is distinct from that in the positive direction. With the change in spontaneous oscillation frequency

  7. Controlling Mitochondrial Dynamics to Mitigate Noise-Induced Hearing Loss

    DTIC Science & Technology

    2017-10-01

    protection against outer hair cell loss at the high frequency responsive region of the organ of Corti was observed. Importantly, these findings demonstrated...a high dose would be detrimental to hearing sensitivity or to outer hair cell viability. The 25 and 100 µM doses were similar to the 50 µM dose in...Completion of outer hair cell counts on the 200 µM study group revealed that this higher dose did not reduce OHC survival in the treated ear

  8. Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin.

    PubMed

    Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X

    2006-01-12

    Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.

  9. Dissecting the bulge in hair regeneration

    PubMed Central

    Ito, Mayumi; Myung, Peggy

    2012-01-01

    The adult hair follicle houses stem cells that govern the cyclical growth and differentiation of multiple cell types that collectively produce a pigmented hair. Recent studies have revealed that hair follicle stem cells are heterogeneous and dynamic throughout the hair cycle. Moreover, interactions between heterologous stem cells, including both epithelial and melanocyte stem cells, within the hair follicle are just now being explored. This review will describe how recent findings have expanded our understanding of the development, organization, and regeneration of hair follicle stem cells. At a basic level, this review is intended to help construct a reference point to integrate the surge of studies on the molecular mechanisms that regulate these cells. PMID:22293183

  10. Comparing the Effects of Zinc Sulfate, Calcium Pantothenate, Their Combination and Minoxidil Solution Regimens on Controlling Hair Loss in Women: A Randomized Controlled Trial.

    PubMed

    Siavash, Mansour; Tavakoli, Fereshteh; Mokhtari, Fatemeh

    2017-01-01

    This study was conducted to evaluate the combination of oral supplements with 2% minoxidil solution in four groups of women with hair loss. A prospective, randomized controlled trial was conducted from July to December 2016 in dermatology clinics affiliated to Isfahan University of Medical Sciences. A total of 73, 15-45-year-old, women with hair loss participated in this 4-month study. Simple randomization using Random Allocation Software was done to put the participants in four groups to receive coadministration of zinc sulfate and calcium pantothenate, zinc sulfate, calcium pantothenate, and 2% minoxidil solution. The primary endpoint was the change in hair density and diameter measured by dermatoscope. Secondary endpoints included the researcher's evaluation, dermatologist's opinion - which was blinded to the study - from comparing the participants' photographs before and after treatment and finally, overall changes in hair density measured by participants' self-assessment. Seventy-three women participated in this study. Primary hair count and thickness were 118.5 ± 10 hairs/cm 2 and 58.8 ± 5.8 μ that changed to 124 ± 11 hairs/cm 2 and 62.3 ± 4.3 μ respectively ( P < 0.001) which in the zinc plus pantothenate group these changes were from 118.6 ± 9.9 hairs/cm 2 to 121.9 ± 11.1 hairs/cm 2 ( P = 0.042) and from 62.2 ± 6.6 μ to 64.0 ± 5.0 μ ( P = 0.126), respectively. Hair density increments were more obvious in the minoxidil group, and hair thickness increments were more obvious in pantothenate group. Participants' satisfaction was 85% in the combination therapy which was more than other groups. Participants' satisfaction, author's and blind dermatologist's opinion showed a significant correlation ( P = 0.0001). Based on the participants' satisfaction, the combination of zinc sulfate and calcium pantothenate when administered in a pulse therapy way could be a good choice for hair loss controlling in initial stages.

  11. Inositol bisphosphate and inositol trisphosphate inhibit cell-to-cell passage of carboxyfluorescein in staminal hairs ofSetcreasea purpurea.

    PubMed

    Tucker, E B

    1988-06-01

    pH-buffered carboxyfluorescein (Buffered-CF) alone (control), or Buffered-CF solutions containing one of the following: (1)D-myo-inositol (I); (2)D-myo-inositol 2-monophosphate (IP1); (3)D-myo-inositol 1,4-bisphosphate (IP2); (4)D-myo-inositol 1,4,5-trisphosphate (IP3); (5)D-fructose 2,6-diphosphate (F-2,6P2) were microinjected into the terminal cells of staminal hairs ofSetcreasea purpurea Boom. Passage of the CF from this terminal cell along the chain of cells towards the filament was monitored for 5 min using fluorescence microscopy and quantified using computer-assisted fluorescence-intensity video analysis. Cell-to-cell transport of CF in hairs microinjected with Buffered-CF containing either I, IP1 or F-2,6P2 was similar to that in hairs microinjected with Buffered-CF only. On the other hand, cell-to-cell transport of CF in hairs microinjected with Buffered-CF containing either IP2 or IP3 was inhibited. These results indicate that polyphosphoinositols may be involved in the regulation of intercellular transport of low-molecular-weight, hydrophilic molecules in plants.

  12. Hair organ regeneration via the bioengineered hair follicular unit transplantation

    PubMed Central

    Asakawa, Kyosuke; Toyoshima, Koh-ei; Ishibashi, Naoko; Tobe, Hirofumi; Iwadate, Ayako; Kanayama, Tatsuya; Hasegawa, Tomoko; Nakao, Kazuhisa; Toki, Hiroshi; Noguchi, Shotaro; Ogawa, Miho; Sato, Akio; Tsuji, Takashi

    2012-01-01

    Organ regenerative therapy aims to reproduce fully functional organs to replace organs that have been lost or damaged as a result of disease, injury, or aging. For the fully functional regeneration of ectodermal organs, a concept has been proposed in which a bioengineered organ is developed by reproducing the embryonic processes of organogenesis. Here, we show that a bioengineered hair follicle germ, which was reconstituted with embryonic skin-derived epithelial and mesenchymal cells and ectopically transplanted, was able to develop histologically correct hair follicles. The bioengineered hair follicles properly connected to the host skin epithelium by intracutaneous transplantation and reproduced the stem cell niche and hair cycles. The bioengineered hair follicles also autonomously connected with nerves and the arrector pili muscle at the permanent region and exhibited piloerection ability. Our findings indicate that the bioengineered hair follicles could restore physiological hair functions and could be applicable to surgical treatments for alopecia. PMID:22645640

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

    PubMed Central

    Plikus, Maksim V.

    2014-01-01

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

  14. Developing an active artificial hair cell using nonlinear feedback control

    NASA Astrophysics Data System (ADS)

    Joyce, Bryan S.; Tarazaga, Pablo A.

    2015-09-01

    The hair cells in the mammalian cochlea convert sound-induced vibrations into electrical signals. These cells have inspired a variety of artificial hair cells (AHCs) to serve as biologically inspired sound, fluid flow, and acceleration sensors and could one day replace damaged hair cells in humans. Most of these AHCs rely on passive transduction of stimulus while it is known that the biological cochlea employs active processes to amplify sound-induced vibrations and improve sound detection. In this work, an active AHC mimics the active, nonlinear behavior of the cochlea. The AHC consists of a piezoelectric bimorph beam subjected to a base excitation. A feedback control law is used to reduce the linear damping of the beam and introduce a cubic damping term which gives the AHC the desired nonlinear behavior. Model and experimental results show the AHC amplifies the response due to small base accelerations, has a higher frequency sensitivity than the passive system, and exhibits a compressive nonlinearity like that of the mammalian cochlea. This bio-inspired accelerometer could lead to new sensors with lower thresholds of detection, improved frequency sensitivities, and wider dynamic ranges.

  15. Characterizing human vestibular sensory epithelia for experimental studies: new hair bundles on old tissue and implications for therapeutic interventions in ageing.

    PubMed

    Taylor, Ruth R; Jagger, Daniel J; Saeed, Shakeel R; Axon, Patrick; Donnelly, Neil; Tysome, James; Moffatt, David; Irving, Richard; Monksfield, Peter; Coulson, Chris; Freeman, Simon R; Lloyd, Simon K; Forge, Andrew

    2015-06-01

    Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Valproic Acid Induces Hair Regeneration in Murine Model and Activates Alkaline Phosphatase Activity in Human Dermal Papilla Cells

    PubMed Central

    Lee, Soung-Hoon; Yoon, Juyong; Shin, Seung Ho; Zahoor, Muhamad; Kim, Hyoung Jun; Park, Phil June; Park, Won-Seok; Min, Do Sik; Kim, Hyun-Yi; Choi, Kang-Yell

    2012-01-01

    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 BeCl2 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. PMID:22506014

  17. Concurrent gradients of ribbon volume and AMPA-receptor patch volume in cochlear afferent synapses on gerbil inner hair cells.

    PubMed

    Zhang, Lichun; Engler, Sina; Koepcke, Lena; Steenken, Friederike; Köppl, Christine

    2018-07-01

    The Mongolian gerbil is a classic animal model for age-related hearing loss. As a prerequisite for studying age-related changes, we characterized cochlear afferent synaptic morphology in young adult gerbils, using immunolabeling and quantitative analysis of confocal microscopic images. Cochlear wholemounts were triple-labeled with a hair-cell marker, a marker of presynaptic ribbons, and a marker of postsynaptic AMPA-type glutamate receptors. Seven cochlear positions covering an equivalent frequency range from 0.5 - 32 kHz were evaluated. The spatial positions of synapses were determined in a coordinate system with reference to their individual inner hair cell. Synapse numbers confirmed previous reports for gerbils (on average, 20-22 afferents per inner hair cell). The volumes of presynaptic ribbons and postsynaptic glutamate receptor patches were positively correlated: larger ribbons associated with larger receptor patches and smaller ribbons with smaller patches. Furthermore, the volumes of both presynaptic ribbons and postsynaptic receptor patches co-varied along the modiolar-pillar and the longitudinal axes of their hair cell. The gradients in ribbon volume are consistent with previous findings in cat, guinea pig, mouse and rat and further support a role in differentiating the physiological properties of type I afferents. However, the positive correlation between the volumes of pre- and postsynaptic elements in the gerbil is different to the opposing gradients found in the mouse, suggesting species-specific differences in the postsynaptic AMPA receptors that are unrelated to the fundamental classes of type I afferents. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Xyloside primed glycosaminoglycans alter hair bundle micromechanical coupling and synaptic transmission: Pharmacokinetics

    NASA Astrophysics Data System (ADS)

    Holman, Holly A.; Tran, Vy M.; Nguyen, Lynn Y.; Arungundram, Sailaja; Kalita, Mausam; Kuberan, Balagurunathan; Rabbitt, Richard D.

    2015-12-01

    Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of hair-cell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observed around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear.

  19. Xyloside primed glycosaminoglycans alter hair bundle micromechanical coupling and synaptic transmission: Pharmacokinetics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Holman, Holly A.; Nguyen, Lynn Y.; Tran, Vy M.

    Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of hair-cell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observedmore » around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear.« less

  20. Ethnic hair disorders.

    PubMed

    Lindsey, Scott F; Tosti, Antonella

    2015-01-01

    The management of hair and scalp conditions is difficult in any patient, especially given the emotional and psychological implications of hair loss. This undertaking becomes even more challenging in the ethnic patient. Differences in hair care practices, hair shaft morphology, and follicular architecture add complexity to the task. It is imperative that the physician be knowledgeable about these practices and the phenotypic differences seen in ethnic hair in order to appropriately diagnose and treat these patients. In this chapter, we will discuss cultural practices and morphologic differences and explain how these relate to the specific disorders seen in ethnic populations. We will also review the most prominent of the ethnic hair conditions including acquired trichorrhexis nodosa, traction alopecia, central centrifugal cicatricial alopecia, pseudofolliculitis barbae, dissecting cellulitis, and acne keloidalis nuchae. © 2015 S. Karger AG, Basel.

  1. Drug discovery for alopecia: gone today, hair tomorrow.

    PubMed

    Santos, Zenildo; Avci, Pinar; Hamblin, Michael R

    2015-03-01

    Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8(+)NK group 2D-positive (NKG2D(+)) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.

  2. Drug discovery for alopecia: gone today, hair tomorrow

    PubMed Central

    Santos, Zenildo; Avci, Pinar; Hamblin, Michael R

    2015-01-01

    Introduction Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. Areas covered In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8+NK group 2D-positive (NKG2D+) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. Expert opinion The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play. PMID:25662177

  3. Modulating hair follicle size with Wnt10b-DKK1 pair during hair regeneration

    PubMed Central

    Lei, Mingxing; Guo, Haiying; Qiu, Weiming; Lai, Xiangdong; Yang, Tian; Widelitz, Randall B.; Chuong, Cheng-Ming; Lian, Xiaohua; Yang, Li

    2015-01-01

    Hair follicles have characteristic sizes corresponding to their cycle specific stage. However, how the anagen hair follicle specifies its size remains elusive. Here, we show that in response to prolonged ectopic Wnt10b-mediated β-catenin activation, regenerating anagen hair follicles grow larger in size. In particular, the hair bulb, dermal papilla and hair shaft become enlarged. While the formation of different hair types (Guard, Awl, Auchene, and Zigzag) is unaffected. Interestingly, we found the effect of exogenous WNT10b was mainly on Zigzag and less on the other kinds of hairs. We observed dramatically enhanced proliferation within the matrix, DP and hair shaft of the enlarged AdWnt10b-treated hair follicles compared with those of normal hair follicles at P98. Furthermore, expression of CD34, a specific hair stem cell marker, was increased in its number to the bulge region after AdWnt10b treatment. Ectopic expression of CD34 throughout the ORS region was also observed. Many CD34 positive hair stem cells were actively proliferating in AdWnt10b-induced hair follicles. Importantly, subsequent co-treatment with the Wnt inhibitor, DKK1, reduced hair follicle enlargement, decreased proliferation and maintained proper hair stem cell localization. Moreover, injection of DKK1 during early anagen significantly reduced the width of prospective hairs. Together, these findings strongly suggest that a balance of Wnt10b/DKK1 governs reciprocal signaling between cutaneous epithelium and mesenchyme to regulate proper hair follicle size. PMID:24750467

  4. A Critical Assessment of the Evidence for Low-Level Laser Therapy in the Treatment of Hair Loss.

    PubMed

    Gupta, Aditya K; Foley, Kelly A

    2017-02-01

    Low-level laser therapy (LLLT) is currently in use to stimulate hair growth and is quickly gaining in popularity due to the ease of use and absence of side effects. In 2015 alone, the number of LLLT devices with the Food and Drug Administration clearance has doubled. To consolidate evidence and establish which data are still required for the widespread acceptance of LLLT for hair loss therapy. A thorough search of the PubMed database was conducted to obtain studies investigating LLLT for androgenetic alopecia in men and women. Nine trials were identified for comb and helmet/cap devices, five of which were randomized controlled trials. Data comparison across LLLT trials and with traditional hair loss therapy (minoxidil, finasteride) was not straight forward because there was a lack of visual evidence, sample sizes were low, and there were large variations in study duration and efficacy measurements. There are a number of unanswered questions about the optimum treatment regimen, including maintenance treatment and the long-term consequences of LLLT use. Moving forward, protocols should be standardized across trials. Moreover, it is recommended that future trials include visual evidence and trial duration be expanded to 12 months.

  5. Safety and efficacy analysis of liposomal insulin-like growth factor-1 in a fluid gel formulation for hair-loss treatment in a hamster model.

    PubMed

    Castro, R F; Azzalis, L A; Feder, D; Perazzo, F F; Pereira, E C; Junqueira, V B C; Rocha, K C; Machado, C D'A; Paschoal, F C; Gnann, L A; Fonseca, F L A

    2012-12-01

    Insulin-like growth factor (IGF)-1 has shown some interesting results in studies examining its use as a hair-loss treatment. IGF-1 works by regulating cellular proliferation and migration during the development of hair follicles. Hepatotoxicity and myelotoxicity were evaluated in hamsters (Mesocricetus auratus) after topical application of the liquid gel vehicle (placebo), 1% IGF-1 or 3% IGF-1. No significant difference in the levels of aspartate aminotransferase or alanine aminotransferase was found between the control and treated groups. ELISA did not shown any increase in the plasma level of IGF-1. A haematopoietic niche was found, but it was not associated with myelotoxicity. Efficacy was determined by dermatoscopy analysis of hair density and microscopy analysis of hair diameter, with hair found to be thicker and with more rapid growth in the 3% group than in either the 1% group or the control group. These results strongly suggest that liposomal IGF-1 in a liquid gel formulation is a safe and efficient treatment for hair loss. © The Author(s). CED © 2012 British Association of Dermatologists.

  6. S-nitrosoglutathione promotes cell wall remodelling, alters the transcriptional profile and induces root hair formation in the hairless root hair defective 6 (rhd6) mutant of Arabidopsis thaliana.

    PubMed

    Moro, Camila Fernandes; Gaspar, Marilia; da Silva, Felipe Rodrigues; Pattathil, Sivakumar; Hahn, Michael G; Salgado, Ione; Braga, Marcia Regina

    2017-03-01

    Nitric oxide (NO) exerts pleiotropic effects on plant development; however, its involvement in cell wall modification during root hair formation (RHF) has not yet been addressed. Here, mutants of Arabidopsis thaliana with altered root hair phenotypes were used to assess the involvement of S-nitrosoglutathione (GSNO), the primary NO source, in cell wall dynamics and gene expression in roots induced to form hairs. GSNO and auxin restored the root hair phenotype of the hairless root hair defective 6 (rhd6) mutant. A positive correlation was observed between increased NO production and RHF induced by auxin in rhd6 and transparent testa glabra (ttg) mutants. Deposition of an epitope within rhamnogalacturonan-I recognized by the CCRC-M2 antibody was delayed in root hair cells (trichoblasts) compared with nonhair cells (atrichoblasts). GSNO, but not auxin, restored the wild-type root glycome and transcriptome profiles in rhd6, modulating the expression of a large number of genes related to cell wall composition and metabolism, as well as those encoding ribosomal proteins, DNA and histone-modifying enzymes and proteins involved in post-translational modification. Our results demonstrate that NO plays a key role in cell wall remodelling in trichoblasts and suggest that it also participates in chromatin modification in root cells of A. thaliana. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  7. Utilizing electromagnetic radiation for hair growth: a critical review of phototrichogenesis.

    PubMed

    Kalia, Sunil; Lui, Harvey

    2013-01-01

    Hair loss has a high prevalence in the general population and can have significant medical and psychological sequelae. Pattern hair loss and alopecia areata represent the major reasons patients present to dermatologists in relation to hair loss. Because conventional treatment options are generally incompletely effective, novel methods for hair grown induction are being developed. The role of using electromagnetic radiation, including low-level laser therapy for the management of hair loss through phototrichogenesis, is reviewed in this article. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  8. CD34 Expression by Hair Follicle Stem Cells Is Required for Skin Tumor Development in Mice

    PubMed Central

    Trempus, Carol S.; Morris, Rebecca J.; Ehinger, Matthew; Elmore, Amy; Bortner, Carl D.; Ito, Mayumi; Cotsarelis, George; Nijhof, Joanne G.W.; Peckham, John; Flagler, Norris; Kissling, Grace; Humble, Margaret M.; King, Leon C.; Adams, Linda D.; Desai, Dhimant; Amin, Shantu; Tennant, Raymond W.

    2007-01-01

    The cell surface marker CD34 marks mouse hair follicle bulge cells, which have attributes of stem cells, including quiescence and multipotency. Using a CD34 knockout (KO) mouse, we tested the hypothesis that CD34 may participate in tumor development in mice because hair follicle stem cells are thought to be a major target of carcinogens in the two-stage model of mouse skin carcinogenesis. Following initiation with 200 nmol 7,12-dimethylbenz(a)anthracene (DMBA), mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Under these conditions, CD34KO mice failed to develop papillomas. Increasing the initiating dose of DMBA to 400 nmol resulted in tumor development in the CD34KO mice, albeit with an increased latency and lower tumor yield compared with the wild-type (WT) strain. DNA adduct analysis of keratinocytes from DMBA-initiated CD34KO mice revealed that DMBA was metabolically activated into carcinogenic diol epoxides at both 200 and 400 nmol. Chronic exposure to TPA revealed that CD34KO skin developed and sustained epidermal hyperplasia. However, CD34KO hair follicles typically remained in telogen rather than transitioning into anagen growth, confirmed by retention of bromodeoxyuridine-labeled bulge stem cells within the hair follicle. Unique localization of the hair follicle progenitor cell marker MTS24 was found in interfollicular basal cells in TPA-treated WT mice, whereas staining remained restricted to the hair follicles of CD34KO mice, suggesting that progenitor cells migrate into epidermis differently between strains. These data show that CD34 is required for TPA-induced hair follicle stem cell activation and tumor formation in mice. PMID:17483328

  9. Influence of Th2 cells on hair cycle/growth after repeated cutaneous application of hapten.

    PubMed

    Sugita, K; Nomura, T; Ikenouchi-Sugita, A; Ito, T; Nakamura, M; Miyachi, Y; Tokura, Y; Kabashima, K

    2014-03-01

    Exposure to contact allergens in order to produce allergic contact dermatitis (ACD) seems to induce hair cycle/growth, but the mechanism of this remains unclear. In the current study, we investigated this mechanism and found that repeated application of hapten induced production of interleukin (IL)-4 in lymph-node immune cells. In addition, hair growth was induced in mice after the adoptive transfer of T-helper (Th)2 cells that had been purified from mice exposed to repeated cutaneous application of hapten. These findings lead us to speculate that Th2 cells that are repeatedly hapten-sensitized are recruited to hapten-challenged skin areas, and thus stimulate the production of IL-4 in the vicinity of the hair follicles, which influences hair cycle/growth. Our results may provide fundamental insights into the mechanism of contact hypersensitivity-induced hair cycle/growth. © 2013 British Association of Dermatologists.

  10. The stat3/socs3a pathway is a key regulator of hair cell regeneration in zebrafish. [corrected].

    PubMed

    Liang, Jin; Wang, Dongmei; Renaud, Gabriel; Wolfsberg, Tyra G; Wilson, Alexander F; Burgess, Shawn M

    2012-08-01

    All nonmammalian vertebrates studied can regenerate inner ear mechanosensory receptors (i.e., hair cells) (Corwin and Cotanche, 1988; Lombarte et al., 1993; Baird et al., 1996), but mammals possess only a very limited capacity for regeneration after birth (Roberson and Rubel, 1994). As a result, mammals experience permanent deficiencies in hearing and balance once their inner ear hair cells are lost. The mechanisms of hair cell regeneration are poorly understood. Because the inner ear sensory epithelium is highly conserved in all vertebrates (Fritzsch et al., 2007), we chose to study hair cell regeneration mechanism in adult zebrafish, hoping the results would be transferrable to inducing hair cell regeneration in mammals. We defined the comprehensive network of genes involved in hair cell regeneration in the inner ear of adult zebrafish with the powerful transcriptional profiling technique digital gene expression, which leverages the power of next-generation sequencing ('t Hoen et al., 2008). We also identified a key pathway, stat3/socs3, and demonstrated its role in promoting hair cell regeneration through stem cell activation, cell division, and differentiation. In addition, transient pharmacological inhibition of stat3 signaling accelerated hair cell regeneration without overproducing cells. Taking other published datasets into account (Sano et al., 1999; Schebesta et al., 2006; Dierssen et al., 2008; Riehle et al., 2008; Zhu et al., 2008; Qin et al., 2009), we propose that the stat3/socs3 pathway is a key response in all tissue regeneration and thus an important therapeutic target for a broad application in tissue repair and injury healing.

  11. Mechanisms of Aminoglycoside-Induced Hair Cell Death

    ERIC Educational Resources Information Center

    Mangiardi, Dominic A.; Cotanche, Douglas A.

    2005-01-01

    Aminoglycoside antibiotics are commonly used because of their ability to treat bacterial infections, yet they also are a major cause of deafness. Aminoglycosides selectively damage the cochlea's sensory hair cells, the receptors that respond to the fluid movement in the cochlea to produce neural signals that are relayed to the brain. Sensory hair…

  12. Auditory Hair Cell Centrioles Undergo Confined Brownian Motion Throughout the Developmental Migration of the Kinocilium

    PubMed Central

    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 of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles’ confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. PMID:23823223

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

    PubMed

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

    2013-07-02

    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 of the kinocilium basal body (mother centriole) and its daughter centriole, which we analyzed using particle tracking and modeling. We found that both hair cell centrioles undergo confined Brownian movements around their equilibrium positions, under the apparent constraint of a radial restoring force of ∼0.1 pN. This magnitude depended little on centriole position, suggesting nonlinear interactions with constraining, presumably cytoskeletal elements. The only dynamic change observed during the period of kinocilium migration was a doubling of the centrioles' confinement area taking place early in the process. It emerges from these static and dynamic observations that kinocilia migrate gradually in parallel with the organization of hair cells into rows during cochlear neuroepithelium extension. Analysis of the confined motion of hair cell centrioles under normal and pathological conditions should help determine which structures contribute to the restoring force exerting on them. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Two passive mechanical conditions modulate power generation by the outer hair cells

    PubMed Central

    Gracewski, Sheryl M.

    2017-01-01

    In the mammalian cochlea, small vibrations of the sensory epithelium are amplified due to active electro-mechanical feedback of the outer hair cells. The level of amplification is greater in the base than in the apex of the cochlea. Theoretical studies have used longitudinally varying active feedback properties to reproduce the location-dependent amplification. The active feedback force has been considered to be proportional to the basilar membrane displacement or velocity. An underlying assumption was that organ of Corti mechanics are governed by rigid body kinematics. However, recent progress in vibration measurement techniques reveals that organ of Corti mechanics are too complicated to be fully represented with rigid body kinematics. In this study, two components of the active feedback are considered explicitly—organ of Corti mechanics, and outer hair cell electro-mechanics. Physiological properties for the outer hair cells were incorporated, such as the active force gain, mechano-transduction properties, and membrane RC time constant. Instead of a kinematical model, a fully deformable 3D finite element model was used. We show that the organ of Corti mechanics dictate the longitudinal trend of cochlear amplification. Specifically, our results suggest that two mechanical conditions are responsible for location-dependent cochlear amplification. First, the phase of the outer hair cell’s somatic force with respect to its elongation rate varies along the cochlear length. Second, the local stiffness of the organ of Corti complex felt by individual outer hair cells varies along the cochlear length. We describe how these two mechanical conditions result in greater amplification toward the base of the cochlea. PMID:28880884

  15. Otoacoustic Emissions in an Adult with Severe Hearing Loss.

    ERIC Educational Resources Information Center

    Prieve, Beth A.; And Others

    1991-01-01

    The paper describes the unexpected finding of evoked otoacoustic emissions from one ear of a subject with severe-to-profound bilateral sensorineural hearing loss. It is suggested that the subject may have a group of surviving outer hair cells in some regions of the left cochlea with corresponding inner hair cell or neural damage. (Author/DB)

  16. Factors associated with female pattern hair loss and its prevalence in Taiwanese women: a community-based survey.

    PubMed

    Su, Lin-Hui; Chen, Li-Sheng; Chen, Hsiu-Hsi

    2013-08-01

    Although female pattern hair loss (FPHL) has been considered simply the female counterpart of male pattern hair loss in men, the risk factors may differ. We sought to evaluate factors associated with FPHL and to estimate its prevalence in women. In total, 26,226 subjects aged 30 years and older participated in a cross-sectional survey. Ludwig and Norwood classifications were used to assess the degree of hair loss. Information on possible risk factors for FPHL was collected using a questionnaire interview. The prevalence of FPHL (Ludwig grade >I) for all ages was 11.8% (95% CI 11.5%-12.2%), increasing with advancing age. After controlling for age and family history, statistically significant associations were noted between FPHL and high fasting glucose (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.04-1.28), fewer childbirths (OR 1.24, 95% CI 1.12-1.38), breast-feeding (OR 0.88, 95% CI 0.78-0.98), oral contraceptive use (OR 1.21, 95% CI 1.01-1.45), and ultraviolet exposure more than 16 hours per week (OR 1.12, 95% CI 1.02-1.22). The validity and reliability of FPHL classification may be not perfect in this survey and may need to be verified. Information on family history may be still subject to recall bias. Risk factors for FPHL and male androgenic alopecia may differ. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

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

    NASA Technical Reports Server (NTRS)

    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 < 0.72) as well as neck width to cell body width (NBR < 0.64). The perforated patch variant of the whole-cell recording 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.

  18. Combover/CG10732, a Novel PCP Effector for Drosophila Wing Hair Formation

    PubMed Central

    Fagan, Jeremy K.; Dollar, Gretchen; Lu, Qiuheng; Barnett, Austen; Pechuan Jorge, Joaquin; Schlosser, Andreas; Pfleger, Cathie; Adler, Paul; Jenny, Andreas

    2014-01-01

    The polarization of cells is essential for the proper functioning of most organs. Planar Cell Polarity (PCP), the polarization within the plane of an epithelium, is perpendicular to apical-basal polarity and established by the non-canonical Wnt/Fz-PCP signaling pathway. Within each tissue, downstream PCP effectors link the signal to tissue specific readouts such as stereocilia orientation in the inner ear and hair follicle orientation in vertebrates or the polarization of ommatidia and wing hairs in Drosophila melanogaster. Specific PCP effectors in the wing such as Multiple wing hairs (Mwh) and Rho Kinase (Rok) are required to position the hair at the correct position and to prevent ectopic actin hairs. In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. Overexpression of Cmb causes the formation of a multiple hair cell phenotype (MHC), similar to loss of rok and mwh. This MHC phenotype is dominantly enhanced by removal of rok or of other members of the PCP effector gene family. Furthermore, we show that Cmb physically interacts with Mwh, and cmb null mutants suppress the MHC phenotype of mwh alleles. Our data indicate that Cmb is a novel PCP effector that promotes to wing hair formation, a function that is antagonized by Mwh. PMID:25207969

  19. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells

    PubMed Central

    Choi, Nahyun; Shin, Soyoung; Song, Sun U.; Sung, Jong-Hyuk

    2018-01-01

    Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal–regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration. PMID:29495622

  20. Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells.

    PubMed

    Choi, Nahyun; Shin, Soyoung; Song, Sun U; Sung, Jong-Hyuk

    2018-02-28

    Minoxidil directly promotes hair growth via the stimulation of dermal papilla (DP) and epithelial cells. Alternatively, there is little evidence for indirect promotion of hair growth via stimulation of adipose-derived stem cells (ASCs). We investigated whether minoxidil stimulates ASCs and if increased growth factor secretion by ASCs facilitates minoxidil-induced hair growth. Telogen-to-anagen induction was examined in mice. Cultured DP cells and vibrissae hair follicle organ cultures were used to further examine the underlying mechanisms. Subcutaneous injection of minoxidil-treated ASCs accelerated telogen-to-anagen transition in mice, and increased hair weight at day 14 post-injection. Minoxidil did not alter ASC proliferation, but increased migration and tube formation. Minoxidil also increased the secretion of growth factors from ASCs, including chemokine (C-X-C motif) ligand 1 (CXCL1), platelet-derived endothelial cell growth factor (PD-ECGF), and platelet-derived growth factor-C (PDGF-C). Minoxidil increased extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation, and concomitant upregulation of PD-ECGF and PDGF-C mRNA levels were attenuated by an ERK inhibitor. Subcutaneous injection of CXCL1, PD-ECGF, or PDGF-C enhanced anagen induction in mice, and both CXCL1 and PDGF-C increased hair length in ex vivo organ culture. Treatment with CXCL1, PD-ECGF, or PDGF-C also increased the proliferation index in DP cells. Finally, topical application of CXCL1, PD-ECGF, or PDGF-C with 2% minoxidil enhanced anagen induction when compared to minoxidil alone. Minoxidil stimulates ASC motility and increases paracrine growth factor signaling. Minoxidil-stimulated secretion of growth factors by ASCs may enhance hair growth by promoting DP proliferation. Therefore, minoxidil can be used as an ASC preconditioning agent for hair regeneration.

  1. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches

    PubMed Central

    Toyoshima, Koh-ei; Asakawa, Kyosuke; Ishibashi, Naoko; Toki, Hiroshi; Ogawa, Miho; Hasegawa, Tomoko; Irié, Tarou; Tachikawa, Tetsuhiko; Sato, Akio; Takeda, Akira; Tsuji, Takashi

    2012-01-01

    Organ replacement regenerative therapy is purported to enable the replacement of organs damaged by disease, injury or aging in the foreseeable future. Here we demonstrate fully functional hair organ regeneration via the intracutaneous transplantation of a bioengineered pelage and vibrissa follicle germ. The pelage and vibrissae are reconstituted with embryonic skin-derived cells and adult vibrissa stem cell region-derived cells, respectively. The bioengineered hair follicle develops the correct structures and forms proper connections with surrounding host tissues such as the epidermis, arrector pili muscle and nerve fibres. The bioengineered follicles also show restored hair cycles and piloerection through the rearrangement of follicular stem cells and their niches. This study thus reveals the potential applications of adult tissue-derived follicular stem cells as a bioengineered organ replacement therapy. PMID:22510689

  2. Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity.

    PubMed

    Holmes, William R; Huwe, Janice A; Williams, Barbara; Rowe, Michael H; Peterson, Ellengene H

    2017-05-01

    Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. J Neurophysiol 113: 2420-2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents. NEW & NOTEWORTHY Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed

  3. Treatment of female pattern hair loss.

    PubMed

    Hassani, Masoumeh; Gorouhi, Farzam; Babakoohi, Shahab; Moghadam-Kia, Siamak; Firooz, Alireza

    2012-01-01

    Female pattern hair loss (FPHL) as a distinctive entity was first described about 30 years ago. The objective of this study was to perform a systematic review of all randomized controlled trials for treatment of FPHL. A preliminary search was carried out in several databases up to August 2008 to identify all randomized controlled trials on nonsurgical interventions for treatment of FPHL. Studies reporting fewer than 10 patients and non-English articles were excluded. Additionally, references of relevant articles and reviews were checked manually in search for additional sources. Among 238 citations found in the preliminary search, 12 fulfilled all criteria to be included in the systematic review. Topical minoxidil 1% to 5% for 24 to 48 weeks was shown to be effective in FPHL and its effect was not related to age or androgen level of patients. In addition, it may be effective in women with FPHL, both with and without hyperandrogenism, and in young and old premenopausal or postmenopausal. In patients with increased serum androgens, oral flutamide but not finasteride or cyproterone acetate was more effective than no treatment. Topical minoxidil is effective in patients with FPHL, with or without hyperandrogenism, but there is limited evidence for the efficacy of antiandrogens.

  4. Contribution of hair density and hair diameter to the appearance and progression of androgenetic alopecia in Japanese men.

    PubMed

    Ishino, A; Takahashi, T; Suzuki, J; Nakazawa, Y; Iwabuchi, T; Tajima, M

    2014-11-01

    Androgenetic alopecia (AGA) is the most common type of baldness in men. The balding process is associated with the gradual miniaturization of hair follicles and successive hair loss. However, the relative contributions of hair density and diameter to AGA are still unclear. Hair density and hair diameter were investigated in Japanese men with or without AGA to elucidate the importance of these factors in the balding process. Male Japanese subjects with or without AGA (n = 369) were included in this study. Hair appearance at the vertex was evaluated by comparison with a series of standard photographs. Hair density was measured using a phototrichogram-based videomicroscopy technique, and hair diameter was assessed by comparison with a series of calibrated threads on the phototrichogram image. All subjects with AGA were ≥ 25 years of age. The mean percentage of thick hairs (> 80 μm) in all subjects with AGA was significantly lower than that in subjects without AGA aged ≥ 25 years (P < 0·01), but the mean percentage of vellus hairs (< 40 μm) in subjects with AGA was significantly higher (P < 0·001). By contrast, the mean density of the hair in all patients with AGA did not significantly differ from the density of those without AGA aged ≥ 25 years. However, the mean density of the hair in subjects without AGA aged < 25 years was significantly higher than that of both subjects without AGA aged ≥ 25 years (P < 0·001) and all subjects with AGA. Hair loss in men with AGA results mainly from the miniaturization of hair follicles rather than the loss of hair (shedding), at least for individuals who are ≥ 25 years of age and present with AGA. © 2014 British Association of Dermatologists.

  5. Foxp1 Regulates the Proliferation of Hair Follicle Stem Cells in Response to Oxidative Stress during Hair Cycling

    PubMed Central

    Zhao, Jianzhi; Li, Hanjun; Zhou, Rujiang; Ma, Gang; Dekker, Joseph D.; Tucker, Haley O.; Yao, Zhengju; Guo, Xizhi

    2015-01-01

    Hair follicle stem cells (HFSCs) in the bugle circularly generate outer root sheath (ORS) through linear proliferation within limited cycles during anagen phases. However, the mechanisms controlling the pace of HFSC proliferation remain unclear. Here we revealed that Foxp1, a transcriptional factor, was dynamically relocated from the nucleus to the cytoplasm of HFSCs in phase transitions from anagen to catagen, coupled with the rise of oxidative stress. Mass spectrum analyses revealed that the S468 phosphorylation of Foxp1 protein was responsive to oxidative stress and affected its nucleocytoplasmic translocation. Foxp1 deficiency in hair follicles led to compromised ROS accrual and increased HFSC proliferation. And more, NAC treatment profoundly elongated the anagen duration and HFSC proliferation in Foxp1-deficient background. Molecularly, Foxp1 augmented ROS levels through suppression of Trx1-mediated reductive function, thereafter imposing the cell cycle arrest by modulating the activity of p19/p53 pathway. Our findings identify a novel role for Foxp1 in controlling HFSC proliferation with cellular dynamic location in response to oxidative stress during hair cycling. PMID:26171970

  6. Peroxynitrite induces apoptosis of mouse cochlear hair cells via a Caspase-independent pathway in vitro.

    PubMed

    Cao, Zhixin; Yang, Qianqian; Yin, Haiyan; Qi, Qi; Li, Hongrui; Sun, Gaoying; Wang, Hongliang; Liu, Wenwen; Li, Jianfeng

    2017-11-01

    Peroxynitrite (ONOO - ) is a potent and versatile oxidant implicated in a number of pathophysiological processes. The present study was designed to investigate the effect of ONOO - on the cultured cochlear hair cells (HCs) of C57BL/6 mice in vitro as well as the possible mechanism underlying the action of such an oxidative stress. The in vitro primary cultured cochlear HCs were subjected to different concentrations of ONOO - , then, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy (TEM), the apoptosis was determined by Terminal deoxynucleotidyl transferase dUNT nick end labeling (TUNEL) assay, the mRNA expressions of Caspase-3, Caspase-8, Caspase-9, Apaf1, Bcl-2, and Bax were analyzed by RT-PCR, and the protein expressions of Caspase-3 and AIF were assessed by immunofluorescence. This work demonstrated that direct exposure of primary cultured cochlear HCs to ONOO - could result in a base-to-apex gradient injury of HCs in a concentration-dependent manner. Furthermore, ONOO - led to much more losses of outer hair cells than inner hair cells mainly through the induction of apoptosis of HCs as evidenced by TEM and TUNEL assays. The mRNA expressions of Caspase-8, Caspase-9, Apaf1, and Bax were increased and, meanwhile, the mRNA expression of Bcl-2 was decreased in response to ONOO - treatment. Of interesting, the expression of Caspase-3 had no significant change, whereas, the expression alteration of AIF was observed. These results suggested that ONOO - can effectively damage the survival of cochlear HCs via triggering the apoptotic pathway. The findings from this work suggest that ONOO - -induced apoptosis is mediated, at least in part, via a Caspase-independent pathway in cochlear HCs.

  7. Functional support of glutamate as a vestibular hair cell transmitter in an amniote

    NASA Technical Reports Server (NTRS)

    Cochran, S. L.; Correia, M. J.

    1995-01-01

    Although hair cells in the cochlea and in the vestibular endorgans of anamniotes are thought to release glutamate or a similar compound as their transmitter, there is little evidence in amniotes (which, unlike anamniotes, possess both type I and II hair cells) as to the nature of the hair cell transmitters in the vestibular labyrinth. We have recorded extracellularly from single semicircular canal afferents in the turtle labyrinth maintained in vitro and have bath-applied a number of transmitter agonists and antagonists to relate the effects of these substances to the actions of the endogenous transmitter substances. Both glutamate and aspartate strongly excite the afferents while GABA and carbachol have negligible or weak effects. In contrast to its lack of effect on afferent activity in some anamniotes, N-methyl-D-aspartate (NMDA) was also found to excite these afferents. Kynurenic acid reversibly reduced the resting firing rates of the afferents and the increases in firing due to the application of glutamate and aspartate. These findings provide preliminary support for the hypothesis that glutamate (or a related compound) is also a vestibular hair cell transmitter in amniotes.

  8. The hair follicle enigma.

    PubMed

    Bernard, Bruno A

    2017-06-01

    The hair follicle is a mini-organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome-mediated cell-cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. 15-deoxy prostaglandin J2, the nonenzymatic metabolite of prostaglandin D2, induces apoptosis in keratinocytes of human hair follicles: a possible explanation for prostaglandin D2-mediated inhibition of hair growth.

    PubMed

    Joo, Hyun Woo; Kang, Yoo Ri; Kwack, Mi Hee; Sung, Young Kwan

    2016-07-01

    Recent studies have shown that prostaglandin D2 (PGD2) and its nonenzymatic metabolite, 15-deoxy-Δ(12,14)-prostaglandin J2 (15-dPGJ2), inhibit in vitro growth of explanted human hair follicles and inhibit hair growth in mice through the GPR44 (DP2). However, the underlying mechanism is still unclear. In this study, we first investigated the expression of DP2 in human hair follicles and in cultured follicular cells. We found that DP2 is strongly expressed in the outer root sheath (ORS) cells and weakly expressed in the dermal papilla (DP) cells. We observed slight growth stimulation when ORS and DP cells were treated with PGD2. We also observed slight growth stimulation when DP and ORS cells were treated with low concentrations (0.5 and 1 μM) of 15-dPGJ2. However, 5 μM 15-dPGJ2 inhibited the viability and caused apoptosis of both cell types. Exposure of cultured human hair follicles to 15-dPGJ2 resulted in significant apoptosis in follicular keratinocytes. Altogether, our data provide an evidence that 15-dPGJ2 promotes apoptosis in follicular keratinocytes and provide rationale for developing remedies for the prevention and treatment of hair loss based on DP2 antagonism.

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Mechano-electrical transduction currents in isolated vestibular hair cells of the chick.

    PubMed

    Ohmori, H

    1985-02-01

    Properties of a mechano-electrical transduction channel were studied in enzymatically dissociated chick vestibular hair cells by using a whole-cell recording variation of the patch voltage-clamp technique. The apical hair bundle was stimulated by a glass rod which moved along a one-dimensional axis when stimulated by either a triangular or a trapezoidal command voltage. The motion of the glass rod was monitored optically using a photodiode. In response to triangular stimuli, the hair cell generated a current of triangular wave form with occasional step-like spiky or zigzag-appearing events. Control experiments confirmed that the current was generated only when the hair bundle was displaced towards the tallest stereocilium. The mechano-sensitive current was blocked by streptomycin and by neomycin. The blockage by streptomycin was clearly voltage dependent: the reduction of the current became larger with hyperpolarization of the membrane. This suggests that the positively charged antibiotic molecules plug the mechanically gated channels. From the evidence presented in 3 and 4 above, the mechano-sensitive current recorded here was identified as the mechano-electrical transduction (m-e.t.) current. The permeability of the m-e.t. channel to various monovalent cations was determined from reversal potential measurements. Since a CsCl-EGTA intracellular medium was used, all the permeabilities were calculated relative to PCs. The sequence of permeabilities was Li greater than Na greater than or equal to K greater than or equal to Rb greater than Cs greater than choline greater than TMA greater than TEA. External Ca ions were indispensable for the recording of transduction current and Sr ions could replace Ca ions without loss of the transduction activity. The minimum [Ca]o for stable generation of the m-e.t. current was 20 microM in Cs saline. The addition of 50-200 microM-Ca to the isotonic Ba saline could maintain the m-e.t. current. The m-e.t. current was observed in

  12. Organ-level quorum sensing directs regeneration in hair stem cell populations

    PubMed Central

    Chen, Chih-Chiang; Wang, Lei; Plikus, Maksim V.; Jiang, Ting Xin; Murray, Philip J.; Ramos, Raul; Guerrero-Juarez, Christian F.; Hughes, Michael W; Lee, Oscar K.; Shi, Songtao; Widelitz, Randall B.; Lander, Arthur D.; Chuong, Cheng Ming

    2015-01-01

    SUMMARY Coordinated organ behavior is crucial for an effective response to environmental stimuli. By studying regeneration of hair follicles in response to patterned hair removal, we demonstrate that organ-level quorum sensing allows coordinated responses to skin injury. Removing hair at different densities leads to a regeneration of up to 5 times more neighboring, unplucked resting hairs, indicating activation of a collective decision-making process. Through data modeling, the range of the quorum signal was estimated to be on the order of 1 mm, greater than expected for a diffusible molecular cue. Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α secreting macrophages, which accumulate and signal to both plucked and unplucked follicles. By coupling immune response with regeneration, this mechanism allows skin to respond predictively to distress, disregarding mild injury, while meeting stronger injury with full-scale cooperative activation of stem cells. PMID:25860610

  13. Diguanoside tetraphosphate (Gp₄G) is an epithelial cell and hair growth regulator.

    PubMed

    Severino, Divinomar; Zorn, Telma M T; Micke, Gustavo A; Costa, Ana C O; Silva, José Roberto M C; Nogueira, Leandro F; Kowaltowski, Alicia J; Kowaltowski, Alica J; Baptista, Maurício S

    2011-01-01

    Our goal was to study the effect of Gp₄G on skin tissues and unravel its intracellular action mechanisms. The effects of Gp₄G formulation, a liposomic solution of Artemia salina extract, on several epidermal, depmal, and hair follicle structures were quantified. A 50% increase in hair length and a 30% increase in the number of papilla cells were explained by the changes in the telogen/anagen hair follicle phases. Increasing skin blood vessels and fibroblast activation modified collagen arrangement in dermal tissues. Imunohistochemical staining revealed expressive increases of versican (VER) deposition in the treated animals (68%). Hela and fibroblast cells were used as in vitro models. Gp₄G enters both cell lines, with a hyperbolic saturation profile inducing an increase in the viabilities of Hela and fibroblast cells. Intracellular ATP and other nucleotides were quantified in Hela cells showing a 38% increase in intracellular ATP concentration and increases in the intracellular concentration of tri- , di- , and monophosphate nucleosides, changing the usual quasi-equilibrium state of nucleotide concentrations. We propose that this change in nucleotide equilibrium affects several biochemical pathways and explains the cell and tissue activations observed experimentally.

  14. Expression and localization of VEGFR-2 in hair follicles during induced hair growth in mice.

    PubMed

    Wu, Xian-Jie; Jing, Jing; Lu, Zhong-Fa; Zheng, Min

    2018-06-16

    Recently, VEGFR-2 has been detected not only in vascular and lymphatic endothelial cells but also in some non-vascular endothelial cells, particularly human hair follicles, sebaceous glands, and sweat glands. In addition, VEGFR-2 has been confirmed to play direct roles in hair follicle keratinocyte regulation beyond simply angiogenesis. To elucidate whether VEGFR-2 activation plays a role in hair follicle cycling regulation, immunofluorescence of VEGFR-2 expression was performed during hair cycling of the dorsum of the mouse induced by hair plucking. We observed that staining for VEGFR-2 in hair follicles during anagen II and IV was much stronger than during anagen VI, catagen and telogen. During anagen II, intense staining for VEGFR-2 was observed on the keratinocyte strands of the hair follicle. Subsequently, we detected intense staining for VEGFR-2 in the ORS, IRS and hair bulb during anagen IV. Moderate staining for VEGFR-2 was detected in the ORS and hair bulb, but staining was most intense in IRS during anagen VI. During catagen, staining for VEGFR-2 in the IRS remained intense, while staining in the ORS and hair bulb was significantly weakened and was negative in the dermal papilla. During telogen, we detected VEGFR-2 in germ cells, cap, and club hair adjoining the epidermis. In conclusion, VEGFR-2 was expressed on the hair follicles of the dorsum of the mouse and varied in expression on the mouse hair follicles during hair cycling, suggesting that VEGFR-2 may exert roles in hair cycle regulation in hair follicles on the dorsum of mice.

  15. [Experimental study on Dendrobium candidum polysaccharides on promotion of hair growth].

    PubMed

    Chen, Jian; Qi, Hui; Li, Jin-Biao; Yi, Yan-Qun; Chen, Dan; Hu, Xiao-Hong; Wang, Mei-Ling; Sun, Xing-Li; Wei, Xiao-Yong

    2014-01-01

    To observe the effect and mechanism of Dendrobium candidum polysaccharides (DCP) in promoting hair growth, in order to lay a foundation for the development and utilization of D. candidum. The water-extraction and alcohol-precipitation method was adopted to extract DCP, and the phenol-sulphuric acid method was used to determine its content. Thirty C57BL6J mice were collected to establish the hair loss model with hair removal cream. They were randomly divided into the control group, the positive control group and the DCP group, and given 0.2 mL of ultra-pure water, minoxidil tincture and DCP (5.0 g x L(-1)) 21 days. The mice hair growth scoring standard was adopted to evaluate the hair growth of C57BL/6J mice at 7, 14 d. The hairs in unit hair-losing areas of treated C57BL/6J mice at 21 d were weighed to evaluate the effect of DCP on the promotion of hair growth. MTT assay and RT-PCR method were used to evaluate the effect of DCP on the proliferatin of HaCaT cells and the mRNA expression of VEGF in HaCaT cells. The extraction percent of DCP was 29.87%, and its content was 79.65%. The average scores for the hair growth and weight of C57BL/6J mice of DCP group were much higher than the control group. The survival rate and mRNA expression of VEGF of HaCaT cells were much higher than the control group. DCP has the effect in promoting hair growth. Its mechanism may be related to the up-regulation of the mRNA expression of VEGF.

  16. Role for a Novel Usher Protein Complex in Hair Cell Synaptic Maturation

    PubMed Central

    Zallocchi, Marisa; Meehan, Daniel T.; Delimont, Duane; Rutledge, Joseph; Gratton, Michael Anne; Flannery, John; Cosgrove, Dominic

    2012-01-01

    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 waltzerav3J 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. PMID:22363448

  17. The treatment of female pattern hair loss and other applications of surgical hair restoration in women.

    PubMed

    Epstein, Jeffrey S

    2004-05-01

    In the specialty of surgical hair restoration, men comprise more than 90% of the patients treated; however, in the last few years the number of women undergoing the procedure has increased significantly. The reasons for this growth are many and include the increase in public awareness of the efficacy of hair transplantation from such sources as the media,the Internet, advertising and word of mouth. More importantly, advances in technique have significantly improved results, increasing the confidence level in women to undergo the procedure and in hair transplant specialists to offer it.

  18. LOSS OF SESTRIN 2 POTENTIATES THE EARLY ONSET OF AGE-RELATED SENSORY CELL DEGENERATION IN THE COCHLEA

    PubMed Central

    ZHANG, CELIA; SUN, WEI; LI, JI; XIONG, BINBIN; FRYE, MITCHELL D.; DING, DALIAN; SALVI, RICHARD; KIM, MI-JUNG; SOMEYA, SHINICHI; HU, BO HUA

    2017-01-01

    Sestrin 2 (SESN2) is a stress-inducible protein that protects tissues from oxidative stress and delays the aging process. However, its role in maintaining the functional and structural integrity of the cochlea is largely unknown. Here, we report the expression of SESN2 protein in the sensory epithelium, particularly in hair cells. Using C57BL/6J mice, a mouse model of age-related cochlear degeneration, we observed a significant age-related reduction in SESN2 expression in cochlear tissues that was associated with early onset hearing loss and accelerated age-related sensory cell degeneration that progressed from the base toward the apex of the cochlea. Hair cell death occurred by caspase-8 mediated apoptosis. Compared to C57BL/6J control mice, Sesn2 KO mice displayed enhanced expression of proinflammatory genes and activation of basilar membrane macrophages, suggesting that loss of SESN2 function provokes the immune response. Together, these results suggest that Sesn2 plays an important role in cochlear homeostasis and immune responses to stress. PMID:28818524

  19. Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging

    NASA Astrophysics Data System (ADS)

    Zholudeva, Lyandysha V.; Ward, Kristina G.; Nichols, Michael G.; Smith, Heather Jensen

    2015-05-01

    Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs.

  20. Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging

    PubMed Central

    Zholudeva, Lyandysha V.; Ward, Kristina G.; Nichols, Michael G.; Smith, Heather Jensen

    2015-01-01

    Abstract. Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs. PMID:25688541

  1. Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea

    PubMed Central

    Chen, Yan; Lu, Xiaoling; Guo, Luo; Ni, Wenli; Zhang, Yanping; Zhao, Liping; Wu, Lingjie; Sun, Shan; Zhang, Shasha; Tang, Mingliang; Li, Wenyan; Chai, Renjie; Li, Huawei

    2017-01-01

    Hair cell (HC) loss is the major cause of permanent sensorineural hearing loss in mammals. Unlike lower vertebrates, mammalian cochlear HCs cannot regenerate spontaneously after damage, although the vestibular system does maintain limited HC regeneration capacity. Thus HC regeneration from the damaged sensory epithelium has been one of the main areas of research in the field of hearing restoration. Hedgehog signaling plays important roles during the embryonic development of the inner ear, and it is involved in progenitor cell proliferation and differentiation as well as the cell fate decision. In this study, we show that recombinant Sonic Hedgehog (Shh) protein effectively promotes sphere formation, proliferation, and differentiation of Lgr5+ progenitor cells isolated from the neonatal mouse cochlea. To further explore this, we determined the effect of Hedgehog signaling on cell proliferation and HC regeneration in cultured cochlear explant from transgenic R26-SmoM2 mice that constitutively activate Hedgehog signaling in the supporting cells of the cochlea. Without neomycin treatment, up-regulation of Hedgehog signaling did not significantly promote cell proliferation or new HC formation. However, after injury to the sensory epithelium by neomycin treatment, the over-activation of Hedgehog signaling led to significant supporting cell proliferation and HC regeneration in the cochlear epithelium explants. RNA sequencing and real-time PCR were used to compare the transcripts of the cochleae from control mice and R26-SmoM2 mice, and multiple genes involved in the proliferation and differentiation processes were identified. This study has important implications for the treatment of sensorineural hearing loss by manipulating the Hedgehog signaling pathway. PMID:29311816

  2. Efficacy and Safety of Once-Daily Minoxidil Foam 5% Versus Twice-Daily Minoxidil Solution 2% in Female Pattern Hair Loss: A Phase III, Randomized, Investigator-Blinded Study.

    PubMed

    Blume-Peytavi, Ulrike; Shapiro, Jerry; Messenger, Andrew G; Hordinsky, Maria K; Zhang, Paul; Quiza, Carlos; Doshi, Uday; Olsen, Elise A

    2016-07-01

    A once-daily minoxidil topical foam (MTF) has been developed to treat female pattern hair loss.
    Determine noninferiority of once-daily 5% MTF versus twice-daily 2% minoxidil topical solution (MTS) based on the change from baseline in target area hair count (TAHC) at 24 weeks. In a randomized, phase III trial, women with female pattern hair loss received once-daily 5% MTF (n=161) or twice-daily 2% MTS (n=161) for 52 weeks. Primary endpoint was change from baseline in TAHC at 24 weeks. Secondary endpoint was change from baseline in TAHC at 12 weeks. Exploratory endpoints included change in total unit area density and change in overall scalp coverage.
    Once-daily 5% MTF increased TAHC from baseline (adjusted mean ± standard error) by 23.9 ± 2.1 hairs/cm2 at week 24. Twice-daily 2% MTS increased TAHC 24.2 ± 2.1 hairs/cm2 at week 24. The treatment difference was -0.3 hairs/cm2 (95% CI = -6.0, 5.4). Since the lower bound of the 95% CI was less than -5.0, the prespecified noninferiority goal was not met. Both treatments were well tolerated.
    Once-daily 5% MTF and twice-daily 2% MTS induced hair regrowth in female pattern hair loss, but prespecified noninferiority criteria were not met.
    ClinicalTrials.gov identifier: NCT01145625

    J Drugs Dermatol. 2016;15(7):883-889.

  3. Alterations in Hair Follicle Dynamics in Women

    PubMed Central

    Piérard-Franchimont, Claudine; Piérard, Gérald E.

    2013-01-01

    Endocrine changes supervening after parturition and menopause participate in the control of sebum production and hair growth modulation. The ensuing conditions include some peculiar aspects of hair loss (effluvium), alopecia, and facial hirsutism. The hair cycling is of major clinical relevance because most hair growth disorders result from disturbances in this chronobiological feature. Of note, any correlation between a biologic abnormality and hair cycling disturbance does not prove a relationship of causality. The proportion of postmenopausal women is rising in the overall population. Therefore, the prevalence of these hair follicle disturbances is globally on the rise. Current therapies aim at correcting the underlying hormonal imbalances, and at improving the overall cosmetic appearance. However, in absence of pathogenic diagnosis and causality criteria, chances are low that a treatment given by the whims of fate will adequately control hair effluvium. The risk and frequency of therapeutic inertia are further increased. When the hair loss is not controlled and/or compensated by growth of new hairs, several clinical aspects of alopecia inexorably develop. Currently, there is little evidence supporting any specific treatment for these endocrine hair disorders in post-partum and postmenopausal women. Current hair treatment strategies are symptomatic and nonspecific so current researchers aim at developing new, targeted methods. PMID:24455742

  4. Alterations in hair follicle dynamics in women.

    PubMed

    Piérard-Franchimont, Claudine; Piérard, Gérald E

    2013-01-01

    Endocrine changes supervening after parturition and menopause participate in the control of sebum production and hair growth modulation. The ensuing conditions include some peculiar aspects of hair loss (effluvium), alopecia, and facial hirsutism. The hair cycling is of major clinical relevance because most hair growth disorders result from disturbances in this chronobiological feature. Of note, any correlation between a biologic abnormality and hair cycling disturbance does not prove a relationship of causality. The proportion of postmenopausal women is rising in the overall population. Therefore, the prevalence of these hair follicle disturbances is globally on the rise. Current therapies aim at correcting the underlying hormonal imbalances, and at improving the overall cosmetic appearance. However, in absence of pathogenic diagnosis and causality criteria, chances are low that a treatment given by the whims of fate will adequately control hair effluvium. The risk and frequency of therapeutic inertia are further increased. When the hair loss is not controlled and/or compensated by growth of new hairs, several clinical aspects of alopecia inexorably develop. Currently, there is little evidence supporting any specific treatment for these endocrine hair disorders in post-partum and postmenopausal women. Current hair treatment strategies are symptomatic and nonspecific so current researchers aim at developing new, targeted methods.

  5. Ecklonia cava promotes hair growth.

    PubMed

    Bak, S S; Ahn, B N; Kim, J A; Shin, S H; Kim, J C; Kim, M K; Sung, Y K; Kim, S K

    2013-12-01

    Previous studies have reported the protective effects on skin elasticity of the edible marine seaweed Ecklonia cava, which acts through regulation of both antioxidative and anti-inflammatory responses. We evaluated the effect of E. cava and one of its components, dioxinodehydroeckol, on hair-shaft growth in cultured human hair follicles and on hair growth in mice. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to check cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells after treatment with E. cava and its metabolite, dioxinodehydroeckol. Hair-shaft growth was measured using the in vitro hair-follicle organ-culture system, in the presence or absence of E. cava and dioxinodehydroeckol. Anagen induction activity was examined by topical application of E. cava to the dorsal skin of C57BL/6 mice. Insulin-like growth factor (IGF)-1 expression was measured by reverse transcriptase PCR and ELISA. The proliferation activity was found to be highest for the ethyl acetate-soluble fraction of E. cava (EAFE) in DPCs and in ORS cells. Treatment with EAFE resulted in elongation of the hair shaft in cultured human hair follicles, and promoted transition of the hair cycle from the telogen to the anagen phase in the dorsal skin of C57BL/6 mice. In addition, EAFE induced an increase in IGF-1 expression in DPCs. Dioxinodehydroeckol, a component of E. cava, induced elongation of the hair shaft, an increase in proliferation of DPCs and ORS cells, and an increase in expression of IGF-1 in DPCs. These results suggest that E. cava containing dioxinodehydroeckol promotes hair growth through stimulation of DPCs and ORS cells. © 2013 British Association of Dermatologists.

  6. Noise-Induced Hearing Loss (NIHL).

    ERIC Educational Resources Information Center

    Seidman, Michael D.

    1999-01-01

    This article provides an overview of noise-induced hearing loss (NIHL), the leading cause of occupationally induced hearing loss in industrialized countries. It discusses causes of NIHL and compelling evidence that reactive oxygen metabolites and cochlear hypoprefusion are responsible for the destruction of cochlear hair cells. Prevention is also…

  7. The structure and organization of lanceolate mechanosensory complexes at mouse hair follicles

    PubMed Central

    Li, Lishi; Ginty, David D

    2014-01-01

    In mouse hairy skin, lanceolate complexes associated with three types of hair follicles, guard, awl/auchene and zigzag, serve as mechanosensory end organs. These structures are formed by unique combinations of low-threshold mechanoreceptors (LTMRs), Aβ RA-LTMRs, Aδ-LTMRs, and C-LTMRs, and their associated terminal Schwann cells (TSCs). In this study, we investigated the organization, ultrastructure, and maintenance of longitudinal lanceolate complexes at each hair follicle subtype. We found that TSC processes at hair follicles are tiled and that individual TSCs host axonal endings of more than one LTMR subtype. Electron microscopic analyses revealed unique ultrastructural features of lanceolate complexes that are proposed to underlie mechanotransduction. Moreover, Schwann cell ablation leads to loss of LTMR terminals at hair follicles while, in contrast, TSCs remain associated with hair follicles following skin denervation in adult mice and, remarkably, become re-associated with newly formed axons, indicating a TSC-dependence of lanceolate complex maintenance and regeneration in adults. DOI: http://dx.doi.org/10.7554/eLife.01901.001 PMID:24569481

  8. The structure and organization of lanceolate mechanosensory complexes at mouse hair follicles.

    PubMed

    Li, Lishi; Ginty, David D

    2014-02-25

    In mouse hairy skin, lanceolate complexes associated with three types of hair follicles, guard, awl/auchene and zigzag, serve as mechanosensory end organs. These structures are formed by unique combinations of low-threshold mechanoreceptors (LTMRs), Aβ RA-LTMRs, Aδ-LTMRs, and C-LTMRs, and their associated terminal Schwann cells (TSCs). In this study, we investigated the organization, ultrastructure, and maintenance of longitudinal lanceolate complexes at each hair follicle subtype. We found that TSC processes at hair follicles are tiled and that individual TSCs host axonal endings of more than one LTMR subtype. Electron microscopic analyses revealed unique ultrastructural features of lanceolate complexes that are proposed to underlie mechanotransduction. Moreover, Schwann cell ablation leads to loss of LTMR terminals at hair follicles while, in contrast, TSCs remain associated with hair follicles following skin denervation in adult mice and, remarkably, become re-associated with newly formed axons, indicating a TSC-dependence of lanceolate complex maintenance and regeneration in adults. DOI: http://dx.doi.org/10.7554/eLife.01901.001.

  9. Healthy hair: what is it?

    PubMed

    Sinclair, Rodney D

    2007-12-01

    Shiny hair with a smooth texture and clean-cut ends or tapered tips is generally perceived to be healthy. Hair texture and shine relate to hair surface properties, whereas the integrity of hair ends relates to the hair cortex. Hair can be straight, wavy or curly, blonde, black, brown, red, gray white, and its natural variations are important to our identity. Manipulation of the normal structure of the hair shaft is epidemic and dictated by culture, fashion, and above all, celebrity. Although cosmetic procedures are intrinsically safe, there is potential for damage to the hair. Loss of lustre, frizz, split ends, and other hair problems are particularly prevalent among people who repeatedly alter the natural style of their hair or among people with hair that is intrinsically weak. This may be due to individual or racial variation or less commonly an inherited structural abnormality in hair fiber formation. Hair health is also affected by common afflictions of the scalp as well as age-related phenomena such as graying and androgenetic alopecia. Hair products that improve the structural integrity of hair fibers and increase tensile strength are available, as are products that increase hair volume, reduce frizz, improve hair manageability, and stimulate new hair growth.

  10. Noninvasive method for assessing the human circadian clock using hair follicle cells

    PubMed Central

    Akashi, Makoto; Soma, Haruhiko; Yamamoto, Takuro; Tsugitomi, Asuka; Yamashita, Shiko; Yamamoto, Takuya; Nishida, Eisuke; Yasuda, Akio; Liao, James K.; Node, Koichi

    2010-01-01

    A thorough understanding of the circadian clock requires qualitative evaluation of circadian clock gene expression. Thus far, no simple and effective method for detecting human clock gene expression has become available. This limitation has greatly hampered our understanding of human circadian rhythm. Here we report a convenient, reliable, and less invasive method for detecting human clock gene expression using biopsy samples of hair follicle cells from the head or chin. We show that the circadian phase of clock gene expression in hair follicle cells accurately reflects that of individual behavioral rhythms, demonstrating that this strategy is appropriate for evaluating the human peripheral circadian clock. Furthermore, using this method, we indicate that rotating shift workers suffer from a serious time lag between circadian gene expression rhythms and lifestyle. Qualitative evaluation of clock gene expression in hair follicle cells, therefore, may be an effective approach for studying the human circadian clock in the clinical setting. PMID:20798039

  11. ABA Suppresses Root Hair Growth via the OBP4 Transcriptional Regulator1[OPEN

    PubMed Central

    Kawamura, Ayako; Schäfer, Sabine; Breuer, Christian; Shibata, Michitaro; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Matsui, Minami

    2017-01-01

    Plants modify organ growth and tune morphogenesis in response to various endogenous and environmental cues. At the cellular level, organ growth is often adjusted by alterations in cell growth, but the molecular mechanisms underlying this control remain poorly understood. In this study, we identify the DNA BINDING WITH ONE FINGER (DOF)-type transcription regulator OBF BINDING PROTEIN4 (OBP4) as a repressor of cell growth. Ectopic expression of OBP4 in Arabidopsis (Arabidopsis thaliana) inhibits cell growth, resulting in severe dwarfism and the repression of genes involved in the regulation of water transport, root hair development, and stress responses. Among the basic helix-loop-helix transcription factors known to control root hair growth, OBP4 binds the ROOT HAIR DEFECTIVE6-LIKE2 (RSL2) promoter to repress its expression. The accumulation of OBP4 proteins is detected in expanding root epidermal cells, and its expression level is increased by the application of abscisic acid (ABA) at concentrations sufficient to inhibit root hair growth. ABA-dependent induction of OBP4 is associated with the reduced expression of RSL2. Furthermore, ectopic expression of OBP4 or loss of RSL2 function results in ABA-insensitive root hair growth. Taken together, our results suggest that OBP4-mediated transcriptional repression of RSL2 contributes to the ABA-dependent inhibition of root hair growth in Arabidopsis. PMID:28167701

  12. The structural and functional differentiation of hair cells in a lizard’s basilar papilla suggests an operational principle of amniote cochleas

    PubMed Central

    Chiappe, M. Eugenia; Kozlov, Andrei S.; Hudspeth, A. J.

    2007-01-01

    The hair cells in the mammalian cochlea are of two distinct types. Inner hair cells are responsible for transducing mechanical stimuli into electrical responses, which they forward to the brain through a copious afferent innervation. Outer hair cells, which are thought to mediate the active process that sensitizes and tunes the cochlea, possess a negligible afferent innervation. For every inner hair cell there are approximately three outer hair cells, so only a quarter of the hair cells directly deliver information to the central nervous system. Although this is a surprising feature for a sensory system, the occurrence of a similar innervation pattern in birds and crocodilians suggests that the arrangement has an adaptive value. Using a lizard with highly developed hearing, the tokay gecko, we demonstrate in the present study that the same principle operates in a third major group of terrestrial animals. We propose that the differentiation of hair cells into signaling and amplifying classes reflects incompatible strategies for the optimization of mechanoelectrical transduction and of an active process based on active hair-bundle motility. PMID:17978038

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

    PubMed Central

    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

  14. The function and molecular identity of inward rectifier channels in vestibular hair cells of the mouse inner ear

    PubMed Central

    Levin, Michaela E.

    2012-01-01

    Inner ear hair cells respond to mechanical stimuli with graded receptor potentials. These graded responses are modulated by a host of voltage-dependent currents that flow across the basolateral membrane. Here, we examine the molecular identity and the function of a class of voltage-dependent ion channels that carries the potassium-selective inward rectifier current known as IK1. IK1 has been identified in vestibular hair cells of various species, but its molecular composition and functional contributions remain obscure. We used quantitative RT-PCR to show that the inward rectifier gene, Kir2.1, is highly expressed in mouse utricle between embryonic day 15 and adulthood. We confirmed Kir2.1 protein expression in hair cells by immunolocalization. To examine the molecular composition of IK1, we recorded voltage-dependent currents from type II hair cells in response to 50-ms steps from −124 to −54 in 10-mV increments. Wild-type cells had rapidly activating inward currents with reversal potentials close to the K+ equilibrium potential and a whole-cell conductance of 4.8 ± 1.5 nS (n = 46). In utricle hair cells from Kir2.1-deficient (Kir2.1−/−) mice, IK1 was absent at all stages examined. To identify the functional contribution of Kir2.1, we recorded membrane responses in current-clamp mode. Hair cells from Kir2.1−/− mice had significantly (P < 0.001) more depolarized resting potentials and larger, slower membrane responses than those of wild-type cells. These data suggest that Kir2.1 is required for IK1 in type II utricle hair cells and contributes to hyperpolarized resting potentials and fast, small amplitude receptor potentials in response to current inputs, such as those evoked by hair bundle deflections. PMID:22496522

  15. Blocking caspase-3-dependent pathway preserves hair cells from salicylate-induced apoptosis in the guinea pig cochlea.

    PubMed

    Feng, Hao; Yin, Shi-Hua; Tang, An-Zhou

    2011-07-01

    In the present study, we aim to explore whether the caspase-3-dependent pathway is involved in the apoptotic cell death that occurs in the hair cells (HCs) of guinea pig cochlea following a salicylate treatment. Guinea pigs received sodium salicylate (Na-SA), at a dose of 200 mg·kg(-1)·d(-1) i.p., as a vehicle for 5 consecutive days. In some experiments, N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (zDEVD-FMK), a specific apoptosis inhibitor, was directly applied into the cochlea via the round window niche (RWN) prior to salicylate treatment for determination of caspase-3 activation. Alterations in auditory function were evaluated with auditory brainstem responses (ABR) thresholds. Caspase-3 activity was determined by measuring the proteolytic cleavage product of caspase-3 (N-terminated peptide substrate). DNA fragmentation within the nuclei was examined with a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Ultrastructure variation in the target cell was assessed by electron microscopy (EM). Salicylate treatment initiated an obvious elevation in ABR thresholds with a maximum average shift of 60 dB sound pressure level (SPL), and caused significant apoptosis in both inner (IHCs) and outer (OHCs) hair cells resulted from an evident increasing in immunoreactivity to caspase-3 protease. Transmission electron microscopy (TEM) displayed chromatin condensation and nucleus margination accompanied by cell body shrinkage in the OHCs, but not in the IHCs. Scanning electron microscopy (SEM) showed breakdown, fusion, and loss in the stereociliary bundles at the apex of OHCs rather than IHCs. zDEVD-FMK pretreatment prior to salicylate injection substantially attenuated an expression of the apoptotic protease and protected HCs against apoptotic death, followed by a moderate relief in the thresholds of ABR, an alleviation in the submicroscopic structure was also identified. In particular, disorientation and insertion in the

  16. Chronic restraint stress inhibits hair growth via substance P mediated by reactive oxygen species in mice.

    PubMed

    Liu, Nan; Wang, Lin-Hui; Guo, Ling-Ling; Wang, Guo-Qing; Zhou, Xi-Ping; Jiang, Yan; Shang, Jing; Murao, Koji; Chen, Jing-Wei; Fu, Wen-Qing; Zhang, Guo-Xing

    2013-01-01

    Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP) mediated immune response, the role of reactive oxygen species (ROS) in brain-skin-axis regulation system remains unknown. The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress) which induced abnormal of hair cycle. Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in CRS mice skin. In addition, SP receptor antagonist (RP67580) reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation. Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss.

  17. Generation of inner ear sensory cells from bone marrow-derived human mesenchymal stem cells.

    PubMed

    Durán Alonso, M Beatriz; Feijoo-Redondo, Ana; Conde de Felipe, Magnolia; Carnicero, Estela; García, Ana Sánchez; García-Sancho, Javier; Rivolta, Marcelo N; Giráldez, Fernando; Schimmang, Thomas

    2012-11-01

    Hearing loss is the most common sensory disorder in humans, its main cause being the loss of cochlear hair cells. We studied the potential of human mesenchymal stem cells (hMSCs) to differentiate towards hair cells and auditory neurons. hMSCs were first differentiated to neural progenitors and subsequently to hair cell- or auditory neuron-like cells using in vitro culture methods. Differentiation of hMSCs to an intermediate neural progenitor stage was critical for obtaining inner ear sensory lineages. hMSCs generated hair cell-like cells only when neural progenitors derived from nonadherent hMSC cultures grown in serum-free medium were exposed to EGF and retinoic acid. Auditory neuron-like cells were obtained when treated with retinoic acid, and in the presence of defined growth factor combinations containing Sonic Hedgehog. The results show the potential of hMSCs to give rise to inner ear sensory cells.

  18. Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset

    PubMed Central

    Schreck, Mary; Petralia, Ronald S.; Wang, Ya-Xian; Zhang, Qiuxiang

    2017-01-01

    In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure, the synaptic ribbon, which organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity. However, additional variability in postsynapse size presents a challenge to determining the specific role of ribbon size in sensory encoding. To selectively assess the impact of ribbon size on synapse function, we examined hair cells in transgenic zebrafish that have enlarged ribbons, without postsynaptic alterations. Morphologically, we found that enlarged ribbons had more associated vesicles and reduced presynaptic calcium-channel clustering. Functionally, hair cells with enlarged ribbons had larger global and ribbon-localized calcium currents. Afferent neuron recordings revealed that hair cells with enlarged ribbons resulted in reduced spontaneous spike rates. Additionally, despite larger presynaptic calcium signals, we observed fewer evoked spikes with longer latencies from stimulus onset. Together, our work indicates that hair-cell ribbon size influences the spontaneous spiking and the precise encoding of stimulus onset in afferent neurons. SIGNIFICANCE STATEMENT Numerous studies support that hair-cell ribbon size corresponds with functional sensitivity differences in afferent neurons and, in the case of inner hair cells of the cochlea, vulnerability to damage from noise trauma. Yet it is unclear whether ribbon size directly influences sensory encoding. Our study reveals that ribbon enlargement results in increased ribbon-localized calcium signals, yet reduces afferent spontaneous activity and disrupts the timing of stimulus onset, a distinct aspect of auditory and vestibular encoding. These observations suggest that varying ribbon size alone can influence

  19. Hair cell regeneration or the expression of related factors that regulate the fate specification of supporting cells in the cochlear ducts of embryonic and posthatch chickens.

    PubMed

    Jiang, Lingling; Jin, Ran; Xu, Jincao; Ji, Yubin; Zhang, Meiguang; Zhang, Xuebo; Zhang, Xinwen; Han, Zhongming; Zeng, Shaoju

    2016-02-01

    Hair cells in posthatch chickens regenerate spontaneously through mitosis or the transdifferentiation of supporting cells in response to antibiotic injury. However, how embryonic chicken cochleae respond to antibiotic treatment remains unknown. This study is the first to indicate that unlike hair cells in posthatch chickens, the auditory epithelium was free from antibiotic injury (25-250 mg gentamicin/kg) in embryonic chickens, although FITC-conjugated gentamicin actually reached embryonic hair cells. Next, we examined and counted the cells and performed labeling for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) (triple or double labeling) in the injured cochlea ducts after gentamicin treatment at 2 h (h), 15 h, 24 h, 2 days (d), 3 d and 7 d after BrdU treatment in posthatch chickens. Our results indicated that following gentamicin administration, proliferating cells (BrdU+) were labeled for Atoh1/Math1 in the damaged areas 3d after gentamicin administration, whereas hair cells (PV+) renewed through mitosis (BrdU+) or direct transdifferentiation (BrdU-) were evident only after 5 d of gentamicin administration. In addition, Sox2 expression was up-regulated in triggered supporting cells at an early stage of regeneration, but stopped at the advent of mature hair cells. Our study also indicated that p27(kip1) was expressed in both hair cells and supporting cells but was down-regulated in a subgroup of the supporting cells that gave rise to hair cells. These data and the obtained dynamic changes of the cells labeled for BrdU, Sox2, Atoh1/Math1, PV or p27(kip1) are useful for understanding supporting cell behaviors and their fate specification during hair cell regeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Cytodifferentiation of hair cells during the development of a basal chordate.

    PubMed

    Gasparini, Fabio; Caicci, Federico; Rigon, Francesca; Zaniolo, Giovanna; Burighel, Paolo; Manni, Lucia

    2013-10-01

    Tunicates are unique animals for studying the origin and evolution of vertebrates because they are considered vertebrates' closest living relatives and share the vertebrate body plan and many specific features. Both possess neural placodes, transient thickenings of the cranial ectoderm that give rise to various types of sensory cells, including axonless secondary mechanoreceptors. In vertebrates, these are represented by the hair cells of the inner ear and the lateral line, which have an apical apparatus typically bearing cilia and stereovilli. In tunicates, they are found in the coronal organ, which is a mechanoreceptor located at the base of the oral siphon along the border of the velum and tentacles and is formed of cells bearing a row of cilia and short microvilli. The coronal organ represents the best candidate homolog for the vertebrate lateral line. To further understand the evolution of secondary sensory cells, we analysed the development and cytodifferentiation of coronal cells in the tunicate ascidian Ciona intestinalis for the first time. Here, coronal sensory cells can be identified as early as larval metamorphosis, before tentacles form, as cells with short cilia and microvilli. Sensory cells gradually differentiate, acquiring hair cell features with microvilli containing actin and myosin VIIa; in the meantime, the associated supporting cells develop. The coronal organ grows throughout the animal's lifespan, accompanying the growth of the tentacle crown. Anti-phospho Histone H3 immunostaining indicates that both hair cells and supporting cells can proliferate. This finding contributes to the understanding of the evolution of secondary sensory cells, suggesting that both ancestral cell types were able to proliferate and that this property was progressively restricted to supporting cells in vertebrates and definitively lost in mammals. Copyright © 2013 Elsevier B.V. All rights reserved.