Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro.

Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However,...

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Publicado en:BioMed Research International Vol. 2015; pp. 1 - 11
Autores principales: Leitmeyer, Katharina, Glutz, Andrea, Radojevic, Vesna, Setz, Cristian, Huerzeler, Nathan, Bumann, Helen, Bodmer, Daniel, Brand, Yves
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell 3/31/2015
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 3/31/2015
      vid: 2015
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2015/925890
        109273863
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        atl: Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro.
      aug:
        au:
          Leitmeyer, Katharina
          Glutz, Andrea
          Radojevic, Vesna
          Setz, Cristian
          Huerzeler, Nathan
          Bumann, Helen
          Bodmer, Daniel
          Brand, Yves
        affil: Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland
      sug:
        subj:
          Sirolimus
          Hair Cells
          Ganglionic Blockers
          Spiral Ganglion
          In Vitro Studies
          Descriptive Statistics
          Data Analysis Software
          Odds Ratio
          Confidence Intervals
          Switzerland
          Blotting, Western
          Tissue Culture Techniques
          Immunohistochemistry
          Histology
          Funding Source
      ab: Rapamycin is an antifungal agent with immunosuppressive properties. Rapamycin inhibits the mammalian target of rapamycin (mTOR) by blocking the mTOR complex 1 (mTORC1). mTOR is an atypical serine/threonine protein kinase, which controls cell growth, cell proliferation, and cell metabolism. However, less is known about the mTOR pathway in the inner ear. First, we evaluated whether or not the two mTOR complexes (mTORC1 and mTORC2, resp.) are present in the mammalian cochlea. Next, tissue explants of 5-day-old rats were treated with increasing concentrations of rapamycin to explore the effects of rapamycin on auditory hair cells and spiral ganglion neurons. Auditory hair cell survival, spiral ganglion neuron number, length of neurites, and neuronal survival were analyzed in vitro. Our data indicates that both mTOR complexes are expressed in the mammalian cochlea. We observed that inhibition of mTOR by rapamycin results in a dose dependent damage of auditory hair cells. Moreover, spiral ganglion neurite number and length of neurites were significantly decreased in all concentrations used compared to control in a dose dependent manner. Our data indicate that the mTOR may play a role in the survival of hair cells and modulates spiral ganglion neuronal outgrowth and neurite formation.
      pubtype: Academic Journal
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        tables/charts
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      ougenre: Article
    language: English
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