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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Bibliographic Details
Published in:BioMed research international 2015-01, Vol.2015 (2015), p.1-10
Main Authors: Brand, Yves, Bumann, Helen, Huerzeler, Nathan, Setz, Cristian, Radojevic, Vesna, Glutz, Andrea, Leitmeyer, Katharina, Bodmer, Daniel
Format: Article
Language:English
Subjects:
Animals
Cancer
Cell cycle
Cell division
Cell growth
Cell Survival - drug effects
Complications and side effects
Experiments
Hair cells (Mechanoreceptors)
Hair Cells, Auditory - enzymology
Hair Cells, Auditory - pathology
Health aspects
Hearing loss
Kinases
Mechanistic Target of Rapamycin Complex 1
Metabolism
Multiprotein Complexes - metabolism
Neurites - enzymology
Neurites - pathology
Neurons
Proteins
Rapamycin
Rats
Rats, Wistar
Sirolimus - adverse effects
Sirolimus - pharmacology
Spiral Ganglion - enzymology
Spiral Ganglion - pathology
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - metabolism
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Summary: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.
ISSN:2314-6133
2314-6141
DOI:10.1155/2015/925890