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

• 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
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2015/925890

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.