PMID- 25918725
OWN - NLM
STAT- MEDLINE
DCOM- 20160125
LR  - 20211203
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2015
DP  - 2015
TI  - Inhibition of mTOR by Rapamycin Results in Auditory Hair Cell Damage and 
      Decreased Spiral Ganglion Neuron Outgrowth and Neurite Formation In Vitro.
PG  - 925890
LID - 10.1155/2015/925890 [doi]
LID - 925890
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.
FAU - Leitmeyer, Katharina
AU  - Leitmeyer K
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
FAU - Glutz, Andrea
AU  - Glutz A
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
FAU - Radojevic, Vesna
AU  - Radojevic V
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
FAU - Setz, Cristian
AU  - Setz C
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
FAU - Huerzeler, Nathan
AU  - Huerzeler N
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
FAU - Bumann, Helen
AU  - Bumann H
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
FAU - Bodmer, Daniel
AU  - Bodmer D
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
FAU - Brand, Yves
AU  - Brand Y
AD  - Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 
      Basel, Switzerland ; Clinic for Otolaryngology, Head and Neck Surgery, University 
      Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150331
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Multiprotein Complexes)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Hair Cells, Auditory/*enzymology/pathology
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/metabolism
MH  - Neurites/*enzymology/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Sirolimus/*adverse effects/pharmacology
MH  - Spiral Ganglion/*enzymology/pathology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
PMC - PMC4395993
EDAT- 2015/04/29 06:00
MHDA- 2016/01/26 06:00
PMCR- 2015/03/31
CRDT- 2015/04/29 06:00
PHST- 2014/12/22 00:00 [received]
PHST- 2015/03/10 00:00 [revised]
PHST- 2015/03/11 00:00 [accepted]
PHST- 2015/04/29 06:00 [entrez]
PHST- 2015/04/29 06:00 [pubmed]
PHST- 2016/01/26 06:00 [medline]
PHST- 2015/03/31 00:00 [pmc-release]
AID - 10.1155/2015/925890 [doi]
PST - ppublish
SO  - Biomed Res Int. 2015;2015:925890. doi: 10.1155/2015/925890. Epub 2015 Mar 31.