PMID- 22273489
OWN - NLM
STAT- MEDLINE
DCOM- 20130124
LR  - 20211203
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 46
IP  - 2
DP  - 2012 May
TI  - Role of mTOR in neuroprotection and axon regeneration after inflammatory 
      stimulation.
PG  - 314-24
LID - 10.1016/j.nbd.2012.01.004 [doi]
AB  - Mature retinal ganglion cells (RGCs) do not normally regenerate injured axons, 
      but degenerate after axotomy. However, inflammatory stimulation (IS) enables RGCs 
      to survive axotomy and regenerate axons in the injured optic nerve. Similar 
      effects are achieved by the genetic deletion of phosphatase and tensin homolog 
      (PTEN) and subsequent mammalian target of rapamycin (mTOR) activation. Here, we 
      report that IS prevents the axotomy-induced decrease of mTOR activity in RGCs in 
      a CNTF/LIF-dependent manner. Inactivation of mTOR significantly reduced the 
      number of long axons regenerating in the optic nerve, but surprisingly, did not 
      affect the initial switch of RGCs into the regenerative state, or the 
      neuroprotective effects associated with IS. In vitro, inhibition of mTOR activity 
      reduced regeneration on myelin or chondroitin sulfate proteoglycans (CSPGs), but 
      not on a growth-permissive substrate. Thus, mTOR activity is not generally 
      required for neuroprotection or switching mature neurons into an active 
      regenerative state, but it is important for the maintenance of the axonal growth 
      state and overcoming of inhibitory effects caused by myelin and CSPGs.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Leibinger, Marco
AU  - Leibinger M
AD  - Department of Neurology, Heinrich Heine University of Dusseldorf, Dusseldorf, 
      Germany
FAU - Andreadaki, Anastasia
AU  - Andreadaki A
FAU - Fischer, Dietmar
AU  - Fischer D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120120
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (Inflammation Mediators)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Axons/*physiology
MH  - Cells, Cultured
MH  - Inflammation Mediators/metabolism/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myelin Sheath/physiology
MH  - Nerve Regeneration/*physiology
MH  - Neural Inhibition/physiology
MH  - *Neuroprotective Agents
MH  - Optic Nerve Injuries/pathology/physiopathology/*prevention & control
MH  - Retinal Ganglion Cells/physiology
MH  - TOR Serine-Threonine Kinases/metabolism/*physiology
EDAT- 2012/01/26 06:00
MHDA- 2013/01/25 06:00
CRDT- 2012/01/26 06:00
PHST- 2011/11/30 00:00 [received]
PHST- 2012/01/03 00:00 [revised]
PHST- 2012/01/09 00:00 [accepted]
PHST- 2012/01/26 06:00 [entrez]
PHST- 2012/01/26 06:00 [pubmed]
PHST- 2013/01/25 06:00 [medline]
AID - S0969-9961(12)00019-8 [pii]
AID - 10.1016/j.nbd.2012.01.004 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2012 May;46(2):314-24. doi: 10.1016/j.nbd.2012.01.004. Epub 2012 
      Jan 20.