PMID- 20599569
OWN - NLM
STAT- MEDLINE
DCOM- 20101221
LR  - 20211203
IS  - 1872-8111 (Electronic)
IS  - 0168-0102 (Linking)
VI  - 68
IP  - 2
DP  - 2010 Oct
TI  - Activation of mammalian target of rapamycin signaling in spatial learning.
PG  - 88-93
LID - 10.1016/j.neures.2010.06.008 [doi]
AB  - Novel protein synthesis is an essential element of various learning paradigms. 
      Although pharmacological and genetic strategies have indicated the importance of 
      translational activation in learning, the specific signaling pathways that are 
      activated in the brain remain unclear. Here, we show that mammalian target of 
      rapamycin (mTOR), a key serine/threonine protein kinase in translational control, 
      is activated in hippocampus of the learning rat as revealed by in vitro kinase 
      assay, Western blotting and immunohistochemistry. The substrates of mTOR, 
      eukaryotic initiation factor 4E-binding protein (4EBP) and p70S6 kinase (p70S6K) 
      are phosphorylated, and total protein synthesis is enhanced, in the learning 
      hippocampus. Furthermore, the inhibition of mTOR by chronic infusion of 
      rapamycin, a specific inhibitor of mTOR, into the ventricle retards the 
      establishment of spatial learning. Thus, mTOR signaling is activated during 
      learning, enhances translation, and plays a crucial role in the spatial learning.
CI  - 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights 
      reserved.
FAU - Qi, Sihua
AU  - Qi S
AD  - Department of Molecular Neurobiology, Brain Research Institute, Niigata 
      University, 1, Asahimachi, Niigata 951-8585, Japan.
FAU - Mizuno, Makoto
AU  - Mizuno M
FAU - Yonezawa, Kazuyoshi
AU  - Yonezawa K
FAU - Nawa, Hiroyuki
AU  - Nawa H
FAU - Takei, Nobuyuki
AU  - Takei N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100625
PL  - Ireland
TA  - Neurosci Res
JT  - Neuroscience research
JID - 8500749
RN  - 0 (Carrier Proteins)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Hippocampus/drug effects/*metabolism
MH  - Immunosuppressive Agents/pharmacology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Learning/drug effects/*physiology
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Phosphoproteins/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - Sirolimus/pharmacology
MH  - Space Perception/drug effects/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2010/07/06 06:00
MHDA- 2010/12/22 06:00
CRDT- 2010/07/06 06:00
PHST- 2010/04/13 00:00 [received]
PHST- 2010/06/14 00:00 [revised]
PHST- 2010/06/14 00:00 [accepted]
PHST- 2010/07/06 06:00 [entrez]
PHST- 2010/07/06 06:00 [pubmed]
PHST- 2010/12/22 06:00 [medline]
AID - S0168-0102(10)00165-3 [pii]
AID - 10.1016/j.neures.2010.06.008 [doi]
PST - ppublish
SO  - Neurosci Res. 2010 Oct;68(2):88-93. doi: 10.1016/j.neures.2010.06.008. Epub 2010 
      Jun 25.