期刊
NEUROSCIENCE RESEARCH
卷 68, 期 2, 页码 88-93出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neures.2010.06.008
关键词
mTOR; p70S6K; 4EBP; Translation; Protein synthesis; Rapamycin
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science
- Japan Science and Technology Corporation (Core Research for Evolutional Science and Technology: CREST)
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. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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