| Project/Area Number |
15300122
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Niigata University |
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Principal Investigator |
TAKEI Nobuyuki Niigata University, Brain Research Institute, Associate Professor, 脳研究所, 助教授 (70221372)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | neuron / translational control / BDNF / mTOR / local protein synthesis / neural plasticity / LTP / spatial learning / 翻訳伸展 / eEF2 / eEF2キナーゼ / 4EBP / p70S6K / 蛋白合成 / 神経活動 / eIF2a / カイニン酸 / グルタミン酸 |
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| Research Abstract |
Activity-dependent local translation at the perisynaptic area is implicated in synapse-wide alterations of function and morphology. The molecular mechanisms of local translation activation, however, have yet to be illuminated. We have shown that local protein synthesis and translational activation in neuronal dendrites were up-regulated by brain-derived neurotrophic factor (BDNF) in a rapamycin-sensitive manner. In parallel, BDNF activates of mammalian target of rapamycin (mTOR) signaling pathways in dendrites. BDNF also enhances elongation process through the mTOR pathway. Inhibition of mTOR activity by rapamycin and knockdown of mTOR by siRNA completely suppresses the action of BDNF.
The present results indicate that mTOR-dependent translation activation at multiple processes is essential for the up-regulation of local protein synthesis in neuronal dendrites. We further showed the evidences that mTOR-dependent translational activation occurred during plastic event, such as LTP and spatial memory paradigms in the CNS. As rapamycin canceled these effects, mTOR-dependent translational activation is essential for the certain types of neural plasticity.
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