| Project/Area Number |
12670085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Nagoya University |
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Principal Investigator |
YAMADA Kiyofumi University Hospital Associate Professor, 医学部・附属病院, 助教授 (30303639)
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| Co-Investigator(Kenkyū-buntansha) |
NAWA Hiroyuki Niigata University, Brain Research Institute, Professor, 脳研究所, 教授 (50183083)
NABESHIMA Toshitaka University Hospital Nagoya University Professor, 医学部・附属病院, 教授 (70076751)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | BDNF / Learning and memory / Synaptic plasticity / NMDA receptors / Fyn / c-Fos / B-Amy|oid / Hippocampus / 空間記憶 / 一酸化窒素 / β-アミロイド蛋白 / アンチセンス / 放射状迷路学習 |
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| Research Abstract |
We investigated cellular mechanisms by which brain-derived neurotrophic factor (BDNF) facilitates learning and memory. Our findings indicated that (1) Spatial memory formation in an 8-arm radial arm maze is associated with an increase in the mRNA levels of BDNF and its receptor TrkB phosphorylation in the hippocampus. (2) Continuous intracerebroventricular infusion of antisense BDNF oligonucleotide inhibited the processes of spatial memory acquisition as well as memory retention and/or retrival. (3) Activation of PI3-K/Akt signaling pathway and new protein synthesis is associated with BDNF-dependent learning and memory. (4) Interaction between BDNF/TrkB signaling and NMDA receptors via a src-family tyrosine kinase Fyn is also important for spatial memory formation.
These results suggest that BDNF plays a crucial role in spatial memory formation and maintenance by activating new protein synthesis and NMDA receptors in the hippocampus, via TrkB/PI3-K/Akt and TrkB/Fyn/NR2B signaling pathways, respectively.
Furthermore, we obtained some data regarding neural mechanism of spatial memory : (1)The CA3 region of the hippocampus is obligatory for spatial memory formation in the radial arm maze. (2) The activation of PKA/CREB signaling pathway in the hippocampus plays an important role in spatial memory formation in the radial arm maze. (3) A novel learning and memory task using an 8-arm radial arm maze was developed and characterized. (4) Direct infusion of p-amyloid or okadaic acid into the brain induces learning and memory impairment.
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