Studies on regulatory mechanisms of brain function by protein kinase C-mediated SNAP-25 phosphorylation.
Project/Area Number |
24240055
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | Kitasato University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
MIYAOKA Hitoshi 北里大学, 医学部, 教授 (40209862)
ITAKURA Makoto 北里大学, 医学部, 准教授 (30398581)
OKADA Daisuke 北里大学, 医学部, 講師 (10211806)
YAMAMORI Saori 北里大学, 医学部, 講師 (30464803)
AZUMA Sadahiro 北里大学, 医学部, 助教 (80348507)
KATAOKA Masakazu 信州大学, 工学部, 准教授 (90332676)
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Research Collaborator |
WATANABE Shigeru
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥39,260,000 (Direct Cost: ¥30,200,000、Indirect Cost: ¥9,060,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2012: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
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Keywords | タンパク質リン酸化 / プロテインキナーゼC / SNAREタンパク質 / 開口放出 / てんかん / 不安用行動 / 脳波測定 / SNAP-25 / 遺伝子改変マウス / 不安様行動 / ピロカルピンモデル / BDNF / ノックインマウス / 行動異常 / 抗てんかん薬 / ドーパミン / ストレス |
Outline of Final Research Achievements |
Regulatory mechanisms and functional roles of SNAP-25 phosphorylation were studied using a knock-in mouse with a single amino acid substitution at a PKC-dependent phosphorylation site. We found that the dephosphorylation of SNAP-25 was mediated by PP2A through Ca2+-dependent and Ca2+-independent mechanisms, and SNAP-25 phosphorylation played a role in stress response of animals. The SNAP-25 mutant mouse exhibited several distinct phenotypes, including anxiety-like behavior and epileptogenesis. We found that anxiety-like behaviors appeared through several different mechanisms and dopamine D2 receptor was involved in some mechanisms. We conducted long-term continuous video electroencephalogram recordings of the mice and revealed the process of epileptogenesis and epileptic maturation in detail. We developed a unique drug administration system to free-moving mouse during continuous electroencephalogram recording, which would be useful for the discovery of new antiepileptic drugs.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] BDNF pro-peptide actions facilitate hippocampal LTD and are altered by the common BDNF polymorphism Val66Met.2015
Author(s)
Mizui T, Ishikawa Y, Kumanogoh H, Lume M, Matsumoto T, Hara T, Yamawaki S, Takahashi M, Shiosaka S, Itami C, Uegaki K, Saarma M, Kojima M.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 112
Issue: 23
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Synaptosomal-associated protein 25 mutation induces immaturity of the dentate granule cells of adult mice.2013
Author(s)
Ohira K, Kobayashi K, Toyama K, Nakamura HK, Shoji H, Takao K, Takeuchi R, Yamaguchi S, Kataoka M, Otsuka S, Takahashi M, Miyakawa T.
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Journal Title
Molecular Brain
Volume: 6
Issue: 1
Pages: 12-12
DOI
Related Report
Peer Reviewed
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[Journal Article] Accumulation of a-synuclein triggered by presynaptic dysfunction2012
Author(s)
Nakata Y, Yasuda T, Fukaya M, Yamamori S, Itakura M, Nihira T, Hayakawa H, Kawanami A, Kataoka M, Nagai M, Sakagami H, Takahashi M, Mizuno Y, Mochizuki H
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Journal Title
J. Neurosci
Volume: 32
Issue: 48
Pages: 17186-17196
DOI
Related Report
Peer Reviewed
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