The effect of steroid hormones on synaptogenesis and its mechanisms
| Project/Area Number |
17500241
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Toyo University (2006-2007)
St. Marianna University School of Medicine (2005) |
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Principal Investigator |
OHTNAI Ritsuko Toyo University, Department of Life Sciences, Professor (00161183)
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| Co-Investigator(Kenkyū-buntansha) |
MIYASHITA Tomoyuki Tokyo Metropolitan Institute of Neuroscience, Department of Life Sciences, Research Fellow (70270668)
WATANABE Chiho The University of Tokyo, Department of Human Ecology, Professor (70220902)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | synapse / synapsin I / development / estrogen / estrogen receptor / 細胞・組織 / 神経科学 / プロテオーム / シグナル伝達 / 大脳皮質 / シナプス形成 / プロテオミクス解析 / 培養細胞 / エストロゲン / APC蛋白質 / CaMキナーゼ |
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| Research Abstract |
It has become increasingly clear that estrogens, one of steroids hormones, play an important role in learning and memory across the lifespan. Estrogens also play critical roles in the sexual differentiation of the developing rat hypothalamus to form gender-specific neural circuit during about one perinatal week, critically sensitive period to estrogen. The purpose of this research was to investigate the effect of estrogens on neurons, especially on synaptogenesis during development. We performed this research by using cultured hypothalamic and cortical cells and observed estradiol-17 beta (E2)-mediated changes in synaptogenesis. In some studies, we also used endocrine disruptors with estrogenic activities including bisphenol-A, nonylphenol and cadmium (Cd). Treatment of E2 as well as membrane impermeable E2 conjugated to BSA (E2-BSA) for a week significantly increased the punctual area of synapsin I. The increase in punctuate area of synapsin I induced by E2 or E2-BSA was not inhibited by estrogen receptor antagonist, ICI 182,780. Subcellular distribution pattern of synapsin I, diffusely dispersing or punctually clustering, is controlled by multiple protein kinases. Immunoblots showed that E2 suppressed phosphorylation of synapsin I at sites 1, 2 and 3. These sites are known to be phosphorylated mainly by cAMP-dependent protein kinase (PKA) and Ca2+-calmodulin-dependent protein kinase (CaMK) I and II. On the other hand, E2 did not affect phosphorylation at sites 4/5 and 6 which are phosphorylated mainly by mitogen activated protein kinase (MAPK) . These studies and other inhibitor studies suggested that E2-mediated changes of synapsin I am caused through the non- genomic signaling.
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Report
(4 results)
Research Products
(50 results)
