| Project/Area Number |
12680762
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Toho University |
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Principal Investigator |
KOBAYASHI Masaaki Toho University School of Medicine, Department of Physiology, Assistant Professor, 医学部, 講師 (70246693)
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | hippocalcin / calcium-binding protein / knockout mice / hippocampusu / neuron / CREB / MAP kinase / memory / Hippocalcin / Calcium-binding protein / ERK / Hippocampus / Knockout mouse / Spatial memory / Activity-dependent gene expression |
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| Research Abstract |
Hippocalcin (HIP) is a member of the neuronal calcium sensors (NCS) family predominantly expressed in the hippocampal pyramidal cells. We have generated HIP deficient mice by homologous recombination. The morphological structure of HIP deficient hippocampus developed normally in light microscopic levels. Field EPSC, paired pulse facilitation and early-phase LTP were detected without any differences in HIP deficient hippocampus. However, learning abilities of the light-discrimination and Morris water maze were impaired in HIP deficient mice. In the present study, we used a semi-in vivo system composed of hippocampal slices, and Gluinduced gene expression cascades were assessed by using anti-phospho-Thr^<183>-Tyr^<185> ERK2 and anti-phospho-Ser^<133> CREB antibodies. NMDA treatment led a robust, progressive phosphorylation of ERK2 in wild type mice in time and concentration dependent manners. In HEP deficient mice, the NMDA-induced ERK2 phosphorylation was significantly lower than that in wild type mice. Effect of calcium ionophore mimiced the NMDA. On the contrary, treatments with protein kinase C- and cAMP dependent protein kinase- activators increased levels of phosphorylated ERK2 by similar levels both in wild type and HEP deficient mice. NMDA treatment also increased levels of phosphorylated CREB in wild type mice. ERK2 activation is known to be a key component for CREB phosphorylation which initiates c-fos mRNA synthesis. The levels of NMDA-induced CREB phosphorylation were significantly lower in HIP deficient mice.These results indicate that hippocalcin facilitates the activity-dependent gene expression, which plays an essential role in consolidation of long-term memory, by promoting the calcium-mediated ERK2 activation process.
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