| Project/Area Number |
17500249
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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 | University of Toyama |
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Principal Investigator |
TOHDA Chihiro University of Toyama, Institute of Natural Medicine Research Center for Ethnomedicine Division of Biofunctional Evaluation, Assistant Professor (10272931)
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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 |
¥3,850,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Withanoside IV / Sominone / Memory improvement / Dendrite / RET / ACK1 / Neuronal network / Spinal cord injury / withanolide類 / シナプス形成 / 末梢性ミエリン / axon / neuregulin-I / estrogen receptor / PI3 kinase / 抗痴呆 / 中枢神経損傷 / neuron / myelin |
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| Research Abstract |
Oral administration of withanoside IV (10 μmol/kg/day), an isolated compound from roots of Withania somnifera significantly improved memory deficits in Aβ(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. The treatment with withanoside IV could enhance the object recognition memory in normal mice. In spinal cord injured mice, per oral treatment with withanoside IV (10 μmol/kg/day, for 21 days) improved locomotor functions in mice, and increased axonal density and the peripheral nervous system myelin level.
Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 μM) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 μM Aβ(25-35).
To clarify the molecular mechanism of sominone, we identified receptors or associated molecules in primary cultured neurons, which were phosphorylated by sominone stimulation using phosphorylation antibody arrays. The level of phosphorylated RET increased in microglias and neurons. The level of phosphorylated ACK1 increased in neurons. Knockdown experiments using siRNA showed that both RET and ACK1 were involved in dedritic extension. These results suggest that roles of RET and ACK1 as key molecules for reconstruction of the neuronal
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