| Project/Area Number |
17390208
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | University of Toyama |
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Principal Investigator |
MATSUMOTO Kinzo University of Toyama, Institute of Natural Medicine, Professor (10114654)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Hideaki University of Toyama, Institute of Natural Medicine, Associate Professor (00345571)
TOHDA Michihisa University of Toyama, Institute of Natural Medicine, Associate Professor (20207525)
MURAKAME Yukihisa University of Toyama, Institute of Natural Medicine, Assistant Professor (00377269)
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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 |
¥16,170,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2005: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | chronic hypoperfusion / cognitive deficit / Kampo Medicine / chotosan / endogenous factor(s) / cholinergic system / gene expression / experimental ischemia / macrophage colony刺激因子 / gene analysis / saikokeishito / special cognitive deficit |
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| Research Abstract |
This research project aimed to search and identify factor(s) involved in the beneficial effects of Kampo medicines in an animal model of vascular dementia, and to elucidate such factors as a target molecule for development of new therapeutic drugs to treat vascular dementia. Chotosan (CTS) has been used for this aim since beneficial effects of CTS in patients with vascular dementia (VD) have been previously demonstrated by the placebo-controlled double blind study. The animals (mice, rats) received permanent occlusion of common carotid arteries (P2VO). CTS administration was started after P2VO. The effects of CTS were elucidated by using spatial and non-spatial cognitive performance and changes in gene expression in the brain as indices. P2VO animals exhibited impaired cognitive performance. CTS and a cholinesterase inhibitor tacrine but not saikokeishito, a Kampo formula with clinical applications which are completely different from those of CTS, significantly improved cognitive performance impaired by P2VO, suggesting that the beneficial effect of CTS on learning and memory is a characteristic pharmacological profile of CTS. We analyzed some marker genes related to the central cholinergic system, since this system plays an important role in learning and memory. Our results revealed that expression systems of genes encoding markers of the cholinergic system, particularly choline acetyltransferase and muscarinic receptors, are involved in the effect of CTS. Moreover, we have found from DNA array analysis that macrophage colony stimulating factor mRNA is one of genes, the expression of which is susceptible to P2VO and that CTS elevates the expression of this gene in the brain via a protein kinase C mechanism. Since this factor attenuates ischemia- and trauma-induced neuronal damage and exhibits trophic effects on cholinergic neurons, our findings suggest that M-CSF system may be one of mechanisms involved in beneficial action of CTS in patents with VD.
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