Project/Area Number |
17390209
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General internal medicine (including Psychosomatic medicine)
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Research Institution | University of Toyama |
Principal Investigator |
TOHDA Michihisa University of Toyama, Inst. of Natl. Med, Associate Professor (20207525)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Kinzo University of Toyama, Inst. of Natl. Med, Professor (10114654)
KOMATSU Katsuko University of Toyama, Inst. of Natl. Med, Professor (50225570)
TANAKA Ken University of Toyama, Inst. of Natl. Med, Associate Professor (60418689)
TOHDA Chihiro University of Toyama, Inst. of Natl. Med, Assistant Professor (10272931)
OBI Ryousuke University of Toyama, Grad. School of Med. & Pharm. Sci, Assistant Professor (60401816)
後藤 博三 富山大学, 和漢医薬学総合研究所, 助教授 (40313598)
村上 孝寿 富山大学, 和漢医薬学総合研究所, 助手 (00377269)
|
Project Period (FY) |
2005 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥15,830,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥630,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥10,400,000 (Direct Cost: ¥10,400,000)
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Keywords | Wakan-yaku / Chotosan / dementia / depressive disorder / M-CSF / BNIP-3 / Hochuekkito / mRNA expression / 和漢処方 / 記憶学習 / 両方向性調節 / 遺伝子発現変化 / C6グリオーマ / セロトニン / 抗うつ / ウイリアムズ症候群 / CSF / NG108-15 |
Research Abstract |
Wakan-yaku, Sino-Japanese traditional medicine, is systematized medical care that has been practiced for several hundred years or more in China and Japan. It would be useful to apply this systematized concept of Wakan-yaku to search for intrinsic molecules and clarify the functions involved in depressive and/or other psychological disorders. The results are as follows: 1) BNIP-3 is a candidate for an intrinsic factor related to antidepressive effects. This hypothesis was derived firm a DNA array assay followed by detailed analysis of the array results in Hochuekkito-, a kind of Wakan-yaku, treated NG108-15 cells. This mRNA expression enhancement of BNIP-3 was also observed on treatment with various antidepressants in a concentration-dependent manner. 2) I paid attention to the dementia-curative effect of "Chotosan", and tried to search for an endogenous factor related to dementia using Wakan-yaku. As a result, expression enhancement of some genes such as IDE, neprilysin, and 〓7 nicotin
… More
ic receptors was observed. Among these, since little information is available concerning the relationship between M-CSF expression and dementia, examinations to clarify the physiological significance and molecular mechanisms of the regulation of M-CSF mRNA expression were conducted. The following results were obtained: a) M-CSF mRNA expression was also enhanced in the ischemic condition alone in the rat brain. B) Chotosan reinforced the action in the early period and at low a concentration. C) The PKC system was involved in this reinforcement effect. D) On the other hand, Chotosan switched to expression inhibition at a higher concentration, and the elevation of cAMP was related to this effect. E) I also obtained results suggesting that M-CSF was involved in glial function depending on the cell condition, proliferation period or resting stage. These results suggest that Chotosan effectively assists in the elevation of M-CSF mRNA expression, which has been reportedly shown protective effects on the nervous system, and that it might prevent side effect onset afterwards by switching to inhibition. For example, nitric oxide is well-know to exhibit both beneficial and toxic effects, vasodilatation and cell death. Studies for the "isolation of the effective action" by Wakan-yaku will be interesting as a future research field. In addition to the above results, through these research funds, I also studied whether: 3) Tokishakuyakusan shows a female hormone-like effect through mRNA expression changes such as the enhancement of PCAP and a decrease in progesterone receptors, and about 4) 5-HT2C receptor mRNA editing and its physiologic significance. Less
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