| Project/Area Number |
17390156
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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 |
Applied pharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
YANAI Kazuhiko Tohoku University Graduate School ofMedicine, Professor, 大学院医学系研究科, 教授 (50192787)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA Ren Cyclotron and Radioisotope Center, Professor, サイクトロンRIセンター, 教授 (60143038)
TASHIRO Manabu Cyclotron and Radioisotope Center, Lecturer, サイクトロンRIセンター, 講師 (00333477)
KURAMASU Atsuo Tohoku University, Graduate School of Medicine, Lecturer, 大学院医学系研究科, 講師 (90302091)
OKAMURA Nobuyuki Tohoku University, Graduate School ofMedicine, Research Associate, 大学院医学系研究科, 助手 (40361076)
SAKURAI Eiko Tohoku University, Graduate School ofMedicine, Research Associate, 大学院医学系研究科, 助手 (90153949)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2006: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2005: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | Acetylcholinesterase / translational research / Alzheimer disease / Molecular imaging / Positron Emission Tomography (PET) / Histamine 1-11 receptors / Antihistamines / amyloid Aβ proteins |
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| Research Abstract |
1. Acetylcholinesterase was successfully measured in the human brain using [^<11>C]donepezil. The binding of [^<11>C]donepezil was significantly decreased in the brains of Alzheimer disease when compared to age-matched normal subjects. The binding of [^<11>C]donepezil was examined before and after the treatment of donepezil. The binding of [^<11>C]donepezil was markedly decreased after the treatment, suggesting that the therapeutic efficacy of donepezil can be measured using [^<11>C]donepezil.
2. Histamine HI. receptor occupancy was measured using [C]doxepin after the oral administration of antihistamines including olopatadine, bepotastine, diphenhydramine, and ketotifen. The H1 receptor occupancy was less than 20% of available H1 receptors in the brains of healthy normal volunteers after taking 10 mg bepotastine or 5 mg olopatadine, while those of 30 mg diphenhydramine and 1 mg ketotifen were more than 50 and 70 %, respectively. All these data suggest that the sedative properties of an
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tihistamines can be exactly measured using [^<11>C]doxepin-PET.
3. Using animal PET camera, we measured amyloid deposits in the periphery and brain of the mouse model. Amyloid deposits in the spleen can be detected in the mouse model of amyloidosis using [^<11>]BF-227, a carbon-11 derivative of benzoxazole. F-18 labeled PET ligands for imaging amyloid deposits in Alzheimer disease were developed using animal PET and the transgenic mouse model of amyloid deposits. The promising compounds were successfully screened using animal PET.
4. The study of the H1 receptor gene knockout mice demonstrates that the effects of histamine H1 receptor blockage are states-dependent. In socially-reared normal states, blocking H1 receptors impairs cognition. The H3 receptor blocking can stimulate the activity of histamine neurons, and can also improve cognition. However, in isolation-reared states, this is under stressful condition, the blockgae of H1 receptors attenuate the impaired cognition induced by social isolation. Less
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