2003 Fiscal Year Final Research Report Summary
Molecular pharmacological studies in the animal model for Alzheimer's disease
| Project/Area Number |
13672407
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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 |
応用薬理学・医療系薬学
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| Research Institution | Fukuoka University |
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Principal Investigator |
IWASAKI Katsunori Fukuoka Univ., Fac.of Pharmaceutical Sciences, Associate Prof., 薬学部, 助教授 (10183196)
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| Co-Investigator(Kenkyū-buntansha) |
MISHIMA Kenichi Fukuoka Univ., Fac.of Pharmaceutical Sciences, Assistant Prof., 薬学部, 助手 (00320309)
FUJIWARA Michihiro Fukuoka Univ., Fac.of Pharmaceutical Sciences, Professor, 薬学部, 教授 (10091331)
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| Project Period (FY) |
2001 – 2003
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| Keywords | ALZHEIMER'S DISEASE / CEREBRAL ISCHEMIA / ChE-inhibitor / RAT / MAZE PERFORMANCE / MEMORY |
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| Research Abstract |
β-Amyloid (Aβ) deposited in the senile plaques is thought to be a main cause of Alzheime's disease(AD). According to this AR hypothesis, we tried to develop new animal models of AD. (1) We found that human Tau transgenic mice (R406W) showed behavioral depression at the age of 10 months and SSRI inhibited this behavior. These facts suggested that serotonergic mechanism may play an important role at the early stage of AD. (2) Non-transgenic animal models of AD are also necessary for new drug development. Firstly, we developed a combination treatment of brief cerebral ischemia with intracerebral injection of Aβ1-42 in rats using 8-arm radial maze task. Neither Aβ1-42-treated nor ischemia-subjected rats showed the memory disturbances at the retention test of 7th day. On the other hand, the combination treatment of Aβ1-42 with 10 mm ischemia showed significant disruption of spatial memory Secondary, we combined the ovariectomy (OVX) and intracerebral injection of Aβ1-42 in female rats because of the fact that AD occurs with greater incidence in postmenopausal women. The combination treatment of Aβ1-42 with OVX also slowed significant decrease of serum estrogen and showed memory disturbance in 8-arm radial maze task. Further investigation of these two models indicated that Aβ-induced hippocampal apoptosis and ACh dysfunction may cause the AD's dementia and drugs inhibited these symptoms may be useful for the treatment of AD.
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Research Products
(22 results)
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[Publications] Yoshitaka Tatebayashi, Tomohiro Miyasaka, De-Hua Chui, Takumi Akagi, Kenichi Mishima, Katsunori Iwasaki, Michihiro Fujiwara, Kentaro Tanemura, Miyuki Murayama, Koichi Ishiguro, Emmanuel Planei, Shinji Sato, Tsutomu Hashikawa, amd Akihiko Takashima: "Tau filament formation and associative memory deficit in aged mice expressing mutant (R406W) human tan"Proc.Natl.Acad.Sci.. vol.99(No.21). 13896-13901 (2002)
Description
「研究成果報告書概要(欧文)」より
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