| Project/Area Number |
03454242
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
NAKAMURA Shigenobu Hiroshima Univ.School of Medicine, Prof., 医学部, 教授 (30026843)
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| Co-Investigator(Kenkyū-buntansha) |
MIMORI Yasuyo Hiroshima Univ.School of Medicine, Research Associates., 医学部, 助手 (50166112)
KOHRIYAMA Tatsuo Hiroshima Univ.School of Medicine, Research Associates., 医学部, 助手 (80195693)
ISHIZAKI Fumiko Hiroshima Univ.Medical Hospital, Assistant Prof., 医学部・附属病院, 講師 (60093572)
KATAYAMA Sadao Hiroshima Univ.Medical Hospital, Research Associates., 医学部・附属病院, 助手 (00211160)
YAMAMURA Yasuhiro Hiroshima Univ.School of Medicine, Associate Prof., 医学部, 助教授 (10106388)
安部 明夫 広島大学, 医学部・付属病院, 助手 (10159436)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Alzheimer's disease / Amyloid protein / Acetylcholine / C-jun / C-fos / Senile plaque / Acetylcholinesterase / Glutamate / 輸送蛋白 / 第5染色体 / β-アミロイド蛋白前駆体 / アセチルコリンエステラーゼ / βーアミロイド蛋白前駆体 / cーfos / cーjun / アセチルコリンエステラ-ゼ |
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| Research Abstract |
It has been possible to measure the expression of mRNA of beta-amyloid protein, c-fos, c-jun and so on. We measured the expression of beta-amyloid protein mRNA or other other mRNA by this method using autopsied brains. We determined the determined the ratio of (APP751mRNA+APP770)with protease inhibitor/APP695mRNA without protease inhibitor in the beta-amyloid protein precursor, using autopsied brains. THe ratio of (APP751mRNA+APP770mRNA)/APP695mRNA increased according to the advance in age either in Alzheimer's disease or control brain. On the other hand, the content of acetylcholine in the brain decreased in the brain according to the age. Acetylcholine increased the expression of c-fos or c-jun mRNA after 30 min through m3 receptor in SK-N-SH cells. Consequently, the expression of beta-amyloid protein precursor increased after 8 hours. In the experiment, the addtion of protein kinase C inhibitor suppressed the expression of APP.We also measured the change in expression of APPmRNA by thrombin addition. The addition of thrombin increased the expression of APPmRNA time dependently up to 24 hours. However, plasmin, tissue plasminogen activator or phorbol myristic acid did not show the increase in APPmRNA.The degradative enzyme of acetylcholine, acetylcholinesterase (AChE) was observed in senile plaque or Alzheimer neurofibrillary tangle. We examined properties of AChE in the preparation rich in senile plaque prepared from autopsied Alzheimer brains. We revealed that AChE in senile plaque rich fraction showed 12S or 16S by sucrose density centrifugation and was converted to 10S by collagenase treatment, suggesting that AChE in senile plaque would be type A contaning collagen tail. We cloned glutame transpoter from human brain and elucidated its properties.
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