2003 Fiscal Year Final Research Report Summary
Influence of membrane lipid metabolism on cerebral amyloid deposition and neurodegeneration.
| Project/Area Number |
13480250
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Gunma University |
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Principal Investigator |
YAMAGUCHI Haruyasu Gunma University, School of Health Sciences, Professor, 医学部, 教授 (00158114)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Atsushi Gunma University, School of Medicine, Assistant Professor, 医学部, 講師 (80225862)
YANAGISAWA Katsuhiko National Institute for Longevity Science, Director, 痴呆疾患研究部, 部長 (10230260)
C.FUJITA Shinobu Mitsubishi Kasei Life Science Institute, Senior Researcher, 生命科学研究所, 主任研究員
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| Project Period (FY) |
2001 – 2003
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| Keywords | Alzheimer's disease / amyloid / dementia / ApoE / animal model / raft |
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| Research Abstract |
We examined the ultrastructure of rafts in rat brain tissue by pre-embedding immunoelectron microscopy using flotillin-1 antibody, which is biochemical marker of lipid rafts, and BCθ, which is nicked and biotinylated θ-toxin, and binds to membrane cholesterol of rafts. Flotillin-1-and BCθ-labeled areas were patchy and prominent on the plasma membranes of small processes and synapses in the neuropil. The size of flotillin-1 labeling was 40 to 200nm.In addition, the membrane of lysosome and Golgi apparatus were frequently labeled for flotillin-1 with a patchy pattern. Flotillin-1 and BCθ were mostly colocalized in double immunolabeling on a part of the plasma membranes of small processes and secondary lysosome membranes. We first indicate that flotillin-1 localizes to BCθ-positive cholesterol-rich membrane microdomains in vivo, and that flotillin-1 and BCθ could be an ultrastructural rafts marker in neural tissue. We also examined the relation between lipid raft and cerebral β-amyloid deposition in the Tg2576 transgenic mouse.
Moreover, we found a striking difference in the distribution of membrane cholesterol. ApoE4 knock-in mice showed an approximately 2-fold increase in exofacial leaflet cholesterol compared with apoE3 knock-in mice and wild-type mice.
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