Inhibiting neuronal alpha-synuclein accumulation caused by oli godendrocytic inclusions
| Project/Area Number |
22500326
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | National Center for Geriatrics and Gerontology |
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Principal Investigator |
YAZAWA Ikuru 独立行政法人国立長寿医療研究センター, バイオリソース研究室, 室長 (20312217)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 脳神経疾患 / 病理学 / 神経科学 / オリゴデンドロサイト / 神経変性 / 神経変性疾患 / synuclein / 多系統萎縮症 / モデルマウス / グリア細胞質内封入体 / α-synuclein / 多系統委縮症 / グリア細胞封入体 / 初代培養 / 神経変性治療 |
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| Research Abstract |
Multiple system atrophy is a neurodegenerative disease caused by α-synuclein accumulation in oligodendrocytes and neurons. We generated a transgenic mouse model in which human α-synuclein was overexpressed in oligodendrocytes. Our previous studies have revealed that oligodendrocytic α-synuclein inclusions induced neuronal α-synuclein accumulation, resulting in progressive neuronal degeneration in mice. We also demonstrated that an insoluble complex of a-synuclein and ss-III tubulin in microtubules progressively accumulated in neurons. α-Synuclein accumulation is increased in the presynaptic terminals of transgenic mice neurons and may reduce neurotransmitter release. In the present study, we investigated the effects of neuronal α-synuclein accumulation on synaptic function in transgenic mice. Using whole-cell patch-clamp recording, we demonstrated synaptic dysfunction in transgenic mice, and a microtubule depolymerizing agent restored the normal function in transgenic mice.
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Report
(4 results)
Research Products
(33 results)
