| Project/Area Number |
16K07048
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SANGO Kazunori 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, プロジェクトリーダー (50291943)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 神経科学 / 脳神経疾患 / 糖尿病 / 細胞・組織 |
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| Outline of Final Research Achievements |
We established spontaneously immortalized Schwann cell lines from adult normal and aldose reductase (AR)-deficient C57BL/6 mice 1970C3 and IKARS1, and from normal adult Fischer344 rats IFRS1. These cell lines possess characteristic features of Schwann cells, such as immunoreactivity to glial cell markers and synthesis/secretion of neurotrophic factors.
The absent AR expression and inactivation of the polyol pathway in IKARS1 cells was confirmed by DNA microarray, real-time RT-PCR, western blotting and the measurement of intracellular polyol contents under high glucose (30 mM) conditions. These cell lines will be useful for the study of diabetic neuropathy.
IFRS1 possess fundamental ability to myelinate neurites in co-culture with adult rat dorsal root ganglion neurons, and will be useful for the study of demyelinating neuropathies; we observed that oxidative stress and impaired autophagy were involved in the demyelination-like changes induced by amiodarone, an anti-arrhythmic agent.
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| Academic Significance and Societal Importance of the Research Achievements |
我々が樹立した成熟動物由来シュワン細胞株は一定の増殖能を有し継代維持が容易であることに加え、成熟期シュワン細胞としての生物学的特性の多くを保持している。これら細胞株の特性を理解し活用すれば、諸種ニューロパチーの病態解明が進み有効な治療法の開発に繋がることが期待される。
本研究により、AR遺伝子欠損および対照マウス由来の細胞株IKARS1および1970C3が、糖尿病合併症の成因として重要なポリオール代謝経路を解析する上で、有用なツールとなることが示唆された。またラット由来細胞株IFRS1とDRGニューロンの共培養系は、アミオダロンをはじめとする脱髄性ニューロパチーの病態解明に有用と考えられた。
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