| Project/Area Number |
16500212
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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 | Asahikawa Medical College |
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Principal Investigator |
YOSHIDA Shigetaka Asahikawa Medical College, Medical School, Professor, 医学部, 教授 (20230740)
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| Co-Investigator(Kenkyū-buntansha) |
BANDO Yoshida Asahikawa Medical College, Medical School, Assistant Professor, 医学部, 助手 (20344575)
TERAYAMA Ryuji Okayama University, Dental School, Assistant Professor, 歯学部, 助手 (60333689)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Neuropsin / Oligodendrocytes / Protease / Protease M / Spinal cord injury / Multiple sclerosis / セリンプロテアーゼ / 脱髄 |
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| Research Abstract |
In this research project, we have investigated on the function of 2 serine proteases, neuropsin and protease M to demyelination. We obtained following results :
1.We performed double labeling experiments and found that neuropsin and protease M were expressed by mature oligodendrocytes.
2.We induced experimental allergic encephalopathy (EAE), an animal model of multiple sclerosis in mice. In this model, neuropsin and protease M expressed stronger in oligodendrocytes. In shiverer mice, which defect myelin basic protein (MBP) gene, protease M expression was markedly suppressed. Cuprizone diet, which selectively degenerates oligodendrocytes, decreased protease M expression and remyelination induced by normal diet without cuprizone increased the expression of protease M.
3.The number of survived oligodendrocytes after spinal cord injury was significantly more in neuropsin-knockout (KO) mice than in the wild type. The resultant motion activity of the hind limb was significantly better in neuropsin-KO mice. Neuropsin-KO mice also scored better in behavioral tests.
4.When protease M was overexpressed in primary oligodendrocytes, no prominent change was observed. However, suppression of protease M expression with RNAi decreased the expression of MBP.
5.We made model mice of spinal cord injury. The number of survived axons was significantly more in neuropsin knockout mice than wild type.
The above results indicate that these two proteases are expressed in oligodendrocytes after injury and are involved in demyelination.
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