| Project/Area Number |
16390433
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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 |
Orthopaedic surgery
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| Research Institution | Research Institute, National Rehabilitation Center |
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Principal Investigator |
YAMAMOTO Shinichi Research Institute, National Rehabilitation Center, Division of Motor Dysfunction, Chief Researcher, 運動機能系障害研究部, 主任研究官 (30282560)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Sakae The University of Tokyo, University Hospital, Assistant Professor, 医学部付属病院, 講師 (50282661)
SEICHI Atsushi The University of Tokyo, University Hospital, Assistant Professor, 医学部付属病院, 講師 (70236066)
NAKAMURA Kozo The University of Tokyo, University Hospital, Professor, 医学部付属病院, 教授 (60126133)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | spinal cord injury / oligodendrocyte / precursor cells / primary culture / differentiation / gene transfer |
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| Research Abstract |
Spinal cord injury is one of the most severe trauma in central nervous systems, resulting several thousand new patients every year. From the view point of innovating new therapeutic approach for this injury, the proper control of "Glial Scar" is very important because the scar is believed to interrupt regenerating axons. In peripheral nervous systems, which can regenerate after injury, Schwann cells, myelinating cell in peripheral nerve, proliferate after injury and they occupy the damaged area. The regenerating axons go though "Schwann cell packed area". Therefore, we put focus on controlling oligodendrocyte precursor cells, myelinating cells in central nervous systems, so that they occupy the damaged area in spinal cord and help regenerating axons.
In this research project, we first worked on the establishment of primary culture of mouse oligodendrocyte, which enable us to reveal molecular function by in vitro experiments. Oligodendrocytes are known to proliferate in immature form if
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the culture condition contain enough growth factors. It is not known whether growth factors convey any specific effect to keep the cells in immature status. From the protein expression analysis, we chose Cyclin D1 molecule, well known cell cycle promoting molecule, because its protein level shows strong correlation with immature status of oligodendrocyte. Molecular function of Cyclin D1 on oligodendrocyte maturation is investigated by cloning Cyclin D1, generating mutant forms of the molecule, gene transfer to the cells and analyzing differentiation markers. We found that Cyclin D1 has distinct mechanism to control oligodendrocyte maturation apart from its cell-cycle regulating function. For the future studies, we are planning to introduce these finding to animal model of spinal cord injury to see whether we can control proliferating oligodendrocyte in after spinal cord injury and prevent glial scar formation.
We also perform DNA microarray analysis to survey the molecules which is relevant to immature status of oligodendrocyte. Our primary culture of mouse oligodendrocyte is helpful and we could identified 20 genes which is possibly related to oligodendrocyte maturation. We are planning to explore molecular function of each molecules in the future. Less
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