| Project/Area Number |
20591738
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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 |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
WAKABAYASHI Yoshiaki Tokyo Medical and Dental University, 大学院・医歯学総合研究科, 助教 (00431916)
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| Co-Investigator(Renkei-kenkyūsha) |
ITO Soichiro 国際医療福祉大学, 保健医療学部, 教授 (10242190)
ENOMOTO Mitsuhiro 東京医科歯科大学, 医歯学総合研究科, 寄付講座講師 (90451971)
SHINOMIYA Kenichi 東京医科歯科大学, 医歯学総合研究科, 名誉教授 (20111594)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 神経再生 / 低分子G蛋白質 / 末梢神経 / 組換えアデノウイルス |
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| Research Abstract |
It is known that Rho family small GTPases activate a number of signal transduction pathways involved in cell cycle progression, gene expression, and cell survival. These small G proteins play an important role in neuronal survival and axon regeneration in neural injury. In this study, we tested whether the activity of RhoA or Rac1 regulates neurite extension in dorsal root ganglia (DRGs) in vitro and nerve regeneration in injured sciatic nerves. Regeneration of neurites from explanted DRGs was accelerated by combined suppression of RhoA and Rac1 activity using adenoviruses expressing dominant negative (DN) forms of both RhoA and Rac1 (Ad-Rho/RacDN) in vitro. Rat sciatic nerves were cut and Ad-Rho/RacDN was injected into the proximal stumps. After bridge grafting with chitosan mesh tubes, muscle evoked potentials induced by transcranial electrical stimulation were recorded eight weeks postoperatively. The terminal latencies were shorter in the Ad-Rho/RacDN group than in the control group. Histological analysis revealed extensive regrowth of neurofilament-positive and myelinated axons within the tubes in the group that received Ad-Rho/RacDN. These findings suggest that combined regulation of RhoA and Rac1 using DN adenoviral transgenic methods has the potential to modify injured peripheral nerve tissues directly.
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