| Project/Area Number |
09670109
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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 |
General pharmacology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
SUZUKI Hidenori Nippon Medical School, Department of Pharmacology, Associate professor, 医学部, 助教授 (30221328)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Axon / Motor neuron / Glial cell line-derived neurotrophic factor / Neuromuscular junction / Human skeletal muscle / lmmunohistochemical analysis / Neuromuscular disease / Target-derived neurotrophic factor / 有髄神経軸策 / ニワトリ胚肢芽 / 神経軸索 / 標的依存性 / 免疫組織化学 |
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| Research Abstract |
We performed the expression analysis of glial cell line-derived neurotrophic factor (GDNF) in adult human muscle by RNA blot and immunohistochemical analysis to address the physiological role of GDNF in humans. GDNF mRNA was highly expressed in the human skeletal muscle compared to that in the mouse skeletal muscle. Condensed immunoreactivity of GDNF was observed in the vicinity of plasma membranes of skeletal muscle and especially concentrated at neuromuscular junctions. The axons and surrounding Schwann cells of peripheral nerve bundles were also stained with the GDNF antibody. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed hat GDNF mRNA was amplified in the human muscle, but not in the anterior horn cells of the human spinal cord. These results suggest that GDNF is produced in the skeletal muscle, taken up by nerve terminals, and transported through the axons and might promote motor neuron survival as a target-derived neurotrophic factor.
We, then, examined expression of GDNF in muscles from neuromuscular diseases. Immunohistochemical analyses revealed that GDNF was up-regulated in regenerating fibers of polymyositis (PM) and Duchenne type muscular dystrophy (DMD). RT-PCR analyses showed that PM and DM0 muscles up-regulated the full length GDNF, meanwhile normal muscle exhibits mostly truncated GDNF.These results indicate that the GDNF expression is regulated in the regeneration of human skeletal muscle.
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