| Co-Investigator(Kenkyū-buntansha) |
KURAOKA Akio Kyushu University, Postgraduate School of Medicine, Lecturer, 医学研究院, 講師 (30253412)
HIRATA Kazuho Kyushu University, Postgraduate School of Medicine, Lecturer, 医学研究院, 講師 (00037425)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
We have already shown some age-related changes in regenerating NMJs, such as persistent damage in the terminal Schwann cell and the acetylcholine receptor (acetylcholine receptors, AChRs) region after sciatic nerve crushing injury. This research aimed at solving the relation of these changes and the signal mechanism. Cryostat sections of the soleus muscle were made, and first, after the composition element (axon, Schwann cell, AChR region) on NMJ was labeled, the expression of signal-related-substances (neuregulin (NRG), NRG receptors (erB2 and erB3) and glial cell line-derived neurotrophic factor (GDNF)) was double labeled by immunohistochemistry. Next, since NRG/erbB signaling is known to be concerned with the aggregation of AChRs, we examined the expression of dystrophin (DYS, postsynaptic cytoskeleton protein) in the AChR region as labeled by alpha-bungarotoxin. Observation was performed at the time when regeneration of NMJ was in progress (4-12 postoperative weeks).
Results. In the
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young animals NRG was distributed over the full length of regenerating axons, up to a growth cone or a terminal. ErB2 and erB3 of a NRG receptor were distributed over the synaptic folds and the terminal Schwann cells. Expression of NRG/erB2 (or erB3) became transiently increased at four postoperative week. GDNF was localized in the Schwann cell strands, and synaptic folds and terminal Schwann cells in the NMJ. Expression of GDNF was reinforced as regeneration progressed, and numerous NMJs showed the strong positivity at eight postoperative week. In the aged muscles any signal-related-substance (NRG, erB2, erB3, and GDNF) showed some abnormalities (delayed expression, weak staining, malformation). 2. Derangement in the distribution of a receptor region in aged animals frequently accompanied abnormalities in the expression of DYS (weak staining and partial lack). Conclusion. 1. The interaction between the presynaptic and postsynaptic region is important for regeneration or structural specialization of the NMJ, i.e., for recovery of a physiological function. It is thought that age-related abnormalities in the distribution of signal molecules reported here relate to the insufficiency of regeneration at the NMJs. 2. The old-age-model is useful in order to study the disturbance of the signal mechanism at NMJs. Less
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