Target-derived trophic effect on skeletal muscle innervation in senescent mice

被引:50
作者
Messi, ML
Delbono, O
机构
[1] Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA
[2] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA
[3] Wake Forest Univ, Sch Med, Program Neurosci, Winston Salem, NC 27157 USA
关键词
target-derived trophic effect; IGF-1; aging; neuromuscular junction; skeletal muscle; innervation; denervation; mouse;
D O I
10.1523/JNEUROSCI.23-04-01351.2003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the present work, we tested the hypothesis that target-derived insulin-like growth factor-1 (IGF-1) prevents alterations in neuromuscular innervation in aging mammals. To explore this hypothesis, we studied senescent wild-type mice as a model of deficient IGF-1 secretion and signaling and S1S2 transgenic mice as a tool to investigate the role of sustained overexpression of IGF-1 in striated muscle in neuromuscular innervation. The analysis of the nerve terminal in extensor digitorum longus muscles from senescent mice showed that the decrease in the percentage of cholinesterase-stained zones (CSZ) exhibiting nerve terminal branching, number of nerve branches at the CSZ, and nerve branch points was partially or completely reversed by sustained overexpression of IGF-1 in skeletal muscle. Target-derived IGF-1 also prevented age-related decreases in the postterminal alpha-bungarotoxin immunostained area, as well as the reduction in the number and length of postsynaptic folds, and area and density of postsynaptic folds studied with electron microscopy. Overexpression of IGF-1 in skeletal muscle may account for the lack of age-dependent switch in muscle fiber type composition recorded in senescent mice. In summary, the use of the S1S2 IGF-1 transgenic mouse model allowed us to provide morphological evidence for the role of target-derived IGF-1 in spinal cord motor neurons in senescent mice.
引用
收藏
页码:1351 / 1359
页数:9
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