Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation.
Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation.
复制标题
GDNF 的过度表达诱导并维持肌纤维的过度神经支配和多个终板的形成。
DOI：
10.1006/exnr.2001.7753
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Davis,BM
中科院分区：
文献类型：
--
作者：
Zwick,M;Teng,L;Mu,X;Springer,JE;Davis,BM
本研究探讨了胶质细胞源性神经营养因子（GDNF）在发育中的神经肌肉接头突触可塑性中的作用。在肌球蛋白轻链-1启动子下在骨骼肌中过表达GDNF的转基因小鼠被分离。北方印迹和ELISA检测表明，GDNF转基因动物的腓肠肌外侧肌（LGM）中GDNF mRNA和蛋白水平升高了3倍。在6周龄的LGM组织切片的组织化学检查显示，胆碱酯酶阳性终板的数量增加了70%，而终板面积没有变化。在单个肌纤维上也观察到多个终板，除了多个轴突过程终止于单个终板。脊髓运动神经元的数量，整体LGM的大小，或肌肉类型的组成没有变化。最后，GDNF在肌肉中的过表达引起背根神经节中神经元胞体的肥大，而不影响它们的数量。这些研究结果表明，骨骼肌中的一个单一的神经营养因子的过度表达诱导多个终板的形成，并保持过度神经支配远远超过正常的发育期。我们认为GDNF是一种肌源性运动神经元神经营养因子，在发育和成年神经肌肉接头的突触可塑性调节中起重要作用。
This study examined the role of glial cell line-derived neurotrophic factor (GDNF) in synaptic plasticity at the developing neuromuscular junction. Transgenic mice overexpressing GDNF in skeletal muscle under the myosin light chain-1 promoter were isolated. Northern blot and ELISA at 6 weeks of age indicated that GDNF mRNA and protein levels were elevated threefold in the lateral gastrocnemius muscle (LGM) of the GDNF-transgenic animals. Histochemical examination of LGM tissue sections at 6 weeks of age revealed a 70% increase in the number of cholinesterase-positive end plates without changes in end-plate area. Multiple end plates on a single muscle fiber were also observed, in addition to multiple axonal processes terminating on individual end plates. No change in the number of spinal motoneurons, overall LGM size, or muscle type composition was observed. Finally, overexpression of GDNF in muscle caused hypertrophy of neuronal somata in dorsal root ganglia without affecting their number. These findings demonstrate that overexpression of a single neurotrophic factor in skeletal muscle induces multiple end-plate formation and maintains hyperinnervation well beyond the normal developmental period. We suggest that GDNF, a muscle-derived motoneuron neurotrophic factor, serves an important role in the regulation of synaptic plasticity in the developing and adult neuromuscular junction.