Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination
Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination
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DOI：
10.1002/cne.10934
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发表时间：
2003-12-15
影响因子：
2.5
通讯作者：
Tuszynski, MH
中科院分区：
文献类型：
--
作者：
Blesch, A;Tuszynski, MH
胶质细胞系源性神经营养因子 (GDNF) 是生长因子家族的典型成员，通过同源受体 ret 和 GDNF 受体 α-1 发出信号。后一种受体在投射到脊髓的各种神经元上表达，包括脊髓上神经元、背根神经节和局部神经元。尽管 GDNF 对大脑神经元存活的影响之前已有报道，但 GDNF 对成人脊髓受损轴突的影响尚未得到研究。使用为轴突生长提供营养支持和细胞基质的离体基因递送方法，我们将经过基因改造以分泌 GDNF 的原代成纤维细胞植入完全和部分中胸脊髓横断位点。与表达报告基因的对照移植物的接受者相比，表达GDNF的移植物促进了多个脊柱系统的显着再生，包括背柱感觉、区域突出的本体脊髓和局部运动轴突。局部 GDNF 表达还诱导施万细胞迁移到病变部位，导致再生轴突的髓鞘再生。因此，GDNF 对成人脊髓轴突和雪旺细胞发挥热带作用，有助于损伤后轴突的生长。 (C) 2003 Wiley-Liss, Inc.
Glial cell line-derived neurotrophic factor (GDNF) is the prototypical member of a growth factor family that signals via the cognate receptors ret and GDNF-receptor alpha-1. The latter receptors are expressed on a variety of neurons that project into the spinal cord, including supraspinal neurons, dorsal root ganglia, and local neurons. Although effects of GDNF on neuronal survival in the brain have previously been reported, GDNF effects on injured axons of the adult spinal cord have not been investigated. Using an ex vivo gene delivery approach that provides both trophic support and a cellular substrate for axonal growth, we implanted primary fibroblasts genetically modified to secrete GDNF into complete and partial mid-thoracic spinal cord transection sites. Compared to recipients of control grafts expressing a reporter gene, GDNF-expressing grafts promoted significant regeneration of several spinal systems, including dorsal column sensory, regionally projecting propriospinal, and local motor axons. Local GDNF expression also induced Schwann cell migration to the lesion site, leading to remyelination of regenerating axons. Thus, GDNF exerts tropic effects on adult spinal axons and Schwann cells that contribute to axon growth after injury. (C) 2003 Wiley-Liss, Inc.