A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury.
A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury.
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DOI：
10.1523/jneurosci.2973-12.2013
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发表时间：
2013-03-27
期刊：
影响因子：
--
通讯作者：
Xu XM
中科院分区：
文献类型：
--
作者：
Deng LX;Deng P;Ruan Y;Xu ZC;Liu NK;Wen X;Smith GM;Xu XM
下行脊髓本体神经元（DPSN）被认为是建立脊髓上信号的功能中继，并且它们在损伤后比长的投射轴突表现出更大的生长反应。然而，它们的再生反应仍然是不足的，这是由于它们未能离开生长支持细胞移植回到宿主脊髓中，其中包含许多轴突生长的障碍。在这里，我们报告了一个连续的生长促进途径的建设，在成年大鼠，形成移植的雪旺细胞（SC）过表达胶质细胞源性神经营养因子（GDNF）。我们证明，这样的生长促进途径，从轴突切断端延伸到远端脊髓的神经支配部位，促进DPSN轴突再生通过和超越脊髓半切损伤间隙。在远端宿主脊髓内，再生的DPSN轴突与宿主神经元形成突触，导致动作电位的恢复和功能的部分恢复。
Descending propriospinal neurons (DPSN) are known to establish functional relays for supraspinal signals, and they display a greater growth response after injury than do the long projecting axons. However, their regenerative response is still deficient due to their failure to depart from growth supportive cellular transplants back into the host spinal cord, which contains numerous impediments to axon growth. Here we report the construction of a continuous growth-promoting pathway in adult rats, formed by grafted Schwann cells (SCs) overexpressing glial cell line-derived neurotrophic factor (GDNF). We demonstrate that such a growth-promoting pathway, extending from the axonal cut ends to the site of innervation in the distal spinal cord, promoted regeneration of DPSN axons through and beyond the lesion gap of a spinal cord hemisection. Within the distal host spinal cord, regenerated DPSN axons formed synapses with host neurons leading to the restoration of action potentials and partial recovery of function.