Governor Vessel Electro-Acupuncture Promotes the Intrinsic Growth Ability of Spinal Neurons through Activating Calcitonin Gene-Related Peptide/alpha-Calcium/Calmodulin-Dependent Protein Kinase/Neurotrophin-3 Pathway after Spinal Cord Injury
Governor Vessel Electro-Acupuncture Promotes the Intrinsic Growth Ability of Spinal Neurons through Activating Calcitonin Gene-Related Peptide/alpha-Calcium/Calmodulin-Dependent Protein Kinase/Neurotrophin-3 Pathway after Spinal Cord Injury
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督脉电针通过激活脊髓损伤后降钙素基因相关肽/α-钙/钙调蛋白依赖性蛋白激酶/神经营养蛋白-3通路促进脊髓神经元的内在生长能力
DOI：
10.1089/neu.2020.7155
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发表时间：
2021
影响因子：
4.2
通讯作者：
Ding Ying
中科院分区：
文献类型：
--
作者：
Xu Haoyu;Yang Yang;Deng Qing-Wen;Zhang Bao-Bao;Ruan Jing-Wen;Jin Hui;Wang Jun-Hua;Ren Jiale;Jiang Bin;Sun Jia-Hui;Zeng Yuan-Shan;Ding Ying
脊髓损伤(SCI)往往导致神经元死亡和轴突再生失败。这主要归因于恶劣的微环境和损伤的脊髓神经元内在再生能力差。我们已报道电针督脉穴位可促进损伤脊髓神经元存活和轴突再生。然而，实现这一目标的潜在机制仍不确定。本研究旨在探讨GV-EA刺激的神经传入途径以及GV-EA激活损伤脊髓神经元内源性生长能力的可能机制。通过CTB逆行标记、免疫组织化学染色和ELISA法，我们发现GV-EA对背根神经节细胞的脊神经分支有刺激作用。这将增加降钙素基因相关肽(CGRP)从脊髓传入终末的释放；值得注意的是，这种作用在背根切断后被取消。另外，体内和体外实验结果均表明，降钙素基因相关肽通过激活降钙素基因相关肽/RAMP/αCaMKII通路，作用于突触后脊髓神经元，触发神经营养素-3(NT-3)的合成和分泌。值得注意的是，背根切断和CGRP/RAMP/αCaMKII通路的阻断剂可阻止观察到的效应。更重要的是，NT-3的增加促进了损伤脊髓神经元的存活、轴突再生和突触维持。结论：增加NT-3的产生是GV-EA激活脊髓损伤后脊髓神经元内源性生长能力的机制之一。实验结果为GV-EA治疗脊髓损伤的临床疗效提供了理论依据。
Spinal cord injury (SCI) invariably results in neuronal death and failure of axonal regeneration. This is attributed mainly to the hostile microenvironment and the poor intrinsic regrowth capacity of the injured spinal neurons. We have reported previously that electro-acupuncture on Governor Vessel acupoints (GV-EA) can promote neuronal survival and axonal regeneration of injured spinal cord. However, the underlying mechanism for this has remained uncertain. The present study aimed to explore the neural afferent pathway of GV-EA stimulation and the possible mechanism by which GV-EA can activate the intrinsic growth ability of injured spinal neurons. By CTB retrograde labeling, immunostaining and ELISA, we showed here that GV-EA could stimulate the spinal nerve branches of the dorsal root ganglion cells. This would then increase the release of calcitonin gene-related peptide (CGRP) from the afferent terminals in the spinal cord; of note, the effect was abrogated after dorsal rhizotomy. Additionally, both in vivo and in vitro results showed that CGRP would act on the postsynaptic spinal cord neurons and triggered the synthesis and secretion of neurotrophin-3 (NT-3) by activating the CGRP/RAMP1/αCaMKII pathway. Remarkably, the observed effect was prevented by the dorsal rhizotomy and the blockers of CGRP/RAMP1/αCaMKII pathway. More importantly, increase in NT-3 had promoted the survival, axonal regrowth and synaptic maintenance of spinal cord neurons in the injured spinal cord. Thus, it is concluded that increase in NT-3 production is one of the mechanisms by which GV-EA can activate the intrinsic growth ability of spinal neurons after SCI. The experimental results have reinforced the theoretical basis of GV-EA for its clinical efficacy in patients with SCI.