Potential effect of mechano growth factor E-domain peptide on axonal guidance growth in primary cultured cortical neurons of rats
Potential effect of mechano growth factor E-domain peptide on axonal guidance growth in primary cultured cortical neurons of rats
复制标题
机械生长因子E结构域肽对原代培养的大鼠皮层神经元轴突引导生长的潜在影响
DOI：
10.1002/term.2364
复制
发表时间：
2018
影响因子：
3.3
通讯作者：
Fan Yubo
中科院分区：
文献类型：
--
作者：
Liu Meili;Niu Xufeng;Zhou Gang;Jia Zhengtai;Li Ping;Fan Yubo
建立适当的突触连接和可塑性是神经元再生和发育的关键需要。机械生长因子（Mechano growth factor， MGF）及其含有24个氨基酸的C末端E结构域肽MGF - Ct24E是潜在的神经保护剂。我们的初步研究表明，Netrin‐1可以引导轴突生长，其表达对MGF敏感，但MGF如何调节Netrin‐1及其受体DCC的表达尚不清楚。在此，我们研究了MGF - Ct24E对体外原代培养皮层神经元素和体内成年大鼠脑中Netrin - 1和DCC表达的影响。MTT实验表明，MGF - Ct24E能显著保护原代皮质神经元免受神经损伤。0.5和1.0 μg/ml浓度的MGF - Ct24E处理后，轴突伸长显著增加。实时聚合酶链反应实验表明，MGF - Ct24E能有效促进原代培养皮层神经元中Netrin - 1和DCC的表达。为了确定MGF - Ct24E对神经元引导和生长的作用机制，我们在创伤性脑损伤后给成年大鼠肌肉注射MGF - Ct24E。注射MGF - Ct24E的大鼠在14天内开始进食和饮水，表明MGF - Ct24E可以促进康复。脑切片HE染色和免疫组化分析显示，MGF - Ct24E处理能显著抑制外伤性脑损伤出血，促进Netrin - 1的表达。Western blot进一步研究MGF - Ct24E对神经损伤后Netrin - 1和DCC的表达有促进作用。MGF - Ct24E可以通过上调Netrin - 1/DCC信号，有效改善神经元再生过程中的轴突引导。版权所有©2016 John Wiley & Sons， Ltd。
Establishing appropriate synaptic connections and plasticity is a critical need in neuronal regeneration and development. Mechano growth factor (MGF) and its C‐terminal E‐domain peptide with 24 amino acids, MGF‐Ct24E, are potential neuroprotective agents. Our preliminary study indicates that Netrin‐1 can guide axonal growth and its expression is sensitive to MGF, but how MGF regulates the expression of Netrin‐1 and its receptor DCC is still unclear. Here, we investigate the effect of MGF‐Ct24E on the expression of Netrin‐1 and DCC in primary cultured cortical neuronsin vitroand the adult rat brainin vivo. MTT assay shows that MGF‐Ct24E can significantly protect primary cortical neurons against nerve injury. There is a significant increase in axonal elongation after MGF‐Ct24E treatment at concentrations of 0.5 and 1.0 μg/ml. Real‐time polymerase chain reaction assay indicates that MGF‐Ct24E can effectively promote the expression of Netrin‐1 and DCC in primary cultured cortical neurons. To identify the certain mechanism of MGF‐Ct24E on neuronal guidance and growth, adult rats are subjected to intramuscular injection of MGF‐Ct24E after traumatic brain injury. Rats injected with MGF‐Ct24E start eating and drinking within 14 days, indicating that MGF‐Ct24E can promote rehabilitation. HE staining and immunohistochemistry assays of brain section slices reveal that MGF‐Ct24E treatment can significantly inhibit the haemorrhage of traumatic brain injury and promote expression of Netrin‐1. Further investigation of protein expression by Western blot assay shows that MGF‐Ct24E promotes expression of Netrin‐1 and DCC after nerve injury. MGF‐Ct24E can effectively improve axonal guidance through upregulation of Netrin‐1/DCC signalling in neuronal regeneration. Copyright © 2016 John Wiley & Sons, Ltd.