Resveratrol Enhances Neurite Outgrowth and Synaptogenesis Via Sonic Hedgehog Signaling Following Oxygen-Glucose Deprivation/Reoxygenation Injury
Resveratrol Enhances Neurite Outgrowth and Synaptogenesis Via Sonic Hedgehog Signaling Following Oxygen-Glucose Deprivation/Reoxygenation Injury
复制标题
白藜芦醇 - 在缺氧/复氧损伤后通过 Sonic Hedgehog 信号传导增强神经突生长和突触发生
DOI：
10.1159/000481611
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Yang, Qin
中科院分区：
文献类型：
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作者：
Tang, Fanren;Guo, Shuang;Yang, Qin
背景/目的：神经突起生长和突触发生是卒中后功能恢复的关键步骤。白藜芦醇促进神经突起生长和突触发生，但其潜在机制尚不清楚，尽管可能涉及Sonic hedgehog（Shh）信号通路。鉴于白藜芦醇激活sirtuin（Sirt）1，本研究探讨了这是否由Shh信号传导介导。方法：原代培养的皮层神经元在氧糖剥夺/复氧（OGD/R）前用药物预处理。分别用细胞计数试剂盒8和末端脱氧核苷酸转移酶dUTP缺口末端标记法评价细胞活力和凋亡。通过免疫细胞化学和蛋白质印迹法评估神经突起生长和突触发生，这也用于检查Sirt 1和Shh信号蛋白的表达。结果如下：白藜芦醇和Smoothened（Smo）激动剂purmophamine，可激活Shh信号传导，增加活力，减少凋亡，并刺激OGD/R损伤后的神经突生长。此外，生长相关蛋白（GAP）-43，synaptophysin，Shh，Patched（Ptc）-1，Smo，胶质瘤相关癌基因同源物（Gli）-1，Sirt 1的表达在这些条件下上调。这些影响被逆转的Smo抑制剂cyclopamine治疗，而Sirt 1抑制剂sirtinol降低了Shh，Ptc-1，Smo和Gli-1的水平。结论：白藜芦醇可减少OGD/R损伤后的神经元损伤，并通过激活Shh信号通路促进神经突起生长和突触发生，进而诱导Sirt 1。(c)2017作者（s）由S. Karger AG，巴塞尔
Background/Aims: Neurite outgrowth and synaptogenesis are critical steps for functional recovery after stroke. Resveratrol promotes neurite outgrowth and synaptogenesis, but the underlying mechanism is not well understood, although the Sonic hedgehog (Shh) signaling pathway may be involved. Given that resveratrol activates sirtuin (Sirt)1, the present study examined whether this is mediated by Shh signaling. Methods: Primary cortical neuron cultures were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R). Cell viability and apoptosis were evaluated with Cell Counting Kit 8 and by terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Neurite outgrowth and synaptogenesis were assessed by immunocytochemistry and western blotting, which was also used to examine the expression of Sirt1 and Shh signaling proteins. Results: Resveratrol and the Smoothened (Smo) agonist purmophamine, which activates Shh signaling, increased viability, reduced apoptosis, and stimulated neurite outgrowth after OGD/R injury. Moreover, the expression of growth-associated protein(GAP)-43, synaptophysin, Shh, Patched (Ptc)-1, Smo, glioma-associated oncogene homolog (Gli)-1, and Sirt1 were upregulated under these conditions. These effects were reversed by treatment with the Smo inhibitor cyclopamine, whereas the Sirt1 inhibitor sirtinol reduced the levels of Shh, Ptc-1, Smo, and Gli-1. Conclusions: Resveratrol reduces neuronal injury following OGD/R injury and enhances neurite outgrowth and synaptogenesis by activating Shh signaling, which in turn induces Sirt1. (c) 2017 The Author(s) Published by S. Karger AG, Basel