Promotion of Neuronal Guidance Growth by Aminated Graphene Oxide via Netrin-1/Deleted in Colorectal Cancer Signaling.,ACS Chemical Neuroscience

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Promotion of Neuronal Guidance Growth by Aminated Graphene Oxide via Netrin-1/Deleted in Colorectal Cancer Signaling.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-02-10 , DOI: 10.1021/acschemneuro.9b00625
Meili Liu _{1,

2} , Chongquan Huang _{1,

2} , Zhengtai Jia _{1,

2} , Zhijun Zhao _{1,

2} , Xiongfu Xiao _{1,

2} , Anqing Wang _{1,

2} , Ping Li _{1,

2} , Xiali Guan _{1,

2} , Gang Zhou _{1,

2,

3} , Yubo Fan _{1,

2,

3,

4}

Affiliation

Promotion of neurite outgrowth and synapse formation is a key step for nervous tissue regeneration. It is important for finding a new biomaterial to guide neuron growth to target neurons. Aminated graphene oxide (NH2-GO) displays electrical properties and dispersibility, which may change the surface charge of neurons and further activate neuronal excitement. However, the molecular guidance mechanism of NH2-GO on neurite outgrowth is seldom reported. In this study, we compared the role of NH2-GO on the spinal cord neurons and cortical neurons. Results indicated that the proper concentrations were at 2 and 4 μg/mL as determined by the CCK-8 assay. Notably, NH2-GO (2 and 4 μg/mL) improved the dispersibility and strengthened the effect of the composite material. In addition, it enables biocompatibility and efficient guidance of growth performance, which is not neurotoxic for neuronal outgrowth under these two concentrations. More interestingly, NH2-GO at 2 μg/mL induced both marked neurite elongation and increased branches in cortical neurons, but there is no significant change of neurite length and branches in spinal cord neurons. Further, the fluorescence intensity and mRNA level of Netrin-1 and DCC (Deleted in Colorectal Cancer) were both enhanced by NH2-GO at 2 μg/mL. Moreover, the function of Netrin-1 and DCC were activated more significantly by NH2-GO at 2 μg/mL in cortical neurons than that of spinal cord neurons. When RhoA was inhibited by the C3 exoenzyme, phosphorylated Rac1 and Cdc42 expression decreased significantly. Thus, NH2-GO at 2 μg/mL could influence Netrin-1/DCC signaling and the downstream RhoGTPase pathway, which may be preferred to guide the neurite growth in cortical neurons. It will provide a promising approach for the development of novel therapeutic methods of nerve regeneration.

中文翻译：

通过Netrin-1 /胺化氧化石墨烯促进神经元引导生长-在结直肠癌信号中删除。

促进神经突生长和突触形成是神经组织再生的关键步骤。寻找一种新的生物材料以指导神经元生长以靶向神经元很重要。胺化氧化石墨烯（NH2-GO）具有电性能和分散性，可改变神经元的表面电荷并进一步激活神经元兴奋。然而，很少报道NH2-GO对神经突生长的分子指导机制。在这项研究中，我们比较了NH2-GO在脊髓神经元和皮层神经元中的作用。结果表明，通过CCK-8分析测定，合适的浓度为2和4μg/ mL。值得注意的是，NH2-GO（2和4μg/ mL）提高了分散性并增强了复合材料的效果。此外，它还可以实现生物相容性和对生长性能的有效指导，在这两个浓度下，它对神经元的生长没有神经毒性。更有趣的是，浓度为2μg/ mL的NH2-GO既能诱导明显的神经突伸长，又能增加皮层神经元的分支，但脊髓神经元的神经突长度和分支没有明显变化。此外，NH2-GO以2μg/ mL的浓度增强了Netrin-1和DCC（在结直肠癌中已删除）的荧光强度和mRNA水平。此外，皮层神经元中2 ug / mL的NH2-GO比脊髓神经元更显着地激活Netrin-1和DCC的功能。当RhoA被C3外切酶抑制时，磷酸化的Rac1和Cdc42表达显着下降。因此，浓度为2μg/ mL的NH2-GO可能会影响Netrin-1 / DCC信号传导和下游RhoGTPase途径，它可能是指导皮层神经元神经突生长的首选方法。这将为神经再生的新型治疗方法的发展提供有希望的方法。

更新日期：2020-02-10

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