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石墨烯通过局部阻断神经生长因子信号内体促进轴突伸长。

Graphene Promotes Axon Elongation through Local Stall of Nerve Growth Factor Signaling Endosomes.

机构信息

NEST, Scuola Normale Superiore, 56127 Pisa, Italy.

Center for Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, 56127 Pisa, Italy.

出版信息

Nano Lett. 2020 May 13;20(5):3633-3641. doi: 10.1021/acs.nanolett.0c00571. Epub 2020 Apr 13.

Abstract

Several works reported increased differentiation of neuronal cells grown on graphene; however, the molecular mechanism driving axon elongation on this material has remained elusive. Here, we study the axonal transport of nerve growth factor (NGF), the neurotrophin supporting development of peripheral neurons, as a key player in the time course of axonal elongation of dorsal root ganglion neurons on graphene. We find that graphene drastically reduces the number of retrogradely transported NGF vesicles in favor of a stalled population in the first 2 days of culture, in which the boost of axon elongation is observed. This correlates with a mutual charge redistribution, observed via Raman spectroscopy and electrophysiological recordings. Furthermore, ultrastructural analysis indicates a reduced microtubule distance and an elongated axonal topology. Thus, both electrophysiological and structural effects can account for graphene action on neuron development. Unraveling the molecular players underneath this interplay may open new avenues for axon regeneration applications.

摘要

已有多项研究报道,在石墨烯上培养的神经元细胞分化能力增强;然而,促使神经元轴突在该材料上延伸的分子机制仍难以捉摸。在这里,我们研究了神经生长因子(NGF)的轴突运输,NGF 是支持外周神经元发育的神经营养因子,作为背根神经节神经元在石墨烯上轴突延伸时间过程中的关键因素。我们发现,石墨烯极大地减少了逆行运输的 NGF 囊泡数量,有利于培养的前 2 天中囊泡的停滞,在此期间观察到轴突的延伸增加。这与通过拉曼光谱和电生理记录观察到的相互电荷再分配相关。此外,超微结构分析表明微管距离减小,轴突拓扑结构延长。因此,电生理和结构效应都可以解释石墨烯对神经元发育的作用。揭示这种相互作用下的分子机制可能为轴突再生应用开辟新途径。

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