Departamento de Química Orgánica , Universidad de Castilla La-Mancha , 13071 Ciudad Real , Spain.
Department of Pharmacy and Biotechnology , University of Bologna , 40126 Bologna , Italy.
Nano Lett. 2018 Sep 12;18(9):5827-5838. doi: 10.1021/acs.nanolett.8b02487. Epub 2018 Aug 15.
Graphene-based materials are the focus of intense research efforts to devise novel theranostic strategies for targeting the central nervous system. In this work, we have investigated the consequences of long-term exposure of primary rat astrocytes to pristine graphene (GR) and graphene oxide (GO) flakes. We demonstrate that GR/GO interfere with a variety of intracellular processes as a result of their internalization through the endolysosomal pathway. Graphene-exposed astrocytes acquire a more differentiated morphological phenotype associated with extensive cytoskeletal rearrangements. Profound functional alterations are induced by GO internalization, including the upregulation of inward-rectifying K channels and of Na-dependent glutamate uptake, which are linked to the astrocyte capacity to control the extracellular homeostasis. Interestingly, GO-pretreated astrocytes promote the functional maturation of cocultured primary neurons by inducing an increase in intrinsic excitability and in the density of GABAergic synapses. The results indicate that graphene nanomaterials profoundly affect astrocyte physiology in vitro with consequences for neuronal network activity. This work supports the view that GO-based materials could be of great interest to address pathologies of the central nervous system associated with astrocyte dysfunctions.
基于石墨烯的材料是设计针对中枢神经系统的新型治疗策略的研究重点。在这项工作中，我们研究了原石墨烯（GR）和氧化石墨烯（GO）薄片对原代大鼠星形胶质细胞长期暴露的后果。我们证明 GR/GO 通过内吞作用进入细胞内体途径，干扰多种细胞内过程。暴露于石墨烯的星形胶质细胞获得与广泛的细胞骨架重排相关的更分化的形态表型。GO 的内化诱导了深刻的功能改变，包括内向整流钾通道和 Na 依赖性谷氨酸摄取的上调，这与星形胶质细胞控制细胞外稳态的能力有关。有趣的是，GO 预处理的星形胶质细胞通过增加内在兴奋性和 GABA 能突触的密度来促进共培养的原代神经元的功能成熟。结果表明，石墨烯纳米材料在体外显著影响星形胶质细胞的生理学，从而影响神经元网络的活性。这项工作支持这样一种观点，即基于 GO 的材料可能对解决与星形胶质细胞功能障碍相关的中枢神经系统疾病具有重要意义。
