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Graphene-based materials are the focus of intense research efforts to devisenovel theranostic strategies for targeting the central nervous system. In thiswork, we have investigated the consequences of long-term exposure of primaryrat astrocytes to pristine graphene (GR) and graphene oxide (GO) flakes. Wedemonstrate that GR/GO interfere with a variety of intracellular processes as aresult of their internalization through the endo-lysosomal pathway.Graphene-exposed astrocytes acquire a more differentiated morphologicalphenotype associated with extensive cytoskeletal rearrangements. Profoundfunctional alterations are induced by GO internalization, including theupregulation of inward-rectifying K+ channels and of Na+-dependent glutamateuptake, which are linked to the astrocyte capacity to control the extracellularhomeostasis. Interestingly, GO-pretreated astrocytes promote the functionalmaturation of co-cultured primary neurons by inducing an increase in intrinsicexcitability and in the density of GABAergic synapses. The results indicatethat graphene nanomaterials profoundly affect astrocyte physiology in vitro,with consequences for neuronal network activity. This work supports the viewthat GO-based materials could be of great interest to address pathologies ofthe central nervous system associated to astrocyte dysfunctions.

Graphene oxide upregulates the homeostatic functions of primary astrocytes and modulates astrocyte-to-neuron communication