  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 endo-lysosomal 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 co-cultured 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 to astrocyte dysfunctions.

Neurons and Cognition;Cell Behavior