An increase in membrane cholesterol by graphene oxide disrupts calcium homeostasis in primary astrocytes

TL;DR

This study reveals that graphene oxide increases membrane cholesterol in astrocytes, disrupting calcium signaling, which could affect neuron-astrocyte interactions, highlighting potential neurobiological impacts of graphene nanomaterials.

Contribution

It demonstrates that graphene oxide exposure elevates membrane cholesterol and impairs calcium homeostasis in astrocytes, revealing a novel molecular mechanism of GNM effects on brain cells.

Findings

GO increases membrane cholesterol levels in astrocytes.

Cholesterol depletion rescues calcium signaling disruptions.

GNMs alter intracellular signaling pathways in brain cells.

Abstract

The use of graphene nanomaterials (GNMs) for biomedical applications targeted to the central nervous system is exponentially increasing, although precise information on their effects on brain cells is lacking. In this work, we addressed the molecular changes induced in cortical astrocytes by few-layer graphene (FLG) and graphene oxide (GO) flakes. Our results show that exposure to FLG/GO does not affect cell viability or proliferation. However, proteomic and lipidomic analyses unveiled alterations in several cellular processes, including intracellular Ca2+ ([Ca2+]i) homeostasis and cholesterol metabolism, which were particularly intense in cells exposed to GO. Indeed, GO exposure impaired spontaneous and evoked astrocyte [Ca2+]i signals and induced a marked increase in membrane cholesterol levels. Importantly, cholesterol depletion fully rescued [Ca2+]i dynamics in GO-treated cells, indicating a causal relationship between these GO-mediated effects. Our results indicate that exposure to GNMs alters intracellular signaling in astrocytes and may impact on astrocyte-neuron interactions.