An Increase in Membrane Cholesterol by Graphene Oxide Disrupts Calcium Homeostasis in Primary Astrocytes

Abstract

GNMs for neurological applications, however, requires a detailed knowledge of the impact of such materials on the biology of the various CNS cell populations. The impact of GNMs on the morphological and functional properties of primary neurons has been extensively described. [3][4][5][6] Conversely, a detailed description of the biological interactions between GNMs and glial cells has not been fully addressed yet.Among the various glial subtypes populating the CNS, astrocytes represent 20-40% of cells. [7] Astrocytes actively contribute to the activity of neural circuits by controlling the dynamics of the perineuronal milieu through their capacity to maintain the extracellular ion and neurotransmitter homeostasis. [8,9] Moreover, astrocytes are involved in the structural remodeling of neural networks by directing synapse formation and pruning, regulating brain metabolism, and participating in the neurovascular coupling. [10,11] Many of these functions are mediated by dynamic variations in intracellular calcium levels ([Ca 2+ ] i ), which follow the paracrine activation of metabotropic receptors by signaling molecules released from cells of neuronal, glial, and vascular origin. [12] Of note, alterations of astroglial [Ca 2+ ] i dynamics are observed under several central nervous 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, the molecular changes induced in cortical astrocytes by few-layer graphene (FLG) and graphene oxide (GO) flakes are addressed. The results show that exposure to FLG/GO does not affect cell viability or proliferation. However, proteomic and lipidomic analyses unveil alterations in several cellular processes, including intracellular Ca 2+ ([Ca 2+] i ) homeostasis and cholesterol metabolism, which are particularly intense in cells exposed to GO. Indeed, GO exposure impairs spontaneous and evoked astrocyte [Ca 2+ ] i signals and induces a marked increase in membrane cholesterol levels. Importantly, cholesterol depletion fully rescues [Ca 2+ ] i dynamics in GO-treated cells, indicating a causal relationship between these GO-mediated effects. The results indicate that exposure to GNMs alters intracellular signaling in astrocytes and may impact astrocyte-neuron interactions. Graphene NanomaterialsThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

Hydrogenated Graphene Improves Neuronal Network Maturation and Excitatory Transmission

“…[ 32 ] Similarly, this hypothesis holds also for the improved interactions between neurons and astrocytes with pristine Gr, GO, and rGO. [ 27,28,74 ]…”

“…[32] Similarly, this hypothesis holds also for the improved interactions between neurons and astrocytes with pristine Gr, GO, and rGO. [27,28,74] We finally analyzed the PET-supported samples used in our assay to evaluate the effect of the neurons on the underlying graphene materials. Figure S6, Supporting Information, shows the Raman spectra taken on PET/Gr and PET/HGr samples, as detailed in the Experimental Section.…”

“…[ 18,19 ] Graphene has already been used as a flexible implant for in vitro and in vivo recordings, [ 20,21 ] field‐effect transistors (FETs) for signal amplification of neural activity in vitro and in vivo, [ 22,23 ] superficial coating to foster neuronal growth and development, [ 24–26 ] and to target neuronal excitability. [ 27–31 ]…”

“…[18,19] Graphene has already been used as a flexible implant for in vitro and in vivo recordings, [20,21] field-effect transistors (FETs) for signal amplification of neural activity in vitro and in vivo, [22,23] superficial coating to foster neuronal growth and development, [24][25][26] and to target neuronal excitability. [27][28][29][30][31] In an ideal neuron-friendly interface, high wettability and electrical conductivity are both required. [32,33] Pristine graphene presents high electrically conductivity but low wettability (i.e., showing a water contact angle >90° when supported on most substrates of interest), [34,35] and this can partially limit its biological applications.…”

Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction

“…Along the same line of work, the preparation and exploitation of two GFs with different stiffness as neural interfacing scaffolds has been investigated, including the effect of GF mechanical properties on different parameters of neural cell physiology. [122] It has been highlighted as stiffer scaffold could boost neural stem cells adhesion, growth, and differentiation toward astrocytes compared to the softer substrates.…”