Graphene Oxide Nanosheets Reshape Synaptic Function in Cultured Brain Networks

Abstract

Graphene offers promising advantages for biomedical applications. However, adoption of graphene technology in biomedicine also poses important challenges in terms of understanding cell responses, cellular uptake, or the intracellular fate of soluble graphene derivatives. In the biological microenvironment, graphene nanosheets might interact with exposed cellular and subcellular structures, resulting in unexpected regulation of sophisticated biological signaling. More broadly, biomedical devices based on the design of these 2D planar nanostructures for interventions in the central nervous system require an accurate understanding of their interactions with the neuronal milieu. Here, we describe the ability of graphene oxide nanosheets to down-regulate neuronal signaling without affecting cell viability.

Graphene Oxide Nanosheets Disrupt Lipid Composition, Ca2+ Homeostasis, and Synaptic Transmission in Primary Cortical Neurons

“…While the present paper was under revision, a similar paper confirming the impairment of excitatory transmission by GO was published. 65…”

Graphene Oxide Upregulates the Homeostatic Functions of Primary Astrocytes and Modulates Astrocyte-to-Neuron Communication

“…[3][4][5][6] However, recent studies reported that acute and chronic exposure of primary hippocampal and cortical neurons to graphene oxide (GO) caused altered Ca 2+ dynamics and an excitatory/inhibitory imbalance in favor of inhibitory synaptic transmission. 7,8 Astrocytes, which are the most numerous cell population in the mammalian CNS, are involved in the structural and functional regulation of neuronal circuits and contribute to maintain the homeostasis of the perineuronal milieu through the expression of specific ion channels and transporters. 9 Astrocytes respond to pathological insults in vivo by changing some of their molecular and functional features, a process called 'reactive astrocytosis', 10 which can be beneficial or detrimental to the integrity and functionality of neuronal circuits depending on the specific pathological setting.…”

Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36

“…Transients were expressed as ΔF/F 0 , the amplitude fractional increase, where ΔF is the fluorescence rise over baseline, and F 0 the baseline fluorescence level; [Ca 2+ ] i elevations were considered significant when they exceeded five times the noise S.D. 66, 67 …”