Tuning the Reduction of Graphene Oxide Nanoflakes Differently Affects Neuronal Networks in the Zebrafish

Abstract

The increasing engineering of biomedical devices and the design of drug-delivery platforms enriched by graphene-based components demand careful investigations of the impact of graphene-related materials (GRMs) on the nervous system. In addition, the enhanced diffusion of GRM-based products and technologies that might favor the dispersion in the environment of GRMs nanoparticles urgently requires the potential neurotoxicity of these compounds to be addressed. One of the challenges in providing definite evidence supporting the harmful or safe use of GRMs is addressing the variety of this family of materials, with GRMs differing for size and chemistry. Such a diversity impairs reaching a unique and predictive picture of the effects of GRMs on the nervous system. Here, by exploiting the thermal reduction of graphene oxide nanoflakes (GO) to generate materials with different oxygen/carbon ratios, we used a high-throughput analysis of early-stage zebrafish locomotor behavior to investigate if modifications of a specific GRM chemical property influenced how these nanomaterials affect vertebrate sensory-motor neurophysiology—exposing zebrafish to GO downregulated their swimming performance. Conversely, reduced GO (rGO) treatments boosted locomotor activity. We concluded that the tuning of single GRM chemical properties is sufficient to produce differential effects on nervous system physiology, likely interfering with different signaling pathways.

Interacting effects of graphene oxide derivatives and trace metals on freshwater brown trout (Salmo trutta L.) behaviour at different stages of development

“…39 Given the negative impact of GO on locomotor behaviour, some researchers have studied whether GO may cause neurotoxicity during the early stages of development. 9,40 Moreover, it was found that the toxicity of GO on the development, biochemistry, and behavioural parameters of zebrafish embryos and larvae is not linked to only the concentration of exposure but also to lateral size. 3 Because modifications in AChE activity have been discovered even at low concentrations of GO (0.1 and 1 mg L −1 , respectively), GO exposure alters zebrafish neurodevelopment at the very early embryonic and larval stages, which might explain the observed changes in swimming activity in larvae following GO exposure.…”

Is Graphene Shortening the Path toward Spinal Cord Regeneration?

“…110 Contrary to GO, the presence of rGO nanosheets in the zebrafish spinal cord triggered an increase in the locomotor performance directly associated with an augmentation of the local synaptic activity. 111 Interestingly, a delayed but long-term impact of rGO nanosheets on the swimming performance of zebrafish embryos was evidenced (i.e., effects detected as early as 4 h of exposure and still noticeable after 24 h). Conversely, GO flakes induced earlier (after 2 h of exposure), but not persistent (absent after 24 h of incubation), inhibitory effects.…”

Biomaterials for Regenerative Medicine in Italy: Brief State of the Art of the Principal Research Centers

“…The Neurobiology Sector of the International School for Advanced Studies (SISSA/ISAS) of Trieste is a leader in developing neurologically compatible synthetic nanomaterials for medical purposes. This institution has focused its work on GO derivatives and their impact on the nervous system for neurodegenerative disorders and synapse-based therapeutic interventions ( Figure 2 ) [ 54 ]. GO is a hydrophilic carbon material, structured as a 2D network with interesting physiochemical features such as its strength, its light weight, its high conductivity and its chemical stability.…”

“… Materials Characteristics Applications Ref. Chitosan Induce axonal growth Reduces tissue scarification Nerve grafts conduits [ 76 , 77 ] CNT Mechanical strength Thermal inertness Transparent nerve conduits Axon regeneration Spinal cord regeneration Implantable devices with suitable neural interfaces [ 62 , 63 , 64 ] Fibroin Elastic Flexible Highly resistant to stretching/compression Nerve grafts conduits Recovery of the median nerve [ 78 , 79 , 80 , 81 ] OG Mechanical strength Electrical and thermal conductivity Education of neural connections Guide neural growth and differentiation [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] PBCA Biocompatible Neural differentiation Cell culture [ 98 ] …”

“…( I ) VGLUT1-positive puncta (synaptic activity) in rGO1000 treated cultures increased significantly. Reproduced with permission [ 54 ]. * p = 0.1; *** p = 0.005.…”