Promotion of Neuronal Guidance Growth by Aminated Graphene Oxide via Netrin-1/Deleted in Colorectal Cancer Signaling

Abstract

Promotion of neurite outgrowth and synapse formation is a key step for nervous tissue regeneration. It is important for finding a new biomaterial to guide neuron growth to target neurons. Aminated graphene oxide (NH2-GO) displays electrical properties and dispersibility, which may change the surface charge of neurons and further activate neuronal excitement. However, the molecular guidance mechanism of NH2-GO on neurite outgrowth is seldom reported. In this study, we compared the role of NH2-GO on the spinal cord neurons and cortical neurons. Results indicated that the proper concentrations were at 2 and 4 μg/mL as determined by the CCK-8 assay. Notably, NH2-GO (2 and 4 μg/mL) improved the dispersibility and strengthened the effect of the composite material. In addition, it enables biocompatibility and efficient guidance of growth performance, which is not neurotoxic for neuronal outgrowth under these two concentrations. More interestingly, NH2-GO at 2 μg/mL induced both marked neurite elongation and increased branches in cortical neurons, but there is no significant change of neurite length and branches in spinal cord neurons. Further, the fluorescence intensity and mRNA level of Netrin-1 and DCC (Deleted in Colorectal Cancer) were both enhanced by NH2-GO at 2 μg/mL. Moreover, the function of Netrin-1 and DCC were activated more significantly by NH2-GO at 2 μg/mL in cortical neurons than that of spinal cord neurons. When RhoA was inhibited by the C3 exoenzyme, phosphorylated Rac1 and Cdc42 expression decreased significantly. Thus, NH2-GO at 2 μg/mL could influence Netrin-1/DCC signaling and the downstream RhoGTPase pathway, which may be preferred to guide the neurite growth in cortical neurons. It will provide a promising approach for the development of novel therapeutic methods of nerve regeneration.

Promising Graphene-Based Nanomaterials and Their Biomedical Applications and Potential Risks: A Comprehensive Review

“…Notably, sodium channel electricity and action potentials are generated in the absence of any nerve inducer; simultaneously, prominent axonal arrangements can be induced . The surface charge of GO greatly influences the processes and branches of neuronal axons …”

“…136 The surface charge of GO greatly influences the processes and branches of neuronal axons. 137 Moreover, numerous reports indicate that GBN materials characterized by multipore size and high specific surface area ratio are ideal for skin tissue engineering. Modifications using polyurethane, PCL, PLA, glycolic acid, PLGA, and poly(vinyl alcohol) ensure good hydrophilicity and surface ductility, which potentially provoke the adhesion and proliferation of fibroblasts on the bracket.…”

Mechanical Stretch Promotes Neurite Outgrowth of Primary Cultured Dorsal Root Ganglion Neurons via Suppression of Semaphorin 3A-Neuropilin-1/Plexin-A1 Signaling

“…All cells were observed and photographed in BF by an inverted fluorescence microscope (IX71, Olympus Inc., Japan) after the application of varying mechanical stretches. The axonal deflection angle, axonal length, and cell body size were calculated by DP2-BSW software (Olympus, Japan) and ImageJ, as described previously …”

“…The axonal deflection angle, axonal length, and cell body size were calculated by DP2-BSW software (Olympus, Japan) and ImageJ, as described previously. 38 The axon deflection angle was measured from the vertical direction (stretching direction as 0°). If the axon deflection angle is closer to 0°, the neurons grow more along the mechanical stretching direction.…”

Non-covalent attachment of BODIPY-caged amines to graphene and their localized photocleavage

“…An amine group was selected as the target functionality due to its key role in a variety of biological compounds and its potential for targeted binding. 8,17,22…”