Carboxylated graphene oxide promoted axonal guidance growth by activating Netrin‐1/deleted in colorectal cancer signaling in rat primary cultured cortical neurons

Abstract

Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the neuronal guidance growth are still not reported. In the present study, graphene oxide (GO) and carboxylated graphene oxide (GO-COOH) were used to investigate the potential effects on axonal guidance growth in the primary cultured cortical neurons. In addition, we characterized the structure and chemical composition of synthesized GO and GO-COOH using Fourier transform infrared spectrophotometer and scanning electron microscope assays and Raman analysis. GO is not neurotoxic and not conductive in a soluble form. However, GO-COOH has higher solubility and conductivity. Cell viability was assessed using CCK-8 assays and fluorescein diacetate after GO and GO-COOH treatment (0, 1, 2, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 50, and 100 µg/mL). There are significant increases of cell viability and axonal growth after GO (2 and 4 μg/mL) and GO-COOH treatment (2 and 4 μg/mL). We further investigated the molecular mechanism of axonal guidance growth after GO and GO-COOH (2 and 4 μg/mL) application. Additionally, GO and GO-COOH up-regulated expression of Netrin-1 and its receptor, deleted in colorectal cancer by immunofluorescence assays and western blots assay. Our study demonstrated that GO-COOH activated Cdc42 and Rac1 and dramatically decreased RhoA. Thus, GO-COOH (2 µg/mL) is much better to be nanocarriers than GO for axonal guidance and growth in this study. GO-COOH may be used to facilitate guidance for regenerating neurons in the future. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1500-1510, 2018.

Aligned graphene/silk fibroin conductive fibrous scaffolds for guiding neurite outgrowth in rat spinal cord neurons

“…Netrin‐1 takes a different effect of attraction or exclusion on axons by interacting with its specific receptors. The previous study demonstrated that the Netrin‐1/DCC signaling pathway played a vital role in axonal guidance and growth of primary cultured cortical neurons (Liu et al, 2015; Liu, Jia, et al, 2018), so here we hypothesized that aligned G/SF scaffolds could mediate Netrin‐1/DCC signaling pathway to promote axonal guidance growth on spinal cord neurons. The results showed that aligned scaffolds had a significant increase in neurite connection compared with the nonaligned SF group with the raised Netrin‐1 expression.…”

“…In order to observe the neurite outgrowth on different G/SF scaffolds, all cells were subjected to immunostaining test according to our previous methods (Liu et al, 2018). β‐Tubulin III was stained to detect neurite cytoskeleton, photos were captured by fluorescence microscope (IX71, Olympus Inc., Japan).…”

“…Cells growing in the different G/SF scaffolds were lysed to collect protein and then detected by western blots assay according to our previous study (Liu, Jia, et al, 2018). Netrin‐1 is one of the key axonal guidance cues, which was activated to direct the neuronal growth way to growth cone.…”

Insights into the Role of Graphene/Graphene‐hybrid Nanocomposites in Antiviral Therapy

“…Consequently, the hydrophilic GO could be well dispersed in an aqueous environment. The aqueous dispersibility facilitates the production of the desired shape of graphene and graphene derivatives such as sheets and films [38,109]. Meanwhile, the large surface area allows the conjunction of targeted molecules, thus making GO as a potential drug carrier [48].…”

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

“…Our recent study indicated that graphene can influence growth of neurons by triggering the Netrin-1/DCC (Deleted in Colorectal Cancer) pathway. 25 However, graphene as a different type can cause neurotoxicity in neuronal growth to a certain degree. The role of NH 2 -GO in guiding the neuronal growth needs to be investigated.…”