Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival
Emerging scaffold structures made of carbon nanomaterials, such as graphene oxide (GO) have shown efficient bioconjugation with common biomolecules. Previous studies described that GO promotes the differentiation of neural stem cells and may be useful for neural regeneration. In this study, we exami...
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| Format: | Article |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2020.570409/full |
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| author | Noela Rodriguez-Losada Noela Rodriguez-Losada Rune Wendelbob M. Carmen Ocaña M. Carmen Ocaña Amelia Diaz Casares Roberto Guzman de Villoría Jose A. Aguirre Gomez Miguel A. Arraez Pedro Gonzalez-Alegre Pedro Gonzalez-Alegre Miguel A. Medina Miguel A. Medina Ernest Arenas Jose A. Narvaez |
| author_facet | Noela Rodriguez-Losada Noela Rodriguez-Losada Rune Wendelbob M. Carmen Ocaña M. Carmen Ocaña Amelia Diaz Casares Roberto Guzman de Villoría Jose A. Aguirre Gomez Miguel A. Arraez Pedro Gonzalez-Alegre Pedro Gonzalez-Alegre Miguel A. Medina Miguel A. Medina Ernest Arenas Jose A. Narvaez |
| author_sort | Noela Rodriguez-Losada |
| collection | DOAJ |
| description | Emerging scaffold structures made of carbon nanomaterials, such as graphene oxide (GO) have shown efficient bioconjugation with common biomolecules. Previous studies described that GO promotes the differentiation of neural stem cells and may be useful for neural regeneration. In this study, we examined the capacity of GO, full reduced (FRGO), and partially reduced (PRGO) powder and film to support survival, proliferation, differentiation, maturation, and bioenergetic function of a dopaminergic (DA) cell line derived from the mouse substantia nigra (SN4741). Our results show that the morphology of the film and the species of graphene (GO, PRGO, or FRGO) influences the behavior and function of these neurons. In general, we found better biocompatibility of the film species than that of the powder. Analysis of cell viability and cytotoxicity showed good cell survival, a lack of cell death in all GO forms and its derivatives, a decreased proliferation, and increased differentiation over time. Neuronal maturation of SN4741 in all GO forms, and its derivatives were assessed by increased protein levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), the glutamate inward rectifying potassium channel 2 (GIRK2), and of synaptic proteins, such as synaptobrevin and synaptophysin. Notably, PRGO-film increased the levels of Tuj1 and the expression of transcription factors specific for midbrain DA neurons, such as Pitx3, Lmx1a, and Lmx1b. Bioenergetics and mitochondrial dysfunction were evaluated by measuring oxygen consumption modified by distinct GO species and were different between powder and film for the same GO species. Our results indicate that PRGO-film was the best GO species at maintaining mitochondrial function compared to control. Finally, different GO forms, and particularly PRGO-film was also found to prevent the loss of DA cells and the decrease of the α-synuclein (α-syn) in a molecular environment where oxidative stress has been induced to model Parkinson's disease. In conclusion, PRGO-film is the most efficient graphene species at promoting DA differentiation and preventing DA cell loss, thus becoming a suitable scaffold to test new drugs or develop constructs for Parkinson's disease cell replacement therapy. |
| first_indexed | 2024-12-16T12:56:17Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-16T12:56:17Z |
| publishDate | 2020-12-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-005ee457450e43ae897bc5aec664086e2022-12-21T22:31:01ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-12-011410.3389/fnins.2020.570409570409Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and SurvivalNoela Rodriguez-Losada0Noela Rodriguez-Losada1Rune Wendelbob2M. Carmen Ocaña3M. Carmen Ocaña4Amelia Diaz Casares5Roberto Guzman de Villoría6Jose A. Aguirre Gomez7Miguel A. Arraez8Pedro Gonzalez-Alegre9Pedro Gonzalez-Alegre10Miguel A. Medina11Miguel A. Medina12Ernest Arenas13Jose A. Narvaez14Department Human Physiology, Faculty of Medicine, Biomedicine Research Institute of Malaga (IBIMA C07), University of Malaga, Malaga, SpainDepartment of Didactic Science Education, Faculty of Science Education, University of Malaga, Malaga, SpainABALONYX AS., Oslo, NorwayDepartment of Molecular Biology and Biochemistry, Faculty of Sciences, and IBIMA (Biomedical Research Institute of Málaga), Andalucía Tech, University of Málaga, Málaga, SpainCIBER de Enfermedades Raras (CIBERER), Málaga, SpainDepartment Human Physiology, Faculty of Medicine, Biomedicine Research Institute of Malaga (IBIMA C07), University of Malaga, Malaga, SpainLaboratory of Mechanical Engineering Applied to Design, Manufacturing and Applications of Composite Materials (LAMCOM), Department of Mechanical Engineering, University of Salamanca, Escuela Politécnica Superior de Zamora, Zamora, SpainDepartment Human Physiology, Faculty of Medicine, Biomedicine Research Institute of Malaga (IBIMA C07), University of Malaga, Malaga, SpainNeurosurgery Unit, Department Neurosurgery, Biomedicine Research Institute of Malaga (IBIMA), Hospital Regional de Malaga, Andalusian Health System (SAS), Malaga, SpainRaymond G. Perelman Center for Cellular & Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Molecular Biology and Biochemistry, Faculty of Sciences, and IBIMA (Biomedical Research Institute of Málaga), Andalucía Tech, University of Málaga, Málaga, SpainCIBER de Enfermedades Raras (CIBERER), Málaga, Spain0Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SwedenDepartment Human Physiology, Faculty of Medicine, Biomedicine Research Institute of Malaga (IBIMA C07), University of Malaga, Malaga, SpainEmerging scaffold structures made of carbon nanomaterials, such as graphene oxide (GO) have shown efficient bioconjugation with common biomolecules. Previous studies described that GO promotes the differentiation of neural stem cells and may be useful for neural regeneration. In this study, we examined the capacity of GO, full reduced (FRGO), and partially reduced (PRGO) powder and film to support survival, proliferation, differentiation, maturation, and bioenergetic function of a dopaminergic (DA) cell line derived from the mouse substantia nigra (SN4741). Our results show that the morphology of the film and the species of graphene (GO, PRGO, or FRGO) influences the behavior and function of these neurons. In general, we found better biocompatibility of the film species than that of the powder. Analysis of cell viability and cytotoxicity showed good cell survival, a lack of cell death in all GO forms and its derivatives, a decreased proliferation, and increased differentiation over time. Neuronal maturation of SN4741 in all GO forms, and its derivatives were assessed by increased protein levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), the glutamate inward rectifying potassium channel 2 (GIRK2), and of synaptic proteins, such as synaptobrevin and synaptophysin. Notably, PRGO-film increased the levels of Tuj1 and the expression of transcription factors specific for midbrain DA neurons, such as Pitx3, Lmx1a, and Lmx1b. Bioenergetics and mitochondrial dysfunction were evaluated by measuring oxygen consumption modified by distinct GO species and were different between powder and film for the same GO species. Our results indicate that PRGO-film was the best GO species at maintaining mitochondrial function compared to control. Finally, different GO forms, and particularly PRGO-film was also found to prevent the loss of DA cells and the decrease of the α-synuclein (α-syn) in a molecular environment where oxidative stress has been induced to model Parkinson's disease. In conclusion, PRGO-film is the most efficient graphene species at promoting DA differentiation and preventing DA cell loss, thus becoming a suitable scaffold to test new drugs or develop constructs for Parkinson's disease cell replacement therapy.https://www.frontiersin.org/articles/10.3389/fnins.2020.570409/fullParkinson's diseasebioenergetic dysfunctionneurodifferentiationneuronal dysfunctiongraphene oxide |
| spellingShingle | Noela Rodriguez-Losada Noela Rodriguez-Losada Rune Wendelbob M. Carmen Ocaña M. Carmen Ocaña Amelia Diaz Casares Roberto Guzman de Villoría Jose A. Aguirre Gomez Miguel A. Arraez Pedro Gonzalez-Alegre Pedro Gonzalez-Alegre Miguel A. Medina Miguel A. Medina Ernest Arenas Jose A. Narvaez Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival Frontiers in Neuroscience Parkinson's disease bioenergetic dysfunction neurodifferentiation neuronal dysfunction graphene oxide |
| title | Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival |
| title_full | Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival |
| title_fullStr | Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival |
| title_full_unstemmed | Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival |
| title_short | Graphene Oxide and Reduced Derivatives, as Powder or Film Scaffolds, Differentially Promote Dopaminergic Neuron Differentiation and Survival |
| title_sort | graphene oxide and reduced derivatives as powder or film scaffolds differentially promote dopaminergic neuron differentiation and survival |
| topic | Parkinson's disease bioenergetic dysfunction neurodifferentiation neuronal dysfunction graphene oxide |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2020.570409/full |
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