Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons

de Leeuw, Victoria C.; van Oostrom, Conny T. M.; Zwart, Edwin P.; Heusinkveld, Harm J.; Hessel, Ellen V. S.

doi:10.3390/ijms24043608

Open AccessArticle

Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons

by

Victoria C. de Leeuw

^*,†

,

Conny T. M. van Oostrom

^†,

Edwin P. Zwart

,

Harm J. Heusinkveld

and

Ellen V. S. Hessel

Centre for Health Protection (GZB), National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2023, 24(4), 3608; https://doi.org/10.3390/ijms24043608

Submission received: 21 December 2022 / Revised: 3 February 2023 / Accepted: 7 February 2023 / Published: 10 February 2023

(This article belongs to the Special Issue Pharmacology of Neurodegenerative Diseases)

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Abstract

Dopamine is present in a subgroup of neurons that are vital for normal brain functioning. Disruption of the dopaminergic system, e.g., by chemical compounds, contributes to the development of Parkinson’s disease and potentially some neurodevelopmental disorders. Current test guidelines for chemical safety assessment do not include specific endpoints for dopamine disruption. Therefore, there is a need for the human-relevant assessment of (developmental) neurotoxicity related to dopamine disruption. The aim of this study was to determine the biological domain related to dopaminergic neurons of a human stem cell-based in vitro test, the human neural progenitor test (hNPT). Neural progenitor cells were differentiated in a neuron-astrocyte co-culture for 70 days, and dopamine-related gene and protein expression was investigated. Expression of genes specific for dopaminergic differentiation and functioning, such as LMX1B, NURR1, TH, SLC6A3, and KCNJ6, were increasing by day 14. From day 42, a network of neurons expressing the catecholamine marker TH and the dopaminergic markers VMAT2 and DAT was present. These results confirm stable gene and protein expression of dopaminergic markers in hNPT. Further characterization and chemical testing are needed to investigate if the model might be relevant in a testing strategy to test the neurotoxicity of the dopaminergic system.

Keywords: neurotoxicity; neurodegeneration; human embryonic stem cells; dopaminergic neurons; in vitro

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MDPI and ACS Style

de Leeuw, V.C.; van Oostrom, C.T.M.; Zwart, E.P.; Heusinkveld, H.J.; Hessel, E.V.S. Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons. Int. J. Mol. Sci. 2023, 24, 3608. https://doi.org/10.3390/ijms24043608

AMA Style

de Leeuw VC, van Oostrom CTM, Zwart EP, Heusinkveld HJ, Hessel EVS. Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons. International Journal of Molecular Sciences. 2023; 24(4):3608. https://doi.org/10.3390/ijms24043608

Chicago/Turabian Style

de Leeuw, Victoria C., Conny T. M. van Oostrom, Edwin P. Zwart, Harm J. Heusinkveld, and Ellen V. S. Hessel. 2023. "Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons" International Journal of Molecular Sciences 24, no. 4: 3608. https://doi.org/10.3390/ijms24043608

APA Style

de Leeuw, V. C., van Oostrom, C. T. M., Zwart, E. P., Heusinkveld, H. J., & Hessel, E. V. S. (2023). Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons. International Journal of Molecular Sciences, 24(4), 3608. https://doi.org/10.3390/ijms24043608

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Prolonged Differentiation of Neuron-Astrocyte Co-Cultures Results in Emergence of Dopaminergic Neurons

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