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The Neurosphere Assay as an In Vitro Method for Developmental Neurotoxicity (DNT) Evaluation

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Cell Culture Techniques

Part of the book series: Neuromethods ((NM,volume 145))

Abstract

The human developing central nervous system is more vulnerable to the adverse effects of chemical agents than the adult brain. At present, due to the lack of available data on human neurodevelopmental toxicants, there is an urgent need for testing and subsequently regulating chemicals for their potential to interfere with nervous system development. Alternative testing strategies might fill that gap as they allow fast and resource-efficient compound screenings for a variety of neurodevelopmental endpoints. Nervous system development is complex calling for a battery of tests that cover early and late developmental stages and a variety of neurodevelopmental processes. One of such assays is the “neurosphere assay,” an in vitro 3D model for developmental neurotoxicity (DNT) evaluation based on human neural progenitor cells. With this assay, one can identify compounds that disturb basic neurodevelopmental processes, such as NPC proliferation, migration, neuronal- and oligodendrocyte differentiation, as well as thyroid hormone (TH)-dependent oligodendrocyte maturation. By including viability and cytotoxicity assays into the workflow, the assays allow the distinction of specific DNT from general cytotoxicity. This chapter explains how the different test methods of the “neurosphere assay,” i.e., NPC1–6, are performed and how some of them can be multiplexed in a time- and cost-efficient manner.

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Author information

Author notes

  1. Laura Nimtz, Jördis Klose, and Stefan Masjosthusmann are contributed equally to this manuscript.

Authors and Affiliations

  1. IUF – Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany

    Laura Nimtz, Jördis Klose, Stefan Masjosthusmann & Ellen Fritsche

  2. INSA·UB and Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain

    Marta Barenys

  3. Heinrich-Heine-University, Duesseldorf, Germany

    Ellen Fritsche

Authors
  1. Laura Nimtz
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  2. Jördis Klose
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  3. Stefan Masjosthusmann
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  4. Marta Barenys
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  5. Ellen Fritsche
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Corresponding author

Correspondence to Ellen Fritsche .

Editor information

Editors and Affiliations

  1. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA

    Michael Aschner

  2. Department of Environment/STE 100, University of Washington, Seattle, WA, USA

    Lucio Costa

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Nimtz, L., Klose, J., Masjosthusmann, S., Barenys, M., Fritsche, E. (2019). The Neurosphere Assay as an In Vitro Method for Developmental Neurotoxicity (DNT) Evaluation. In: Aschner, M., Costa, L. (eds) Cell Culture Techniques. Neuromethods, vol 145. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9228-7_8

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  • DOI: https://doi.org/10.1007/978-1-4939-9228-7_8

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9227-0

  • Online ISBN: 978-1-4939-9228-7

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