In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities

Béla Z. Schmidt, Martin Lehmann, Simon Gutbier, Erastus Nembo, Sabrina Noel, Lena Smirnova, Anna Forsby, Jürgen Hescheler, Hasan X. Avci, Thomas Hartung, Marcel Leist, Julianna Kobolák, A. Dinnyés

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Neurotoxicity and developmental neurotoxicity are important issues of chemical hazard assessment. Since the interpretation of animal data and their extrapolation to man is challenging, and the amount of substances with information gaps exceeds present animal testing capacities, there is a big demand for in vitro tests to provide initial information and to prioritize for further evaluation. During the last decade, many in vitro tests emerged. These are based on animal cells, human tumour cell lines, primary cells, immortalized cell lines, embryonic stem cells, or induced pluripotent stem cells. They differ in their read-outs and range from simple viability assays to complex functional endpoints such as neural crest cell migration. Monitoring of toxicological effects on differentiation often requires multiomics approaches, while the acute disturbance of neuronal functions may be analysed by assessing electrophysiological features. Extrapolation from in vitro data to humans requires a deep understanding of the test system biology, of the endpoints used, and of the applicability domains of the tests. Moreover, it is important that these be combined in the right way to assess toxicity. Therefore, knowledge on the advantages and disadvantages of all cellular platforms, endpoints, and analytical methods is essential when establishing in vitro test systems for different aspects of neurotoxicity. The elements of a test, and their evaluation, are discussed here in the context of comprehensive prediction of potential hazardous effects of a compound. We summarize the main cellular characteristics underlying neurotoxicity, present an overview of cellular platforms and read-out combinations assessing distinct parts of acute and developmental neurotoxicology, and highlight especially the use of stem cell-based test systems to close gaps in the available battery of tests.

Original languageEnglish
Pages (from-to)1-33
Number of pages33
JournalArchives of Toxicology
DOIs
Publication statusAccepted/In press - Aug 4 2016

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Stem cells
Screening
Animals
Cells
Throughput
Extrapolation
Chemical hazards
Induced Pluripotent Stem Cells
Systems Biology
Toxicity
Neural Crest
Tumors
Assays
Embryonic Stem Cells
Tumor Cell Line
Toxicology
Cell Movement
Stem Cells
Monitoring
Testing

Keywords

  • Assay development
  • Cell death
  • Developmental neurotoxicity
  • Electrophysiology
  • High-throughput screening
  • In vitro testing
  • Neurodevelopment
  • Neurotoxicity
  • Stem cells

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

In vitro acute and developmental neurotoxicity screening : an overview of cellular platforms and high-throughput technical possibilities. / Schmidt, Béla Z.; Lehmann, Martin; Gutbier, Simon; Nembo, Erastus; Noel, Sabrina; Smirnova, Lena; Forsby, Anna; Hescheler, Jürgen; Avci, Hasan X.; Hartung, Thomas; Leist, Marcel; Kobolák, Julianna; Dinnyés, A.

In: Archives of Toxicology, 04.08.2016, p. 1-33.

Research output: Contribution to journalArticle

Schmidt, BZ, Lehmann, M, Gutbier, S, Nembo, E, Noel, S, Smirnova, L, Forsby, A, Hescheler, J, Avci, HX, Hartung, T, Leist, M, Kobolák, J & Dinnyés, A 2016, 'In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities', Archives of Toxicology, pp. 1-33. https://doi.org/10.1007/s00204-016-1805-9
Schmidt, Béla Z. ; Lehmann, Martin ; Gutbier, Simon ; Nembo, Erastus ; Noel, Sabrina ; Smirnova, Lena ; Forsby, Anna ; Hescheler, Jürgen ; Avci, Hasan X. ; Hartung, Thomas ; Leist, Marcel ; Kobolák, Julianna ; Dinnyés, A. / In vitro acute and developmental neurotoxicity screening : an overview of cellular platforms and high-throughput technical possibilities. In: Archives of Toxicology. 2016 ; pp. 1-33.
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