Universität zu Köln

Schmidt, Bela Z., Lehmann, Martin, Gutbier, Simon, Nembo, Erastus, Noel, Sabrina, Smirnova, Lena, Forsby, Anna ORCID: 0000-0001-6298-201X, Hescheler, Juergen, Avci, Hasan X., Hartung, Thomas, Leist, Marcel ORCID: 0000-0002-3778-8693, Kobolak, Julianna ORCID: 0000-0002-0986-9517 and Dinnyes, Andras ORCID: 0000-0003-3791-2583 (2017). In vitro acute and developmental neurotoxicity screening: an overview of cellular platforms and high-throughput technical possibilities. Arch. Toxicol., 91 (1). S. 1 - 34. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1432-0738

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schmidt, Bela Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutbier, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Nembo, Erastus UNSPECIFIED UNSPECIFIED UNSPECIFIED Noel, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Smirnova, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Forsby, Anna UNSPECIFIED orcid.org/0000-0001-6298-201X UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Avci, Hasan X. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartung, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Leist, Marcel UNSPECIFIED orcid.org/0000-0002-3778-8693 UNSPECIFIED Kobolak, Julianna UNSPECIFIED orcid.org/0000-0002-0986-9517 UNSPECIFIED Dinnyes, Andras UNSPECIFIED orcid.org/0000-0003-3791-2583 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-242968
DOI:	10.1007/s00204-016-1805-9
Journal or Publication Title:	Arch. Toxicol.
Volume:	91
Number:	1
Page Range:	S. 1 - 34
Date:	2017
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1432-0738
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EMBRYONIC STEM-CELLS; BLOOD-BRAIN-BARRIER; HISTONE DEACETYLASE INHIBITORS; INTEGRATED TESTING STRATEGIES; HUMAN DOPAMINERGIC-NEURONS; NECROSIS-FACTOR RECEPTOR; NEURAL CREST MIGRATION; GLIAL-CELLS; SYSTEMIC TOXICITY; OXIDATIVE STRESS Multiple languages Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24296