TITLE

Human Ntera2 cells as a predictive in vitro test system for developmental neurotoxicity

AUTHOR(S)
Stern, Michael; Gierse, Andrea; Tan, Saime; Bicker, Gerd
PUB. DATE
January 2014
SOURCE
Archives of Toxicology;Jan2014, Vol. 88 Issue 1, p127
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the '3Rs' (reduction, replacement, and refinement) of animal testing, alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening. The goal of this study was to establish components for a human cell-based test system to assess DNT potential of chemicals at an early stage of brain development. A human neural precursor cell line should be tested for suitability for semi-automated high-throughput DNT screening. We established assays suitable for detecting disturbances in two basic processes of brain development in 96-well scale: neuronal differentiation and migration using the human Ntera2 (NT2) cell line. We assessed the effects of four test compounds with well-established DNT potential in comparison with three compounds without specific DNT potential. We found that human NT2 cell cultures treated with the morphogen, retinoic acid, imitate neuronal differentiation, and migration in vitro. The developmental neurotoxicants methylmercury chloride, sodium arsenite, sodium valproate, and methylazoxymethanol significantly reduced the expression of the neuronal marker β-tubulin type III and decreased the migration distance in developing NT2 cells. Both endpoints, differentiation and migration, can be read out directly in a standard fluorescence plate reader, enabling high-throughput screening. We conclude that NT2 cell tests are likely to become valuable components of a human cell-based modular in vitro DNT test systems.
ACCESSION #
93436393

 

Related Articles

  • Developmental Neurotoxicity of Perfluorinated Chemicals Modeled in Vitro. Slotkin, Theodore A.; MacKillop, Emiko A.; Melnick, Ronald L.; Thayer, Kristina A.; Seidler, Frederic J. // Environmental Health Perspectives;Jun2008, Vol. 116 Issue 6, p716 

    BACKGROUND: The widespread detection of perfluoroalkyl acids and their derivatives in wildlife and humans, and their entry into the immature brain, raise increasing concern about whether these agents might be developmental neurotoxicants. OBJECTIVES: We evaluated perfluorooctane sulfonate...

  • In Vitro Techniques for the Assessment of Neurotoxicity. Harry, G. Jean; Billingsley, Melvin; Bruinink, Arend; Campbell, Iain L.; Classen, Werner; Dorman, David C.; Galli, Corrado; Ray, David; Smith, Robert A.; Tilson, Hugh A. // Environmental Health Perspectives Supplements;Feb98 Supplement 1, Vol. 106, p131 

    Presents a study on in vitro techniques for the assessment of neurotoxicity. Discussion of the strengths and limitations of techniques in their usefulness to identify hazards and the subsequent dose-response assessment; Selection and evaluation of end points used to determine potential...

  • Progress toward the development of in vitro model system for chemical-induced developmental neurotoxicity: potential applicability of stem cells. Kumar, V.; Jahan, S.; Singh, S.; Khanna, V.; Pant, A. // Archives of Toxicology;Feb2015, Vol. 89 Issue 2, p265 

    The article discusses the progress toward the development of in vitro model system for various aspects of chemical-induced developmental neurotoxicity (DNT) and potential application of stem cells. Topics discussed include the use of neuronal stem cells as a potent in vitro tool for screening...

  • Neurotoxicity Testing: A Discussion of in Vitro Alternatives. Costa, Lucio G. // Environmental Health Perspectives Supplements;Apr98 Supplement 2, Vol. 106, p505 

    Addresses the use of in vitro systems in neurotoxicology and their potential role in a general strategy for neurotoxicity testing.

  • mRNA Expression is a Relevant Tool to Identify Developmental Neurotoxicants Using an In Vitro Approach. Hogberg, Helena T.; Kinsner-Ovaskainen, Agnieszka; Coecke, Sandra; Hartung, Thomas; Bal-Price, Anna K. // Toxicological Sciences;Jan2010, Vol. 113 Issue 1, p95 

    So far, only a few industrial chemicals have been identified as developmental neurotoxicants. Because the current developmental neurotoxicity (DNT) guideline (Organisation for Economic Co-operation and Development TG 426) is based entirely on in vivo studies that are both time consuming and...

  • Workgroup Report: Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies. Coecke, Sandra; Goldberg, Alan M.; Allen, Sandra; Buzanska, Leonora; Calamandrei, Gemma; Crofton, Kevin; Hareng, Lars; Hartung, Thomas; Knaut, Holger; Honegger, Paul; Jacobs, Miriam; Lein, Pamela; Li, Abby; Mundy, William; Owen, David; Schneider, Steffen; Silbergeld, Ellen; Reum, Torsten; Trnovec, Tomas; Monnet-Tschudi, Florianne // Environmental Health Perspectives;Jun2007, Vol. 115 Issue 6, p989 

    This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19-21 April 2005. The workshop was hosted by the European Centre for the...

  • MicroRNA Profiling as Tool for In Vitro Developmental Neurotoxicity Testing: The Case of Sodium Valproate. Smirnova, Lena; Block, Katharina; Sittka, Alexandra; Oelgeschläger, Michael; Seiler, Andrea E. M.; Luch, Andreas // PLoS ONE;Jun2014, Vol. 9 Issue 6, p1 

    Studying chemical disturbances during neural differentiation of murine embryonic stem cells (mESCs) has been established as an alternative in vitro testing approach for the identification of developmental neurotoxicants. miRNAs represent a class of small non-coding RNA molecules involved in the...

  • In Silico Modeling for the Prediction of Dose and Pathway-Related Adverse Effects in Humans From In Vitro Repeated-Dose Studies. Klein, Sebastian; Maggioni, Silvia; Bucher, Joachim; Mueller, Daniel; Niklas, Jens; Shevchenko, Valery; Mauch, Klaus; Heinzle, Elmar; Noor, Fozia // Toxicological Sciences;Jan2016, Vol. 149 Issue 1, p55 

    Long-term repeated-dose toxicity is mainly assessed in animals despite poor concordance of animal data with human toxicity. Nowadays advanced human in vitro systems, eg, metabolically competent HepaRG cells, are used for toxicity screening. Extrapolation of in vitro toxicity to in vivo effects...

  • CA2+-ACTIVATED K+ CHANNELS INVOLVED IN DUODENAL DISMOTILITY INDUCED BY ETHANOL. Fagundes, D. S.; Grasa, L.; Arruebo, M. P.; Plaza, M. A.; Murillo, M. D. // Alcohol & Alcoholism;Jul/Aug2007, Vol. 42 Issue 4, p291 

    The purpose of this study was to investigate the role of K+ channels in duodenal dismotility induced by ethanol in vitro. The amplitude of spontaneous contractions was reduced by ethanol in longitudinal and circular muscle, while frequency did not change. Charybdotoxin antagonized...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics