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Imprint
Identification of electrophysiological endpoints in stem cell-based models for developmental neurotoxicity assays
Project
Project code: BfR-ZEBET-08-1328-491
Contract period: 01.05.2012
- 30.06.2013
Purpose of research: Applied research
The overall objective of the project is to establish and evaluate detection-endpoints for developmental neurotoxicity (DNT) tests in vitro, thus fulfilling 3R principles (Replacement, Reduction and Refinement) of animal testing reduction.
Neuronal NT2 and mESC cell networks were established and sustained network acitivity was analyzed in 6-well and 9-well MEAs with up to 26 electordes/chamber for increased spatial resolution. We further optimized the production of hNT neurons from NT2 cells. As endpoints, we identified the temporal and spatial structure of acitivity during development by analyzing the acute effect of Picrotoxin (GABA-A rezeptor antagonist) an mefloquine (gap-junction-blocker) on spontaneous network activity after exposure to mercury. Chronic MeHg-treatment led to a concentration dependent reduction of network formation during development, detectable as fewer recording sites with activity and reduced firing rates. We could thus show that it is possible to realize a stem-cell-based assay for functional DNT. For statistical analyses, dense spatial sampling is essential.
Section overview
Subjects
- Special animal species
Framework programme
Funding programme
Excutive institution
BfR - Centre for Documentation and Evaluation of Alternatives to Animal Experiments (BfR - ZEBET)
