S6: Application of high content imaging
Application of high content imaging in screening approaches to detect potentially neurotoxic compounds
University of Konstanz
(Developmental) neurotoxicity generally describes any process which acts adversely on the (developing) nervous system. Many processes are involved in the functionally correct formation of the central and peripheral nervous system, and these need to be coordinated in time and space. The mature nervous system is characterized by energy consuming transport processes, large surface to volume ratios of its cells, and multiple requirements to be fulfilled maintenance of electrical activity.
A vision for future toxicology is to model all involved physiological processes in vitro and to assemble a testing battery from such models. In vitro tests have been established for the neurodevelopmental processes in out lab. They assess (i) the correct migration of neural crest cells (which form tissues such as cranial bones or the peripheral nervous system), (ii) the neurite outgrowth of dopaminergic cells, and (iii) the neurite outgrowth of sensory neurons from the peripheral nervous system.
These three tests are based on high content image quantification that allows high throughput. Essential for the usage of high throughput assays are the determination of their robustness, testing of positive and negative controls and the development of a prediction model, which translates the assay outcome into a hazard statement. Screening of a 80 compounds library with all three test was used to assess throughput under real-life conditions. Robustness and reproducibility of the methods was confirmed and the comparison of screen hits yielded information on the complementarity and convergence between the test methods.