Rationale for the research area
Prediction of neurotoxic effects in adult and developing brain is an important issue. Toxicants, such as drugs or environmental pollutants, can induce early neural tube defects, can interfere with neuronal and glial differentiation, or can lead to neurodegeneration. There is therefore a need to test for neurotoxicity at different stages of brain development after acute exposure and after repeated exposure with low doses. This project aims at developing and validating several in vitro models with cells of human origin in order to cover these different aspects of neurotoxicity testing. In addition, the use of a well-characterized 3D model, the aggregating rat brain cell cultures, will allow the study of neurotoxicant-induced neuroinflammation and its involvement in neurodegeneration.
To develop a test battery using genomic, proteomic, electrophysiological and morphological endpoints in order to assess adverse effects of toxicants at different stages of brain development. To identify functional pathways related to toxicity mechanisms as well as potential biomarkers of neurotoxicity.
The obtained data will be used for the development of Adverse Outcome Pathways (AOPs), that will be useful for risk assessment and finally for regulatory purposes.