BBB project – Effects of Endocrine Disrupting Chemicals on Development and Functioning of the Blood Brain Barrier
In this project, we test the hypothesis that exposure to endocrine disrupting chemicals (EDCs) affects development and proper functioning of the blood-brain barrier (BBB). Dysfunction of the BBB has been associated with neurodevelopmental disorders. As a first step, we have identified EDCs associated with impaired neurodevelopment (in collaboration with Karlstad University and the SELMA pregnancy cohort). We are now studying the effects of selected chemicals (Bisphenol A, Bisphenol S and Bisphenol F) in a cell-based model of the human BBB. In this model, induced pluripotent stem cells (iPSCs) are differentiated into brain microvascular endothelial cells grown on Transwell® polyester membrane cell culture inserts. These endothelial cells express relevant markers of the BBB and show good transepithelial resistance (TEER), indicating that they have formed a functional barrier. To test the effects of EDCs on the forming and functioning of the BBB, the cells are differentiated in the presence or absence of EDCs in order to mimic the foetal condition where EDCs are present during the whole barrier formation. The chemical concentrations have been selected to be of relevance in the human population, based on the concentrations measured in the pregnant women.
The project will lead to important insights on the effects of EDCs on the human BBB, and thus contribute to a better understanding of how EDCs affect neurodevelopment.
Project funding: Formas project grant
Responsible researchers: Dr. Elin Engdahl, Prof. Joëlle Rüegg .
Main collaborators: Assoc. Prof. Anna Herland, KTH; Prof. Carl-Gustaf Bornehag, Karlstad University