Establishing a novel in vitro-model for inflammation induced depression based on human iPSC-derived co-culture of serotonergic neurons, microglia, and mast cells

• Applicant: Dr. Bettina Bohl
• Subject Area: Biological Psychiatry ; Molecular and Cellular Neurology and Neuropathology
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505781658

The aim of this project is to establish a human cell culture model of depression and neuroinflammation by co-cultivation of iPSC-derived serotonergic neurons, microglia and mast cells. The first goal is the development of robust differentiation protocols in three independent human iPSC lines which will be the basis to generate reproducible and reliable results. In the following, the effect of neuroinflammatory processes on serotonergic neurons will be assessed. Controlled treatment of isolated serotonergic neurons with pro-inflammatory mediators as well as the effect of external inflammatory stimuli applied to co-cultures will be analysed. In close collaboration with the bioengineers of the Hashemi lab, a high-throughput in vitro-platform based on the multielectrode array (MEA) technology shall be developed. This will be utilized to detect extracellular serotonin and histamine levels released from neurons and immune cells, respectively, by Fast Scan Cyclic Voltammery (FSCV). The established cell culture conditions will be adapted for parallel assessment of different cell lines and/or different treatments in a well-plate format. Finally, agents targeting serotonin and histamine release, respectively, will be characterized for their potential to alter serotonin/histamine ratios in the culture medium and potentially restore a physiological ratio of the biomarkers. As a prospect, this platform can be adapted for patient-derived iPSCs and function as a tool for personalized diagnostic and treatment of depression.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professorin Dr. Parastoo Hashemi