Biphasic response of human iPSC-derived neural network activity following exposure to a sarin-surrogate nerve agent
In a concentration-response study, we have employed a human-relevant brain microphysiological system (bMPS), containing human-iPSC derived glutamatergic and GABAergic neurons co-cultured with primary human astrocytes, to monitor and detect the changes in the electrical activity of engineered human iPSC-derived neural networks to increasing concentrations of the sarin surrogate, 4-nitrophenylisopropyl methylphosphonate (NIMP). Transcriptomic analysis was conducted at 6-days post exposure to evaluate gene expression changes that could have contributed to how neurons communicated following NIMP exposure. Overall design: human iPSC-derived glutamatergic and GABAergic neurons co-cultured with primary human astrocytes were co-cultured on a 6-well multi-electrode array. Co-cultures were allowed to mature for up to 25 DIV before exposed to one of 3 concentrations  of NIMP (0,  4, and 100 micromolar) for 24 hours. After 24 hours NIMP was removed, and co-cultures were maintained for up to 6-days post-exposure. At 6-days post-exposure, RNA was isolated and sequnced to determine NIMP exposure induced transcriptional changes.