Direct effects of prolonged TNF-α and IL-6 exposure on neural activity in human iPSC-derived neuron-astrocyte co-cultures

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 tumor necrosis factor alpha (TNF). Transcriptomic analysis was conducted at day 7 of exposure to evaluate gene expression changes that could have contributed to how neurons communicated following TNF exposure. 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 TNF (25 pg/mL, 10 ng/mL, and 100 ng/mL) for 7 days, after which RNA was isolated and sequnced to determine TNF exposure induced transcriptional changes.