RT Journal Article SR Electronic T1 Human Cerebral Spheroids Undergo Activity Dependent Changes In Cellular Composition And Microrna Expression JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.02.04.478858 DO 10.1101/2022.02.04.478858 A1 Thomas Parmentier A1 Fiona James A1 Elizabeth Hewitson A1 Craig Bailey A1 Nicholas Werry A1 Steve D. Sheridan A1 Roy H. Perlis A1 Melissa Perreault A1 Luis Gaitero A1 Jasmin Lalonde A1 Jonathan LaMarre YR 2022 UL http://biorxiv.org/content/early/2022/02/06/2022.02.04.478858.abstract AB Activity-induced neurogenesis has been extensively studied in rodents but the lack of ante mortem accessibility to human brain at the cellular and molecular levels limits studies of the process in humans. Using cerebral spheroids derived from human induced pluripotent stem cells (iPSCs), we investigated the effects of increased neuronal activity on neurogenesis. Our studies demonstrate that increasing neuronal activity with 4-aminopyridine in 3-month-old cerebral spheroids is associated with increases in the numbers of new neurons and decreases in the population of new glial cells. We also observed a significant decrease in the expression of miR-135a, which has previously been shown to be decreased in exercise-induced neurogenesis. Predicted targets of miR-135a include key participants in the SMAD2/3 and BDNF pathways. Together, our results suggest that iPSC-derived cerebral spheroids are an attractive model to study some aspects of activity-induced neurogenesis.Competing Interest StatementThe authors have declared no competing interest.