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Updated: Sep 21, 2025
Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
Published on: April 12, 2015
Human cerebral spheroids undergo 4-aminopyridine-induced, activity associated changes in cellular composition and
Thomas Parmentier1,2, Fiona M K James3, Elizabeth Hewitson1
1Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
Abstract:
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 4-aminopyridine (4AP) on neuronal activity and associated neurogenesis. Our studies demonstrate that 4AP increases neuronal activity in 3-month-old cerebral spheroids while increasing numbers of new neurons and decreasing 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 several aspects of activity-induced neurogenesis.
