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THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders

Abstract

There is a strong association between cannabis use and schizophrenia but the underlying cellular links are poorly understood. Neurons derived from human-induced pluripotent stem cells (hiPSCs) offer a platform for investigating both baseline and dynamic changes in human neural cells. Here, we exposed neurons derived from hiPSCs to Delta(9)-tetrahydrocannabinol (THC), and identified diagnosis-specific differences not detectable in vehicle-controls. RNA transcriptomic analyses revealed that THC administration, either by acute or chronic exposure, dampened the neuronal transcriptional response following potassium chloride (KCl)-induced neuronal depolarization. THC-treated neurons displayed significant synaptic, mitochondrial, and glutamate signaling alterations that may underlie their failure to activate appropriately; this blunted response resembles effects previously observed in schizophrenia hiPSC- derived neurons. Furthermore, we show a significant alteration in THC-related genes associated with autism and intellectual disability, suggesting shared molecular pathways perturbed in neuropsychiatric disorders that are exacerbated by THC.

Type Journal
ISBN 2158-3188 (Electronic) 2158-3188 (Linking)
Authors Guennewig, B.; Bitar, M.; Obiorah, I.; Hanks, J.; O'Brien, E. A.; Kaczorowski, D. C.; Hurd, Y. L.; Roussos, P.; Brennand, K. J.; Barry, G.
Responsible Garvan Author (missing name)
Publisher Name Translational Psychiatry
Published Date 2018-04-25
Published Volume 8
Published Issue 1
Published Pages 89
Status Published in-print
DOI 10.1038/s41398-018-0137-3
URL link to publisher's version http://www.ncbi.nlm.nih.gov/pubmed/29691375