THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders
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.
|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|
|Publisher Name||Translational Psychiatry|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/29691375|