title: Human iPSC neurons display activity-dependent neurotransmitter secretion: aberrant catecholamine levels in schizophrenia neurons.
abstract: This study investigated human-induced pluripotent stem cell (hiPSC) -derived neurons for their ability to secrete neurotransmitters in an activity-dependent manner, the fundamental property required for chemical neurotransmission. Cultured hiPSC neurons showed KCl stimulation of activity-dependent secretion of catecholamines--dopamine (DA), norepinephrine (NE), and epinephrine (Epi)--and the peptide neurotransmitters dynorphin and enkephlain. hiPSC neurons express the biosynthetic enzymes for catecholamines and neuropeptides. Because altered neurotransmission contributes to schizophrenia (SZ), we compared SZ to control cultures of hiPSC neurons and found that SZ cases showed elevated levels of secreted DA, NE, and Epi. Consistent with increased catecholamines, the SZ neuronal cultures showed a higher percentage of tyrosine hydroxylase (TH)-positive neurons, the first enzymatic step for catecholamine biosynthesis. These findings show that hiPSC neurons possess the fundamental property of activity-dependent neurotransmitter secretion and can be advantageously utilized to examine regulation of neurotransmitter release related to brain disorders.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA; Department of Neurosciences, Department of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: vhook@ucsd.edu.
authors.forename: Vivian
authors.initials: V
authors.lastname: Hook
authors.affiliation: The Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Brennand
authors.affiliation: The Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Yongsung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Toneff
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Lydiane
authors.initials: L
authors.lastname: Funkelstein
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ziegler
authors.affiliation: The Salk Institute, La Jolla, CA 92037, USA.
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D004399:Dynorphins / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D005089:Exocytosis; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D007231:Infant, Newborn; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D004745:Enkephalins; D004399:Dynorphins