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Stem Cell Reports. 2014 Oct 14;3(4):531-8. doi: 10.1016/j.stemcr.2014.08.001. Epub 2014 Sep 11.

Human iPSC neurons display activity-dependent neurotransmitter secretion: aberrant catecholamine levels in schizophrenia neurons.

Author information

1
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.
2
The Salk Institute, La Jolla, CA 92037, USA.
3
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
4
Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.

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.

PMID:
25358781
PMCID:
PMC4223699
DOI:
10.1016/j.stemcr.2014.08.001
[Indexed for MEDLINE]
Free PMC Article

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