A group of researchers at the University of Wisconsin have successfully created serotonin-producing neurons in the lab. This breakthrough could help researchers study illnesses that involve serotonin, such as depression and schizophrenia, as well as form new treatments and medications for these ailments. The study was published in the scientific journal Nature Biotechnology.
What is serotonin?
Serotonin is a neurotransmitter, or a chemical that neurons use to communicate with each other. Serotonin neurons are located in the raphe nucleus, a brain region located within the brainstem. These neurons communicate with the rest of the brain and are responsible for regulating numerous activities including mood, sleep and appetite.
Serotonin imbalances have been linked to a wide variety of psychiatric disorders including depression, generalized anxiety disorder, obsessive compulsive disorder, bipolar disorder and schizophrenia. Serotonin levels have also been associated with Huntington’s and Alzheimer’s diseases.
So far, researchers have managed to create serotonin neurons in the lab, but these older methods resulted in very few neurons, making the cells difficult to study.
“Previously, labs were producing a few percent of serotonin neurons from pluripotent stem cells, and that made it very difficult to study their cells,” explained Jianfeng Lu, Ph.D., the lead author of the current study. “If you detect 10 neurons, and only two are serotonin neurons, it’s impossible to detect serotonin release; that was the stone in the road.”
The current study
To create a large quantity of serotonin-producing neurons, the researchers used pluripotent stem cells, or undifferentiated cells that have the potential to transform into another cell type. The researchers exposed these stem cells to WNT — a molecule that controls the development and placement of serotonin neurons — and to sonic hedgehog — a molecule that controls the development of embryonic cells (despite its silly name).
Su-Chun Zhang, M.D., Ph.D., the senior researcher on the study, explained:
“Here, we had to instruct the stem cells to develop into one specific fate, using a custom-designed sequence of molecules at exact concentrations. That’s especially difficult if you consider that the conditions needed to make serotonin neurons are scarce, existing in one small location in the brain during development.”
The new cells that the researchers created resembled serotonin neurons in multiple ways: 1) they expressed tryptophan hydroxylase, an enzyme responsible for serotonin synthesis, 2) they had electrical characteristics that were identical to those found in serotonin neurons, and 3) they released serotonin when given tramadol or escitalopram, two drugs known to increase serotonin levels in the brain.
“We think these can help develop new, more effective drugs, especially related to the higher neural functions that are so difficult to model in mice and rats,” explained Zhang. “Particularly because they are from humans, these cells may lead to benefits for patients with depression, bipolar disorder or anxiety. These are some of the most troublesome psychiatric conditions, and we really don’t have great drugs for them now.”
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About the author
Courtney Lopresti, M.S., is a senior staff writer for the Sovereign Health Group where she uses her scientific background to write online blogs and articles for a general audience. At the University of Pittsburgh, where she earned her Master’s in neuroscience, she used functional neuroimaging to study how the human cerebellum contributes to language processing. In her spare time, she writes fiction, reads Oliver Sacks and spends time with her two cats and bird. Courtney is currently located in Minneapolis. For more information and other inquiries about this article, contact the author at firstname.lastname@example.org.