By creating human serotonin-releasing brain cells in a dish, scientists have produced a very useful tool for researching an aspect of brain activity that is essential to mental well-being.
Serotonin is an important chemical that brain cells, or neurons, use to communicate with each other. It plays a key role, for example, in helping to regulate mood, appetite, and sleep.
Selective serotonin reuptake inhibitors (SSRIs) – a class of drug used to treat depression and other mental health conditions – work by inhibiting the reabsorption of serotonin by neurons so that more is available for passing messages between them.
Now, a new study published in Molecular Psychiatry reports how researchers from the Salk Institute in La Jolla, CA, and others took human skin cells and turned them into neurons that signal to one another using serotonin.
The achievement gives researchers a new tool with which to improve our understanding of serotonin’s mechanisms, which to date has come mainly from studying mice, note the authors.
Senior investigator Rusty Gage, a genetics professor at the Salk Institute, says:
“We can finally start asking questions about cells from people affected by depression and other disorders.”
For the last decade or so, it has been possible to produce various types of human cell in the lab. For example, scientists can take cells from a specific tissue, convert them into pluripotent stem cells (iPS) and then coax them to differentiate into various other types of cell, including neurons.
Researchers have also managed to produce neurons without using stem cells – by directly reprogramming skin cells. But these neurons use a different brain chemical called glutamate.
For the new study, the team used existing tools to differentiate precursor cells into neurons and then used a new technique called a “lentiviral reporter for serotonergic neurons” to separate out the serotonin-releasing neurons so they could identify which genes were uniquely active in them.
The team identified a cluster of six gene-activating proteins or transcription factors – NKX2.2, FEV, GATA2, LMX1B, ASCL1 and NGN2 – that were responsible for directing the differentiation of serotonin-releasing neurons from the skin cells.
They used the six transcription factors to reprogram human skin cells into serotonin-releasing neurons that showed many of the same properties as the ones found in the brain.
The team found that the lab-made serotonin-releasing neurons – which they dub “induced serotonergic neurons” (iSNs) – also responded to SSRIs in the same way as brain serotonin-releasing neurons.
Lead author Krishna Vadodaria, a research associate in the Gage lab, concludes:
“While these neurons may not be identical to the brain’s serotonergic neurons, the iSNs have functional properties of neurons, produce serotonin and respond to antidepressants in the dish, which will help us more accurately study serotonergic neurotransmission in neuropsychiatric disorders.”
Meanwhile, from other recently published work of great value to regenerative medicine, Medical News Today learned how a single gene drives brain development. A study published in The EMBO Journal reveals that the gene NeuroD1 is not only expressed in brain stem cells but also acts as the master regulator of the complex process through which they differentiate into different types of brain cell.