Generated Serotonin Could Lead To New Depression Treatments

“Our work demonstrates that the precious serotonin neurons hidden deep inside the human brain can now be created in a petri dish,” said Feng, lead author.

Induced serotonin neurons would be extremely beneficial since they can be generated from individual patients suffering from the illness involving the neurotransmitter.

“These patient-specific serotonin neurons will be very useful to the discovery of new drugs for diseases ranging from depression and anxiety to obsessive-compulsive disorder and many others.”

“They will not only allow researchers to study why certain individuals develop a disease but also what can be done to treat it,” said Feng, who also holds an appointment as research scientist at the Buffalo VA Medical Center. 

This research demonstrates the first direct conversion of human fibroblasts into serotonergic neurons. The induced serotonergic neurons behave like serotonin neurons in the human brain. 

Feng and his team found they could produce induced serotonergic neurons from fibroblasts by introducing four genes that control the development of serotonin neurons. "These genes change how the human genome, which is like a computer hard drive, is read, so that the cell switches from a lung cell to a serotonin neuron," said Feng.

“We know the cells were converted to serotonergic neurons because they express proteins that are only found in neurons that produce serotonin,” Feng explained. “They are electrophysiologically active and demonstrate both the controlled release and selective uptake of serotonin,” he said.

Though the paper focuses on converting lung fibroblasts to serotonin neurons, Feng's group has been working on generating serotonin neurons from human skin cells, which would be a less invasive and easier process. 

The research team’s findings are applicable to generating other previously inaccessible human cell types, providing a boon to medical research and drug discovery, said Feng. 

“This research shows that it is possible to convert one type of cell into other types that have been difficult to access, such as neurons or heart cells,” he said.

Once researchers find out the combination of transcription factors that is necessary they can regenerate cells and eventually tissues that will mimic the real cells and tissues. 

The study, “Direct Conversion of Human Fibroblasts to Induced Serotonergic Neurons,” was published in Molecular Psychiatry.  

Feng’s UB co-authors, from the Department of Physiology and Biophysics, are:

• Zhen Yan, PhD, professor
• Ping Zhong, PhD, research assistant professor
• Houbo Jiang, PhD, research assistant professor

The study is also co-authored by Zhimin Xu and Shengdi Chen, both of Ruijin Hospital and Shanghai Jiao Tong University School of Medicine.

Funding was provided by:

• National Key Basic Research Program of China
• National Natural Science Foundation of China
• U.S. Department of Veterans Affairs
• NYSTEM
• National Institutes of Health