Serotonin in psychiatry: in vitro disease modeling using patient-derived neurons

Abstract

Several lines of evidence implicate serotonin in the etiology of multiple psychiatric disorders, especially mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD). Much of our current understanding of biological mechanisms underlying serotonergic alterations in mood disorders comes from animal studies. Innovation in induced pluripotent stem cell and transdifferentiation technologies for deriving neurons from adult humans has enabled the study of disease-relevant cellular phenotypes in vitro. In this context, human serotonergic neurons can now be generated using three recently published methodologies. In this mini-review, we broadly discuss evidence linking altered serotonergic neurotransmission in MDD and BD and focus on recently published methods for generating human serotonergic neurons in vitro.

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Figure 1.

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Acknowledgements

This work has been supported by the Swiss National Science Foundation (PD outgoing fellowship, K.C.V.), the Lynn and Edward Streim fellowship (K.C.V.), Takeda-Sanford Innovation Allianc e Grant, the Paul G. Allen Family Foundation, Bob and Mary Jane Engman, The JPB Foundation, The Leona M. and Harry B. Helmsley Charitable Trust grant #2012-PG-MED002, Annette C. Merle-Smith and NIMH grant U19MH106434. The authors would like to thank M.L. Gage for editorial comments.

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Correspondence to Fred H. Gage.

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Vadodaria, K.C., Stern, S., Marchetto, M.C. et al. Serotonin in psychiatry: in vitro disease modeling using patient-derived neurons. Cell Tissue Res 371, 161–170 (2018). https://doi.org/10.1007/s00441-017-2670-4

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Keywords

  • Human serotonergic neurons
  • Induced pluripotent stem cells
  • Mood disorders
  • Transdifferentiation
  • iSN
  • 5-HT
  • Depression
  • Bipolar