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Commentary, Novel Tools and Methods

Serotonin Neuronal Function from the Bed to the Bench: Is This Really a Mirrored Way?

Adeline Etievant, Thorsten Lau, Guillaume Lucas and Nasser Haddjeri
eNeuro 22 May 2019, 6 (3) ENEURO.0021-19.2019; DOI: https://doi.org/10.1523/ENEURO.0021-19.2019
Adeline Etievant
1Integrative and Clinical Neurosciences EA481, University of Bourgogne Franche-Comté, Besançon F-25000, France
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Thorsten Lau
2Department of Translation Brain Research, Central Institute for Mental Health, Medical Faculty Mannheim, Heidelberg University
3HITBR Hector Institute for Translational Brain Research gGmbH, Mannheim J5 68159, Germany
4German Cancer Research Center (DKFZ), Heidelberg INF280, Germany
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Guillaume Lucas
5Institut National de la Santé et de la Recherche Médicale, University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité, Neuronale, Unité 1215, Bordeaux F-33000, France
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Nasser Haddjeri
6Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, Bron F-69500, France
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  • firing activity
  • induced neurons
  • induced pluripotent stem cells
  • reprogramming
  • serotonin
  • translation

Significance Statement

Induced pluripotent stem cells (iPSCs) offer a great opportunity to recapitulate both normal and pathologic development of brain tissues. Recently, three research teams have developed human-PSC technology and direct somatic cell reprogramming to allow induction of human serotonin (5-hydroxytryptamine; 5-HT) neurons in vitro. While preclinical studies have repeatedly shown that 5-HT suppresses 5-HT neuronal firing activity, one group has tested the effect of 5-HT on the neuronal activity of those 5-HT-like cells and found a paradoxical excitatory action of 5-HT. Here, we argue that few cautions in translational interpretations have to be taken into account. Nonetheless, using patient-derived cells for generating disease relevant cell types truly offers a new and powerful approach for investigating mechanisms playing fundamental roles in psychiatric disorders.

Disease modeling by direct reprogramming into desired cell types represents a new huge challenge. Induced pluripotent stem cells (iPSCs), cells reprogrammed from human somatic cells, offer a great opportunity to recapitulate both normal and pathologic development of brain tissues and may as well provide essential strategies toward cell-based therapy of neuropsychiatric diseases (Vadodaria et al., 2018). Successfully, in 2016, three research teams have developed human-PSC technology (Lu et al., 2016) and direct somatic cell reprogramming (Vadodaria et al., 2016a; Xu et al., 2016) to allow induction of human serotonin neurons in vitro for the first time (for review, see Vadodaria et al., 2016b).

Remarkably, Lu et al. (2016) have demonstrated the accurate timely regulation of WNT, SHH, and FGF4 signaling pathways during the serotonergic (5-HT) neuron differentiation and generated an enriched population of 5-HT neurons from human embryonic stem cells (ESCs) and iPSCs. These human …

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eneuro: 6 (3)
eNeuro
Vol. 6, Issue 3
May/June 2019
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Serotonin Neuronal Function from the Bed to the Bench: Is This Really a Mirrored Way?
Adeline Etievant, Thorsten Lau, Guillaume Lucas, Nasser Haddjeri
eNeuro 22 May 2019, 6 (3) ENEURO.0021-19.2019; DOI: 10.1523/ENEURO.0021-19.2019

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Serotonin Neuronal Function from the Bed to the Bench: Is This Really a Mirrored Way?
Adeline Etievant, Thorsten Lau, Guillaume Lucas, Nasser Haddjeri
eNeuro 22 May 2019, 6 (3) ENEURO.0021-19.2019; DOI: 10.1523/ENEURO.0021-19.2019
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Keywords

  • firing activity
  • induced neurons
  • induced pluripotent stem cells
  • reprogramming
  • serotonin
  • translation

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