Biochemistry & Pharmacology: Open Access
Open Access

Abstract

Self-Sufficient Stem Cells: Stem Cell-Derived Serotonergic Neurons Rely on Endogenous BDNF Release to Establish Serotonergic Networks during Terminal Differentiation

Eva Krause, Patrick Schloss and Thorsten Lau

The neurotransmitter serotonin plays an essential role in a variety of physiological processes including learning and memory, mood, and neuromodulation. Consequently, dysfunction of serotonergic neurotransmission is associated with psychiatric diseases such as depression, anxiety disorders, and schizophrenia. Because the small number and vast arborization of serotonergic neurons in vivo impede their use in primary cell culture, stem cell-derived serotonergic neurons are applied as in vitro-models for serotonergic neurotransmission. Among others, 1C11 stem cells are used to generate serotonergic neurons in vitro, for example, to analyze the effect of antidepressant treatment on serotonin re-uptake or the function of microRNAs in serotonergic neurons. Since 1C11 stem cells differentiate uniformly into serotonergic neurons, there is no need to optimize terminal differentiation. Therefore the contribution of neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), to terminal differentiation of 1C11 stem cells is currently unknown. To bridge this gap, we differentiated 1C11 stem cells and determined the effect of endogenous BDNF release as well as of supplemented recombinant BDNF on neurite growth. With regard to the application of recombinant BDNF we also differentiated 1C11 stem cells in microfluidic isolation devices in order to determine whether the location of recombinant BDNF application may exert differential effects on neurite growth. Our data showed that endogenously synthesized and released BDNF is sufficient to form functional neuritic networks during terminal differentiation and that an exogenous BDNF source did not extensively promote neurite growth. However, the location of recombinant BDNF application did affect the microgrooves targeting behaviour of differentiating 1C11 stem cells in microfluidic isolation devices. In summary, our data shows that 1C11 stem cells rely on synthesis and release of endogenous BDNF for serotonergic network formation during terminal differentiation.