Waider Jonas, Ziegler Janina, Lau Thorsten
Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
Central Institute of Mental Health, Hector Institute for Translational Brain Research, Medical Faculty Mannheim, University Heidelberg, Heidelberg, Germany.
Stem Cell Investig. 2016 Dec 19;3:94. doi: 10.21037/sci.2016.11.12. eCollection 2016.
Recently, Trista North and colleagues showed that neuronal synthesis of serotonin is an essential key process for embryonic hematopoietic stem (HPS) cell production in zebrafish. Using their experimental design, they were able to show that neuronal serotonin activates the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid receptor activity which in turn induces HPS cell formation. In our perspective, we give a short overview on established experimental approaches for serotonergic neurotransmission and and their potential to address putative contributions of serotonergic neurotransmission to physiological processes beyond the central nervous systems (CNS). We briefly introduce common features of brain serotonin-depleted, tryptophan hydroxylase-2 knockout mice, which can be applied to investigate the contribution of brain-derived serotonin to developmental and adult physiological processes outside the CNS. These models allow to analyzing gender-specific, HPA axis-dependent processes in female and male knockout mice during developmental and adult stages. We also highlight the application of human and mouse stem cell-derived serotonergic neurons as an independent research model as well as complementary experimental approach to transgenic animal models. In case of human serotonergic neurotransmission, human -generated neurons present a very promising and highly valuable experimental approach to address characteristics of human neuronal serotonin signaling on a molecular and cellular level. The combination of transgenic animal models and newly established stem cell technologies will provide powerful research platforms, which will help to answer yet unsolved mysteries of serotonergic neurotransmission.
最近，特里斯坦·诺思及其同事表明，血清素的神经元合成是斑马鱼胚胎造血干细胞（HPS）产生过程中的一个关键必要步骤。通过他们的实验设计，他们能够证明神经元血清素会激活应激反应性下丘脑-垂体-肾上腺（HPA）轴以及糖皮质激素受体活性，进而诱导HPS细胞形成。从我们的角度来看，我们简要概述了已确立的血清素能神经传递实验方法，以及它们在探究血清素能神经传递对中枢神经系统（CNS）以外生理过程的假定作用方面的潜力。我们简要介绍了脑血清素缺乏的色氨酸羟化酶-2基因敲除小鼠的共同特征，这些特征可用于研究脑源性血清素对CNS以外发育和成年生理过程的作用。这些模型能够分析发育和成年阶段雌性和雄性基因敲除小鼠中性别特异性的、HPA轴依赖性的过程。我们还强调了将人类和小鼠干细胞衍生的血清素能神经元作为一种独立的研究模型以及对转基因动物模型的补充实验方法的应用。就人类血清素能神经传递而言，人类产生的神经元是一种非常有前景且极有价值的实验方法，可用于在分子和细胞水平上研究人类神经元血清素信号传导的特征。转基因动物模型与新建立的干细胞技术的结合将提供强大的研究平台，这将有助于解答血清素能神经传递尚未解决的谜团。
