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The role of serotonin in motor neuron development and regeneration

血清素在运动神经元发育和再生中的作用

基本信息

批准号：
BB/I01294X/1
负责人：
Catherina Becker
金额：
$ 47.82万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FI01294X%2F1
关键词：
role serotonin motor neuron development

项目摘要

Motor neurons are the cell type that mediates all movement signals from the brain to the muscles. In neurodegenerative diseases, such as ALS, these cells are lost, leading to paralysis and death of patients. We have previously shown that, in contrast to humans, adult zebrafish can replace lost neurons from stem cells that are present in the spinal cord. Although adult mammals possess these cells, which give rise to motor neurons during development, they apparently to not receive the right signals for motor neuron differentiation at the adult stage. We study the role of the neurotransmitter serotonin in development and regeneration of motor neurons in zebrafish. We found that serotonin stimulates motor neuron development in embryos and we now want to test whether this is also the case during adult regeneration. We will also identify the receptor molecules necessary for the action of serotonin. We have previously shown that signals involved in motor neuron development in zebrafish embryos have similar actions on motor neuron generation from human stem cells. This indicates that results from zebrafish are relevant to the human situation. Thus we aim to elucidate a new signal that could ultimately be harnessed to replace motor neurons in ALS, by differentiating transplantable or endogenous stem cells into motor neurons.

运动神经元是一种将所有运动信号从大脑传递到肌肉的细胞类型。在神经退行性疾病中，如肌萎缩侧索硬化症，这些细胞丢失，导致患者瘫痪和死亡。我们之前已经证明，与人类相比，成年斑马鱼可以取代脊髓中存在的干细胞中丢失的神经元。尽管成年哺乳动物拥有这些细胞，这些细胞在发育过程中会产生运动神经元，但它们显然没有在成年阶段接收到正确的运动神经元分化信号。我们研究了神经递质5-羟色胺在斑马鱼运动神经元发育和再生中的作用。我们发现5-羟色胺能刺激胚胎中运动神经元的发育，现在我们想要测试在成人再生过程中是否也是如此。我们还将确定5-羟色胺作用所必需的受体分子。我们之前已经证明，斑马鱼胚胎中参与运动神经元发育的信号在人类干细胞生成运动神经元方面也有类似的作用。这表明斑马鱼的结果与人类的情况有关。因此，我们的目标是阐明一种新的信号，通过将可移植或内源性干细胞分化为运动神经元，最终可以利用该信号来取代ALS中的运动神经元。