Spicing up brain stem cells and brain function with neurotransmitters (SSA)

用神经递质 (SSA) 增强脑干细胞和大脑功能

• 批准号: 1654449
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1654449
• 关键词: Spicing; up; brain; stem; cells

New neurons are continuously generated in the adult brain from neural stem cells found in particular niches, through a process called adult neurogenesis. Active retention of these neurons and enhancement of adult neurogenesis is thought to benefit brain functions and protect against dementia and depression. Therefore, there is an avid search for factors and molecules that can promote adult neurogenesis. Neurotrasmitters, such as Acetylcholine, typically mediate trans-synaptic communication between neurons and their target organs. However, they also seem to play an unexpected role in adult neurogenesis by modulating the proliferation and differentiation of neural stem cells. Indeed, elderly patients treated with anti-cholinergic drugs for other ailments, appear to be more susceptible to cognitive decline. In part, these unexpected roles appear to involve classical growth factors such as the Fibroblast Growth Factor signalling system.This project aims to dissect the molecular partnerships that acetylcholine develops with growth factors to induce its beneficial effects on brain stem cells. This will be investigated using well-established in vitro model systems for neural stem cell growth, as well as brain slice cultures that preserve the stem cell niche architecture. In each of these systems, we will profile the key players and components, and using molecular and transgenic mouse models test their contribution and significance to adult neurogenesis. In addition to generic training skills, through these studies, the applicant will become proficient in a host of cellular and molecular techniques, including immunolabelling, gene-profiling and cloning, brain culture and high-resolution time-lapse imaging. Combined, these studies will prepare a candidate for a research career in molecular neurosciences.

在成人大脑中，新的神经元不断地从特定的神经龛中发现的神经干细胞中产生，这一过程被称为成人神经发生。这些神经元的活跃保留和成人神经发生的增强被认为有益于大脑功能，并防止痴呆和抑郁症。因此，迫切需要寻找能够促进成人神经发生的因子和分子。神经递质，如乙酰胆碱，通常介导神经元和目标器官之间的跨突触通讯。然而，它们似乎也通过调节神经干细胞的增殖和分化，在成人神经发生中发挥了意想不到的作用。事实上，服用抗胆碱能药物治疗其他疾病的老年患者似乎更容易出现认知能力下降。在某种程度上，这些意想不到的作用似乎涉及到经典的生长因子，如成纤维细胞生长因子信号系统。本项目旨在剖析乙酰胆碱与生长因子形成的分子伙伴关系，从而诱导其对脑干细胞的有益作用。这将使用成熟的体外神经干细胞生长模型系统，以及保存干细胞生态位结构的脑切片培养来进行研究。在这些系统中，我们将分析关键参与者和组成部分，并使用分子和转基因小鼠模型测试它们对成人神经发生的贡献和意义。除了通用的培训技能，通过这些研究，申请人将精通大量的细胞和分子技术，包括免疫标记，基因分析和克隆，大脑培养和高分辨率定时成像。综合起来，这些研究将为分子神经科学研究生涯的候选人做好准备。