Activity-dependent control: neural progenitor cell fate

活动依赖性控制：神经祖细胞命运

• 批准号: 7090009
• 负责人: MIRJANA MALETIC-SAVATIC
• 金额: $ 17.47万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-05 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7090009
• 关键词: AMPA receptors; NMDA receptors; cell differentiation; cell proliferation; confocal scanning microscopy; dentate gyrus; electrophysiology; electrostimulus; genetic promoter element; genetically modified animals; green fluorescent proteins; histology; immunocytochemistry; laboratory mouse; neuroanatomy; neurogenesis; neurons; northern blottings; polymerase chain reaction; protein structure function; receptor expression; stem cells; tissue /cell culture

DESCRIPTION (provided by applicant): Neurogenesis, a process first thought to be limited to the prenatal period, occurs throughout life in distinct brain regions, such as the subventricular zone and the dentate gyrus subgranular zone. Over the past decade, a considerable amount of data has been accumulated regarding the identification, isolation, propagation and pluripotency of neural progenitor cells. However, little is known about the specific mechanisms that commit differentiation of progenitor cells toward a specific cell lineage, such as the neuronal or glial lineage. We propose to investigate the role of electrical activity in neural progenitor cell proliferation, differentiation and circuit formation, addressing our questions specifically to the dentate gyrus progenitor cell population. Our hypothesis is that electrical activity drives differentiation of dentate progenitor cells into the neuronal lineage, acting through fine modulation of glutamate receptor expression and activation. We propose to study these mechanisms in the adult organotypic hippocampal slice culture using transgenic mice that help us to identify the specific cell populations, electrophysiology to identify the profiles of undifferentiated and differentiated cells and two-photon microscopy to monitor morphological changes associated with electrical stimulation. Our objectives have a direct impact on the therapeutic use of neural progenitor cells in a variety of neurological disorders. An ability to identify specific factors that influence the differentiation of neural progenitor cells in vivo should provide us with important insights into the potential for endogenous and exogenous activation of progenitor cells, neurogenesis and the utility of dentate progenitor cells as agents for brain tissue reorganization and repair.

描述（由申请人提供）：神经发生，最初被认为仅限于产前时期的过程，在整个生命过程中发生在不同的大脑区域，例如脑室下区和齿状回颗粒下区。在过去的十年中，已经积累了大量关于神经祖细胞的鉴定、分离、增殖和多能性的数据。然而，人们对祖细胞分化为特定细胞谱系（例如神经元或神经胶质谱系）的具体机制知之甚少。我们建议研究电活动在神经祖细胞增殖、分化和电路形成中的作用，专门针对齿状回祖细胞群解决我们的问题。我们的假设是，电活动通过谷氨酸受体表达和激活的精细调节来驱动齿状祖细胞分化为神经元谱系。我们建议使用转基因小鼠研究成人器官型海马切片培养中的这些机制，帮助我们识别特定的细胞群，使用电生理学来识别未分化和分化细胞的概况，以及使用双光子显微镜来监测与电刺激相关的形态变化。我们的目标对神经祖细胞在各种神经系统疾病中的治疗用途有直接影响。识别体内影响神经祖细胞分化的特定因素的能力应该为我们提供关于祖细胞内源性和外源性激活的潜力、神经发生以及齿状祖细胞作为脑组织重组和修复剂的用途的重要见解。 。