TARGET FACULTY ANDRES/THE ROLE OF NOTCH IN ADULT NEUROPLASTICITY

目标教授安德烈斯/Notch 在成人神经可塑性中的作用

• 批准号: 7610091
• 负责人: ANDREW J ANDRES
• 金额: $ 18.26万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610091
• 关键词: Adult; Aging; Biological Assay; Biological Models; Brain region; Chromosome Pairing; Computer Retrieval of Information on Scientific Projects Database; Condition; Critical Pathways; Defect; Dendritic Spines; Development; Disease; Drosophila genus; Environment; Evolution; Faculty; Funding; Genes; Genetic; Grant; Human; Impairment; Individual; Injury; Insecta; Institution; Investigation; Life Experience; Longevity; Maintenance; Memory; Mitotic; Modeling; Molecular; Nervous system structure; Neurites; Neurologic; Neuronal Plasticity; Neurons; Organism; Pathology; Pathway interactions; Plastics; Research; Research Personnel; Resources; Role; Sensory; Signal Pathway; Signal Transduction; Source; Stimulus; Structure; Synapses; United States National Institutes of Health; Vertebrates; Work; fly; long term memory; notch protein; relating to nervous system; research study; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In previous work, Dr. Andres lab has defined a role for Notch function in the integrity of the adult nervous system of Drosophila. Flies in which Notch is conditionally compromised display neurological defects that included a reduced life span, uncoordinated flight, and an impairment of long-term memory. Experiments were performed in adult flies after the nervous system was fully developed and non-mitotic. The lab's hypothesis is that Notch is necessary for neuroplasticity in differentiated neurons. Plasticity in this context is defined as the acquisition or maintenance of neural structures (dendritic spines, neurites, synapses) in order to functionally deal with the individual organism's unique set of life experiences. Plastic regions of the brain would be expected to have a dynamic neuroarchitecture depending on such conditions as sensory inputs from environments rich in stimuli, attrition of unused neural connections, or injury. Drosophila is an ideal model system for these investigations for two reasons. First, the molecular pathways contributing to Drosophila development and aging can be dissected using powerful genetic tools to assay the important functional genes. Second, many of these critical pathways are conserved through evolution from insects to vertebrates, and Drosophila has made substantial contributions to the current understanding of signaling pathways and disease pathologies associated with the nervous system in humans. Thus, Dr. Andres proposes us investigating the hypothesis that the major role of Notch signaling in the adult nervous system is to contribute to plastic functions that include memory, and that we can use Drosophila to model important aspects of Notch signaling that might impact our understanding of neurological defects including Alzhemier's disease.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在之前的工作中，安德烈斯博士的实验室已经定义了Notch功能在果蝇成年神经系统完整性中的作用。Notch有条件地受损的果蝇表现出神经缺陷，包括寿命缩短，飞行不协调，以及长期记忆受损。在神经系统完全发育且无有丝分裂后，在成年果蝇身上进行实验。该实验室的假设是Notch对于分化神经元的神经可塑性是必要的。在这种情况下，可塑性被定义为获得或维持神经结构(树突、神经突、突触)，以便从功能上处理个体有机体的一套独特的生命经验。大脑的可塑性区域预计会有一个动态的神经结构，这取决于来自丰富刺激环境的感觉输入、未使用的神经连接的磨损或损伤等条件。果蝇是这些研究的理想模型系统，原因有两个。首先，可以使用强大的遗传工具来分析重要的功能基因，从而剖析导致果蝇发育和衰老的分子途径。其次，许多关键途径在从昆虫到脊椎动物的进化过程中是保守的，果蝇对目前了解与人类神经系统相关的信号通路和疾病病理做出了实质性贡献。因此，安德烈斯博士建议我们研究一种假设，即Notch信号在成人神经系统中的主要作用是促进包括记忆在内的可塑性功能，而且我们可以用果蝇来模拟Notch信号的重要方面，这些方面可能会影响我们对包括阿尔兹迈尔氏病在内的神经系统缺陷的理解。