THE ROLE OF NOTCH IN ADULT NEUROPLASTICITY

NOTCH 在成人神经可塑性中的作用

• 批准号: 7725219
• 负责人: ANDREW J ANDRES
• 金额: $ 18.3万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725219
• 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; 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 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 studies have made substantial contributions to the current understanding of signaling pathways and disease pathologies associated with the nervous system in humans. Thus, Dr. Andres investigates 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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在以前的工作中，Andres博士定义了Notch功能在果蝇成年神经系统完整性中的作用。 有条件地损害Notch的苍蝇显示神经缺陷，包括寿命缩短，飞行不协调和长期记忆受损。 实验在神经系统完全发育且无有丝分裂的成年果蝇中进行。 该实验室的假设是，Notch是分化神经元的神经可塑性所必需的。 在这种情况下，可塑性被定义为获得或维持神经结构（树突棘，神经突，突触），以便在功能上处理个体生物体独特的生活经验。 大脑的可塑性区域应该具有动态的神经结构，这取决于来自刺激丰富的环境的感觉输入、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，原因有二。 首先，果蝇发育和衰老的分子途径可以使用强大的遗传工具来分析重要的功能基因。 其次，这些关键途径中的许多是通过从昆虫到脊椎动物的进化而保守的，果蝇的研究对目前理解与人类神经系统相关的信号通路和疾病病理做出了重大贡献。因此，Andres博士研究了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的假设，并且我们可以使用果蝇来模拟Notch信号的重要方面，这可能会影响我们对包括阿尔茨海默病在内的神经缺陷的理解。