ROLE OF GROWTH FACTORS IN BRAIN DEVELOPMENT

生长因子在大脑发育中的作用

• 批准号: 6572332
• 负责人: CHERYL F DREYFUS
• 金额: $ 8.64万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6572332
• 关键词: astrocytes; autocrine; autoradiography; cell cell interaction; developmental neurobiology; embryo /fetus culture; gene expression; glia; glial fibrillary acidic protein; glutamate receptor; growth factor receptors; immunocytochemistry; in situ hybridization; laboratory rat; neurogenesis; neuroregulation; neurotransmitters; neurotrophic factors; prosencephalon; receptor expression

The classic neurotrophin theory holds that distant targets provide survival factors to innervating neurons. However, we have found that local support cells may also be sources of these molecules. The current project uses the basal-forebrain medial septum (BF) as a critical model to explore the proposal that local neuron-astrocyte-neuron regulatory loops support survival and function of specific brain regions during development and maturity. Preliminary studies examining cultured BF neurons and astrocytes are the basis for the proposed work. We found that individual BF neural signals differentially regulate BF astrocytic gene expression of the neurotrophins, NGF, BDNF and NT3. These neurotrophins, in turn, differentially influence BF neuron survival, neurite extension and function, and, in related studies, regulate synaptic transmission and astrocyte morphology. To investigate the role of neuron-astrocyte-neuron regulatory loops we will 1) examine astrocyte development in the absence of BF neurons, 2) define regulation of astrocytes by neural signals, 3) evaluate autocrine regulation by neurotrophines, 4) compare astrocytes derived from embryonic day 17 to cells derived from postnatal day 1 and adults to define stage-specific astrocyte function, and 5) define physiologic consequences of mechanisms identified in culture by delineating the effects of the aforementioned neural signals and trophins on E17, P1 and adult BF in vivo. These studies are designed to explore local neuron-astrocyte-neuron regulation in the developing and mature BF. An understanding of this regulation will provide insights for optimization of survival and function of BF, a region that degenerates in Alzheimer's disease.

经典的神经营养理论认为，遥远的目标提供 神经元的生存因子。但是，我们发现本地 支持细胞也可能是这些分子的来源。当前项目 使用基底前脑内侧隔膜（BF）作为关键模型来探索 局部神经元 - 胃细胞 - 神经元调节环的支持 开发过程中特定大脑区域的生存和功能 到期。 培养的BF神经元和星形胶质细胞检查的初步研究是 拟议工作的基础。我们发现单个BF神经信号 差异调节BF星形胶质细胞基因表达 神经营养蛋白，NGF，BDNF和NT3。这些神经营养蛋白反过来 差异影响BF神经元存活，神经突扩展和 功能，在相关研究中，调节突触传播和 星形胶质细胞形态。调查神经元 - 胃细胞神经元的作用 调节环我们将1）在不存在的情况下检查星形胶质细胞的发展 BF神经元，2）通过神经信号定义对星形胶质细胞的调节，3） 评估神经营养素的自分泌调节，4）比较星形胶质细胞 从胚胎第17天到产后第1天衍生的细胞和 定义特异性星形胶质细胞功能的成年人，5）定义 通过文化中鉴定的机制的生理后果 描述上述神经信号和滋养蛋白的影响 在E17上，P1和成人BF在体内。 这些研究旨在探索当地的神经元腹腔静脉内神经元 发育中和成熟的BF中的调节。对此的理解 法规将提供优化生存和功能的见解 BF，一个在阿尔茨海默氏病中退化的地区。