NEUROTROPHINS AND OLIGODENDROCYTE FUNCTION

本提案的目标是界定以下方面的作用： 少突胶质细胞，传统的中枢神经髓鞘细胞 系统，作为生产者的营养分子在发展过程中。 在这 能力，假设少突胶质细胞产生NGF，BDNF， NT3，影响少突胶质细胞存活和功能的分子，如 以及局部神经元。 局部神经元反过来调节少突胶质细胞 功能 提示临界自分泌和旁分泌 可能存在相互作用以优化少突胶质细胞的存活和功能 和相关的神经元。 这一问题将在少突胶质细胞群体中得到解决， 基底前脑，一个众所周知对神经营养因子敏感的区域。 初步研究表明，这种少突胶质细胞表达 并对神经营养素有反应，受神经信号调节。 到 研究少突胶质细胞作为营养素生产者的作用， 1)检查作为营养素生产者的少突胶质细胞的成熟， 在培养物中发育期间的营养因子应答者，2）研究影响 神经营养因子分子对少突胶质细胞成熟的影响，3）定义 少突胶质细胞对基底前脑神经元的调节，4）定义 神经信号对少突胶质细胞发育的作用，以及5）确定 培养物中的效应是否与体内相关。 这些研究旨在探索少突胶质细胞的作用， 营养分子、NGF、BDNF和NT 3的提供者。 拟将 这些神经营养因子为少突胶质细胞提供营养支持， 局部神经元群体。 这些研究将确定支持 少突胶质细胞功能 因此，他们承诺提供新的见解， 脱髓鞘疾病中可能出现的缺陷。

DESCRIPTION The goal of this proposal is to define the role of oligodendrocytes, the traditional myelinating cells of the central nervous system, as producers of trophic molecules during development. In this capacity, it is hypothesized that oligodendrocytes produce NGF, BDNF, and NT3, molecules that affect survival and function of oligodendrocytes, as well as local neurons. Local neurons, in turn, regulate oligodendrocyte function. It is suggested that critical autocrine and paracrine interactions may exist to optimize survival and function of oligodendrocytes and related neurons in specific brain regions. This issue will be addressed in oligodendrocyte populations associated with the basal forebrain, a region well-known to be sensitive to neurotrophins. Preliminary studies suggest that this oligodendrocyte population expresses and responds to neurotrophins and is regulated by neural signals. To investigate the role of oligodendrocytes as trophin producers the study will 1) examine the maturation of oligodendrocytes as trophin producers and trophin responders during development in culture, 2) investigate the effects of neurotrophin molecules on oligodendrocyte maturation, 3) define regulation of basal forebrain neurons by oligodendrocytes, 4) define the role of neural signaling on oligodendrocyte development, and 5) determine whether effects in culture are relevant in vivo. These studies are designed to explore the role of oligodendrocyte as providers of the trophic molecules, NGF, BDNF, and NT3. It is proposed that these neurotrophins provide trophic support for oligodendrocytes as well as local neuronal populations. The studies will identify factors that support oligodendrocyte function. As such, they promise to provide new insights into deficits that may occur in demyelinating diseases.