CELL DEATH IN THE OLIGODENDROGLIAL LINEAGE

描述（来自申请人摘要） 程序性细胞死亡（PCD）是许多细胞发育的正常部分， 细胞类型，最近已被证明发生在细胞的 少突胶质细胞谱系，并可通过蛋白质生长因子预防。 初步数据表明，这种细胞死亡可能发生在几个 少突胶质细胞谱系的阶段，许多细胞被消除 通过细胞凋亡，程序性细胞死亡的最常见的方法 其主要特征是核碎裂， 抑制这种死亡的因素以阶段特异性方式起作用。 在几种髓鞘形成障碍突变中也检测到细胞死亡 在啮齿类动物和以下沃勒变性的视神经。 他们假设，这些细胞中程序性细胞死亡的加重， 病理学导致少突胶质细胞耗竭， 通过适当的生长因子预防细胞死亡， 改善这些条件。 他们将确定寡腺胶质细胞的发育阶段 谱系最容易受到细胞死亡的影响，而细胞凋亡是否 在沃勒变性和髓磷脂缺乏（MD）期间增加 哪些生长因子最有效地抑制编程细胞 体内和体外的死亡。他们将使用一种检测方法， 检测核碎裂，可以与免疫分型相结合， 并且在体外和体内都工作良好。 他们的具体目标是：1。为了检测细胞死亡， 细胞凋亡，以及少突胶质细胞谱系的阶段， 细胞凋亡发生在体外使用良好表征的大鼠大脑白色 物质文化系统然后他们将确定哪些增长因素 最好防止这种细胞死亡; 2.为了评估细胞凋亡， 体内少突胶质细胞系细胞。3.为了验证这个假设， Wallerian后寡腺胶质细胞谱系细胞的耗竭 退化是少突胶质细胞前体细胞凋亡的结果 是由轴突接触丧失引起的他们还将确定， 细胞凋亡可被正常由细胞分泌的生长因子抑制， 在神经元上呈现;以及4.为了确定是否有增加， 髓鞘缺乏大鼠的细胞凋亡，在发育的哪个阶段 细胞凋亡发生，如果生长因子可以减少这种细胞死亡。

DESCRIPTION (from applicant's abstract) Programmed cell death (PCD), a normal part of the development of many cell types, has recently been shown to occur in cells of the oligodendroglial lineage and can be prevented by protein growth factors. Preliminary data suggests that this cell death may occur at several stages of the oligodendroglial lineage, that many cells are eliminated by apoptosis, the most common method of programmed cell death characterized primarily by nuclear fragmentation, and that the growth factors which inhibit this death operate in a stage specific manner. Cell death also has been detected in several dysmyelinating mutations in rodents and following Wallerian degeneration of the optic nerve. They hypothesize that accentuation of programmed cell death in these pathologies is responsible for oligodendroglial depletion and that prevention of cell death by the appropriate growth factors could ameliorate these conditions. They will determine which stage(s) of development of the oligodenroglial lineage is most vulnerable to cell death, and whether apoptosis is increased during Wallerian degeneration and in the myelin deficient (MD) rat, and which growth factors most effectively inhibit programmed cell death both in vivo and in vitro. They will utilize an assay which detects nuclear fragmentation, can be combined with immunophenotyping, and works well both in vitro and in vivo. Their specific aims are: 1. To examine cell death, the amount of apoptosis, and the stages of the oligodendroglial lineage at which apoptosis occurs in vitro using a well characterized rat cerebral white matter culture system. Then they will determine which growth factors best prevent this cell death; 2. To assess apoptotic cell death of oligodendroglial lineage cells in vivo.; 3. To test the hypothesis that the depletion of the oligodenroglial lineage cells following Wallerian degeneration is a consequence of oligodendrocyte precursor apoptosis caused by loss of axonal contact. They will also determine if this apoptosis can be inhibited by growth factors normally secreted by or presented on neurons; and 4. To ascertain if there is an increase in apoptosis in myelin deficient rats, at what stage of development apoptosis occurs, and if growth factors can decrease this cell death.