CELL DEATH IN THE OLIGODENDROGLIAL LINEAGE

描述(摘自申请人的摘要) 程序性细胞死亡(PCD)，是许多人发育的正常部分 细胞类型，最近被证明发生在 少突胶质细胞谱系，可被蛋白质生长因子预防。 初步数据显示，这种细胞死亡可能发生在 少突胶质细胞谱系的阶段，即许多细胞被消灭 通过细胞凋亡，最常见的程序性细胞死亡方式 主要特征是核碎裂，而且增长 抑制这种死亡的因素以特定阶段的方式起作用。 在几个髓鞘脱失突变中也发现了细胞死亡。 在啮齿动物身上，以及在沃勒式视神经退化之后。 他们假设在这些细胞中程序性细胞死亡的加重 病理是少突胶质细胞枯竭的原因 通过适当的生长因子预防细胞死亡可以 改善这些条件。 他们将确定少突胶质细胞发育的哪个阶段(S) 血统最容易受到细胞死亡的影响，以及细胞凋亡是否 在沃勒氏变性和髓鞘缺乏症(MD)中增加 以及哪种生长因子最有效地抑制程序化细胞 体内和体外的死亡。他们将利用一种化验方法 检测核碎裂，可以与免疫表型相结合， 在体外和体内都效果很好。 他们的具体目标是：1.为了检查细胞死亡， 细胞凋亡，以及少突胶质细胞谱系的阶段 利用具有良好特征的大鼠脑白质在体外发生细胞凋亡 物质文化体系。然后他们将确定哪些增长因素 最好防止这种细胞死亡；2.评估细胞凋亡性死亡 体内的少突胶质系细胞；3.检验假设 沃勒氏病后少突胶质系细胞的耗竭 变性是少突胶质前体细胞凋亡的结果 由失去轴突接触所致。他们还将确定这是否 细胞凋亡可被通常由或分泌的生长因子抑制 在神经元上呈现；以及4.确定是否有增加 髓鞘缺陷大鼠处于什么发育阶段的细胞凋亡 细胞发生凋亡，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.