ALCOHOL EFFECTS ON GANGLIOSIDE DEPENDENT NEUROGENESIS

神经发生支配发育性迁移、轴突形成和树突形成 神经元树枝状，实验中异常的中枢神经系统现象 Fas.神经发生机械地依赖于质膜)L 基质层粘连；2)神经细胞膜延长。简单的 神经节苷脂GM3和GD3促进质膜整合素调节和 碳水化合物剪切调节的底物粘附性。GM3/GD3的合成 IC-高尔基体外源唾液酸基转移酶在 EGF诱导的回收内小体，由EGF诱导形成 内吞作用，可能是促进黏附的一种独特的神经机制，通过 产生质膜GM3/GD3的靶向定位。慢性 细胞暴露于乙醇可降低EGF受体(EGFR)的内吞作用，从而 限制内体GM3/GD3重新剪裁，减弱黏附位点。这个 慢性酒精暴露对EGFR诱导的GM3/GD3唾液酸化的影响 无论是在鸡神经元培养中还是在体内，内小体都是定量的。 Ovo Fas模型。 轴突质膜延伸需要在质膜上添加 具有非常高结构的高尔基体衍生的质膜元件 神经源性(末端唾液酸神经节苷脂神经酰胺)含量 神经节苷脂糖体，特别是主要的神经节苷脂GT1b、GQ1b 细胞骨架抑制导致神经发生减弱 GT1B、GQ1b顺行高尔基体生物合成的调控。剂量和时间- 依赖慢性乙醇对这些物质生物合成的抑制作用 神经节苷脂在神经元培养中的作用和卵子Fas中的平行完整胚胎 模型将用[~3H]ManNAc作为专性唾液酸进行示踪 前身。 胚胎中枢神经系统神经元分化对慢性易感性的研究 乙醇对关键神经元唾液酸化的生物合成抑制作用 神经节苷脂将被详细记录。将对以下项目进行评估 外源性神经细胞膜的再供应与建筑黑色 神经节苷脂(GT1b/GQ1b)在神经细胞培养和培养中的作用 B)在体内胚胎鸡脑中，在长期接触乙醇的过程中。

Neuritogenesis governs developmental migration, axonogenesis and dendritic arborization of neurons, CNS phenomena which are aberrant in: experimental FAS. Neuritogenesis depends mechanistically upon l) plasma membrane- substratum adhesion and 2) neurital plasma membrane extension. The simple gangliosides GM3 and GD3 promote plasma membrane integrin-regulated and carbohydrate shear-modulated substrate adhesion. Synthesis of GM3/GD3 by IC-Golgi derived exofacial (ecto) sialyl transferases relocated within EGF-induced recycling endosomes, which are formed by EGF-induced endocytosis, may be a unique neuronal mechanism for promoting adhesion, by producing targeted localization of plasma membrane GM3/GD3. Chronic exposure of cells to ethanol reduces EGF-receptor (EGFR) endocytosis, thus limiting endosomal GM3/GD3 re-tailoring, and weakening adhesion loci. The effects of chronic ethanol exposure on GM3/GD3 sialylation in EGFR-induced endosomes will be quantitated in both a chick neuron culture and in an in ovo FAS model. Neurite plasma membrane extension requires addition to the plasma membrane of Golgi-derived plasma membrane elements with a very high structural content of neuritogenic (terminally-sialylated gangliotetraosyl ceramide) ganglioside glycoforms, particularly the major gangliosides GT1b, GQ1b Attenuated neuritogenesis results from inhibition of cytoskeletally regulated anterograde Golgi biosynthesis of GT1B, GQ1b. Dose-and time- dependent chronic ethanol-induced inhibition of biosynthesis of these gangliosides in neuron culture and a parallel whole embryo in ovo FAS model will be traced with [3H)ManNAc, as an obligate sialic acid precursor. Vulnerability of the differentiating embryonic CNS neuron to chronic ethanol-induced biosynthetic inhibition of sialylation of key neuronal gangliosides will be documented in detail. Evaluation will be made of exogenous re-supply of the neurital plasma membrane with building black gangliosides (GT1b/GQ1b) in neurite preservation A) in neuron culture and B) in vivo in embryonic chick brain, during chronic exposure to ethanol.