NEURITE OUTGROWTH ON A STEP GRADIENT OF CHONDROITIN SULFATE PROTEOGLYCAN (CS-PG)
NEURITE OUTGROWTH ON A STEP GRADIENT OF CHONDROITIN SULFATE PROTEOGLYCAN (CS-PG)
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DOI：
10.1002/neu.480230311
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发表时间：
1992-04-01
期刊：
影响因子：
--
通讯作者：
LETOURNEAU, PC
中科院分区：
文献类型：
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作者：
SNOW, DM;LETOURNEAU, PC
硫酸化蛋白聚糖（PG）可能在神经突生长的调节中发挥重要作用。它们存在于发育中的神经系统的无轴突区域，并在体外以浓度依赖性方式排斥伸长的神经突。添加生长促进分子，例如层粘连蛋白，可以改变 PG 对神经突生长的抑制作用（Snow、Steindler 和 Silver，1990b）。含有高 PG/低层粘连蛋白比例的基质完全抑制神经突生长，而在低 PG/高层粘连蛋白基质上观察到正常、无阻碍的生长。因此，不同的神经突生长模式可能是由生长促进分子与生长抑制分子的比例调节引起的。使用视频显微镜，分析了胚胎鸡背根神经节神经元（DRG）、鸡视网膜神经节神经元（RGC）和大鼠前脑神经元（FB），因为它们将过程从仅由层粘连蛋白组成的基质延伸到与层粘连蛋白结合的硫酸软骨素蛋白多糖（CS-PG）浓度递增的阶梯梯度。与发生在高浓度 CS-PG 的单条带边界处的神经突生长抑制相反（Snow 等人，1990b 和本研究），生长锥生长到 CS-PG 上并向上生长，呈逐步分级分布。尽管不同细胞类型的行为是独特的，但每种细胞类型的共同行为是随着CS-PG浓度的增加，神经突生长速率降低。这些数据表明，适当浓度的生长促进分子与生长抑制分子组合可以调节体内神经突生长的方向和可能的时间。不同神经元类型的不同反应表明硫酸化PG的存在可能对神经元发育的不同方面产生不同的影响。
Sulfated Proteoglycans (PGs) may play a significant role in the regulation of neurite outgrowth. They are present in axon-free regions of the developing nervous system and repel elongating neurites in a concentration-dependent manner in vitro. The addition of growth-promoting molecules, such as laminin, can modify the inhibitory effect of PGs on neurite outgrowth (Snow, Steindler, and Silver, 1990b). Substrata containing a high-PG/low-laminin ratio completely inhibit neurite outgrowth, while normal, unimpeded outgrowth is observed on low-PG/high-laminin substrata. Therefore, different patterns of neurite outgrowth may result from regulation of the ratio of growth-promoting molecules to growth-inhibiting molecules. Using video microscopy, embryonic chicken dorsal root ganglia neurons (DRG), chicken retinal ganglia neurons (RGC), and rat forebrain neurons (FB) were analyzed as they extended processes from a substratum consisting of laminin alone onto a step gradient of increasing concentrations of chondroitin sulfate proteoglycan (CS-PG) bound to laminin. In contrast to neurite outgrowth inhibition that occurs at the border of a single stripe of high concentration of CS-PG (Snow et al., 1990b and this study), growth cones grew onto and up CS-PG presented in a step-wise graded distribution. Although the behavior of the different cell types was unique, a common behavior of each cell type was a decrease in the rate of neurite outgrowth with increasing CS-PG concentration. These data suggest that appropriate concentrations of growth-promoting molecules combined with growth-inhibiting molecules may regulate the direction and possibly the timing of neurite outgrowth in vivo. The different responses of different neuronal types suggest that the presence of sulfated PG may have varying effects on different aspects of neuronal development.