As one major component of extracellular matrix (ECM) in the central nervous system, chondroitin sul- fate proteoglycans (CSPGs) have long been known as inhibitors enriched in the glial scar that prevent axon regen...As one major component of extracellular matrix (ECM) in the central nervous system, chondroitin sul- fate proteoglycans (CSPGs) have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite out- growth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron (CGN) culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, in- cluding cell adhesion, spreading and neurite growth. Neurite length decreased while CSPGs concentration arised, meanwhile, a decrease in cell density accompanied by an increase in cell aggregates formation was observed. Soluble CSPGs also showed an inhibition on neurite outgrowth, but it required a higher concen- tration to induce cell aggregates formation than coated CSPGs. We also found that growth cone size was significantly reduced on CSPGs and neuronal cell spreading was restrained by CSPGs, attributing to an inhibition on lamellipodial extension. The effect of CSPGs on neuron adhesion was further evidenced by interference reflection microscopy (IRM) which directly demonstrated that both CGNs and cerebral cortical neurons were more loosely adherent to a CSPG substrate. These data demonstrate that CSPGs have an effect on cell adhesion and spreading in addition to neurite outgrowth.展开更多
During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generall...During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generally thought that these progenitor cells sequentially produce neurons followed by glia.展开更多
基金supported by the National Natural Science Foundation of China,No.81601066the Natural Science Foundation of Guangdong Province of China,No.2017A030313103 and 2016A030313096+2 种基金a grant from the Program of Introducing Talents of Discipline to Universities,No.B14036the Fundamental Research Funds for the Central Universities,No.21616340the Division of Intramural Research of the National Heart,Lung,and Blood Institute of National Institutes of Health
文摘As one major component of extracellular matrix (ECM) in the central nervous system, chondroitin sul- fate proteoglycans (CSPGs) have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite out- growth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron (CGN) culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, in- cluding cell adhesion, spreading and neurite growth. Neurite length decreased while CSPGs concentration arised, meanwhile, a decrease in cell density accompanied by an increase in cell aggregates formation was observed. Soluble CSPGs also showed an inhibition on neurite outgrowth, but it required a higher concen- tration to induce cell aggregates formation than coated CSPGs. We also found that growth cone size was significantly reduced on CSPGs and neuronal cell spreading was restrained by CSPGs, attributing to an inhibition on lamellipodial extension. The effect of CSPGs on neuron adhesion was further evidenced by interference reflection microscopy (IRM) which directly demonstrated that both CGNs and cerebral cortical neurons were more loosely adherent to a CSPG substrate. These data demonstrate that CSPGs have an effect on cell adhesion and spreading in addition to neurite outgrowth.
基金the Natural Science Foundation of Zhejiang Province(LQ19C090001)the National Natural Science Foundation of China(31900703 and 31771621).
文摘During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generally thought that these progenitor cells sequentially produce neurons followed by glia.