Mauch D H, Nägler K, Schumacher S, Göritz C, Müller E C, Otto A, Pfrieger F W
Synapse Group and, Protein Chemistry Group, Max-Delbrück-Center for Molecular Medicine, D-13092 Berlin, Germany.
Science. 2001 Nov 9;294(5545):1354-7. doi: 10.1126/science.294.5545.1354.
The molecular mechanisms controlling synaptogenesis in the central nervous system (CNS) are poorly understood. Previous reports showed that a glia-derived factor strongly promotes synapse development in cultures of purified CNS neurons. Here, we identify this factor as cholesterol complexed to apolipoprotein E-containing lipoproteins. CNS neurons produce enough cholesterol to survive and grow, but the formation of numerous mature synapses demands additional amounts that must be provided by glia. Thus, the availability of cholesterol appears to limit synapse development. This may explain the delayed onset of CNS synaptogenesis after glia differentiation and neurobehavioral manifestations of defects in cholesterol or lipoprotein homeostasis.
目前人们对控制中枢神经系统（CNS）突触形成的分子机制了解甚少。先前的报告表明，一种神经胶质细胞衍生因子能强烈促进纯化的中枢神经系统神经元培养物中的突触发育。在此，我们确定该因子为与含载脂蛋白E的脂蛋白复合的胆固醇。中枢神经系统神经元产生足够的胆固醇以维持生存和生长，但大量成熟突触的形成需要神经胶质细胞提供额外的胆固醇。因此，胆固醇的可利用性似乎限制了突触发育。这或许可以解释神经胶质细胞分化后中枢神经系统突触形成的延迟起始，以及胆固醇或脂蛋白稳态缺陷的神经行为表现。
