Nieweg Katja, Schaller Hubert, Pfrieger Frank W
Department of Neurotransmission, Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, Strasbourg, France.
J Neurochem. 2009 Apr;109(1):125-34. doi: 10.1111/j.1471-4159.2009.05917.x. Epub 2009 Feb 20.
Neurons have a high demand for cholesterol to develop and maintain membrane-rich structures like axons, dendrites and synapses, but it remains unclear, whether they can satisfy their need by costly de novo synthesis. To address this, we compared cholesterol synthesis in serum-free cultures of highly purified CNS neurons and glial cells from postnatal rats. We observed marked cell-specific differences: Compared with glial cells, neurons showed different profiles of biosynthetic enzymes, post-squalene precursors and cholesterol metabolites, and they produced cholesterol less efficiently, possibly because of very low levels of lanosterol-converting enzymes. Astrocytes responded to inhibition of cholesterol synthesis with a much stronger up-regulation of biosynthetic enzymes than neurons. Our results support the idea that neurons cannot produce cholesterol efficiently and that they depend on an external source of this lipid.
神经元对胆固醇的需求量很高，以发育和维持富含膜的结构，如轴突、树突和突触，但它们是否能够通过代价高昂的从头合成来满足自身需求仍不清楚。为了解决这个问题，我们比较了新生大鼠高度纯化的中枢神经系统神经元和神经胶质细胞在无血清培养中的胆固醇合成情况。我们观察到明显的细胞特异性差异：与神经胶质细胞相比，神经元的生物合成酶、角鲨烯后体和胆固醇代谢物的谱不同，并且它们产生胆固醇的效率较低，这可能是因为羊毛甾醇转化酶的水平非常低。星形胶质细胞对胆固醇合成抑制的反应是生物合成酶的上调比神经元强得多。我们的结果支持这样的观点，即神经元不能有效地产生胆固醇，并且它们依赖于这种脂质的外部来源。
