Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College Street, Room 306, Toronto, ON, Canada.
Prostaglandins Leukot Essent Fatty Acids. 2010 Feb-Mar;82(2-3):141-5. doi: 10.1016/j.plefa.2009.11.003. Epub 2010 Jan 27.
Polyunsaturated fatty acids (PUFA), especially docosahexaenoic and arachidonic acids, as well as cholesterol are important for neural development and maintaining brain function. However, in contrast to cholesterol, the brain is unable to synthesize the required amounts of these PUFA de novo and requires a constant supply from plasma. Suggested pools of uptake include plasma unesterified PUFA or the uptake of PUFA-containing lipoproteins via lipoprotein receptors into endothelial cells of the blood brain barrier. Our study tested whether the very low density lipoprotein receptor (VLDLr) is necessary for maintaining brain PUFA and cholesterol concentrations. Moreover, since VLDLr knockout (VLDLr(-/-)) mice have been reported to have behavioural deficits, this study asked the question whether altered brain PUFA and cholesterol concentrations might be related to these deficits. VLDLr(-/-) and wild-type mice had ad libitum access to chow. At 7 weeks of age the mice were sacrificed, and the cortex, cerebellum, hippocampus, and the remainder of the brain were isolated for total fatty acid and cholesterol analyses. There were no differences in total lipid PUFA or cholesterol concentrations in any of the four brain regions between VLDLr(-/-) and wild-type mice. These findings demonstrate that the VLDLr is not necessary for maintaining brain PUFA concentrations and suggest that other mechanisms to transport PUFA into the brain must exist.
多不饱和脂肪酸(PUFA),特别是二十二碳六烯酸和花生四烯酸,以及胆固醇,对神经发育和维持大脑功能很重要。然而,与胆固醇不同的是,大脑无法从头合成所需量的这些 PUFA,并且需要从血浆中获得持续供应。建议的摄取池包括血浆未酯化的 PUFA 或通过脂蛋白受体摄取含有 PUFA 的脂蛋白进入血脑屏障的内皮细胞。我们的研究测试了极低密度脂蛋白受体(VLDLr)是否对于维持大脑 PUFA 和胆固醇浓度是必需的。此外,由于已经报道 VLDLr 敲除(VLDLr(-/-))小鼠具有行为缺陷,因此本研究提出了这样一个问题,即大脑中 PUFA 和胆固醇浓度的改变是否与这些缺陷有关。VLDLr(-/-)和野生型小鼠可以随意摄入饲料。在 7 周龄时,处死小鼠,分离大脑皮质、小脑、海马体和大脑其余部分,用于总脂肪酸和胆固醇分析。在 VLDLr(-/-)和野生型小鼠的四个脑区中,总脂质 PUFA 或胆固醇浓度没有差异。这些发现表明 VLDLr 对于维持大脑 PUFA 浓度不是必需的,并且表明必须存在其他将 PUFA 转运到大脑的机制。