Wurtman Richard J, Ulus Ismail H, Cansev Mehmet, Watkins Carol J, Wang Lei, Marzloff George
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar Street, 46-5023B MIT, Cambridge, MA 02139, USA.
Brain Res. 2006 May 9;1088(1):83-92. doi: 10.1016/j.brainres.2006.03.019. Epub 2006 Apr 21.
The synthesis of brain phosphatidylcholine may utilize three circulating precursors: choline; a pyrimidine (e.g., uridine, converted via UTP to brain CTP); and a PUFA (e.g., docosahexaenoic acid); phosphatidylethanolamine may utilize two of these, a pyrimidine and a PUFA. We observe that consuming these precursors can substantially increase membrane phosphatide and synaptic protein levels in gerbil brains. (Pyrimidine metabolism in gerbils, but not rats, resembles that in humans.) Animals received, daily for 4 weeks, a diet containing choline chloride and UMP (a uridine source) and/or DHA by gavage. Brain phosphatidylcholine rose by 13-22% with uridine and choline alone, or DHA alone, or by 45% with the combination, phosphatidylethanolamine and the other phosphatides increasing by 39-74%. Smaller elevations occurred after 1-3 weeks. The combination also increased the vesicular protein Synapsin-1 by 41%, the postsynaptic protein PSD-95 by 38% and the neurite neurofibrillar proteins NF-70 and NF-M by up to 102% and 48%, respectively. However, it had no effect on the cytoskeletal protein beta-tubulin. Hence, the quantity of synaptic membrane probably increased. The precursors act by enhancing the substrate saturation of enzymes that initiate their incorporation into phosphatidylcholine and phosphatidylethanolamine and by UTP-mediated activation of P2Y receptors. Alzheimer's disease brains contain fewer and smaller synapses and reduced levels of synaptic proteins, membrane phosphatides, choline and DHA. The three phosphatide precursors might thus be useful in treating this disease.
胆碱；嘧啶（如尿苷，通过UTP转化为脑CTP）；以及多不饱和脂肪酸（如二十二碳六烯酸）；磷脂酰乙醇胺可能利用其中两种，即嘧啶和多不饱和脂肪酸。我们观察到，摄入这些前体可显著提高沙鼠脑中膜磷脂和突触蛋白水平。（沙鼠而非大鼠的嘧啶代谢与人类相似。）动物每天通过灌胃接受含氯化胆碱和UMP（尿苷来源）和/或DHA的饮食，持续4周。单独使用尿苷和胆碱或单独使用DHA时，脑磷脂酰胆碱升高了13 - 22%，联合使用时升高了45%，磷脂酰乙醇胺和其他磷脂升高了39 - 74%。1 - 3周后升高幅度较小。联合使用还使囊泡蛋白突触素-1增加了41%，突触后蛋白PSD - 95增加了38%，神经突神经原纤维蛋白NF - 70和NF - M分别增加了高达102%和48%。然而，它对细胞骨架蛋白β-微管蛋白没有影响。因此，突触膜的数量可能增加了。这些前体通过增强启动它们掺入磷脂酰胆碱和磷脂酰乙醇胺的酶的底物饱和度以及通过UTP介导的P2Y受体激活来发挥作用。阿尔茨海默病患者的大脑中突触数量减少且体积变小，突触蛋白、膜磷脂、胆碱和DHA水平降低。因此，这三种磷脂前体可能对治疗这种疾病有用。
