Ether Lipids In The Central Nervous System

(1)乙醚磷脂有助于突触膜的含量和重塑，并在过氧化物体和微粒体中合成。在人类过氧酶体疾病(如Zellweger综合征)和阿尔茨海默病突触功能障碍动物模型中，脑乙醚磷脂含量受到干扰。利用氚标记的十六酸作为乙醚磷脂合成的前体，建立了一种新的体内动力学方法，用于成像和定量清醒啮齿动物脑中的乙醚磷脂合成速率。灰质的合成速度比以前发表的要快得多，半衰期不到一小时，与乙醚磷脂代谢在突触膜翻转中的作用一致。因此，这种新的示踪剂方法可以用来检查正常条件下的突触重构，以及在过氧酶体或突触疾病过程的动物模型中。(3)在含有PPARbeta基因敲除小鼠的PPARbeta基因敲除小鼠模型中，脑乙醚磷脂代谢和组成存在缺陷。这些数据表明，PPARbeta参与维持成年雌性小鼠脑内FA和磷脂的水平，并提供了强有力的证据，表明PPARbeta在大脑对过氧化体酰辅酶A的利用中发挥了作用。

(1) Ether phospholipids contribute to synaptic membrane content and remodeling, and are synthesized in peroxisomes and microsomes. Brain ether phospholipid content is disturbed in human peroxisomal disorders (e.g. Zellweger's syndrome) and in Alzheimer disease animal models of synaptic dysfunction.. A new in vivo kinetic method, using tritium-labeled hexadecanoic acid as a precursor for ether phospholipids synthesis, was developed to image and quantify ether phospholipid synthesis rates in brains of awake rodents. Synthesis rates in gray matter were shown to be much more rapid than previously published, with half-lives of less than an hour, and consistent with the role of ether phospholipid metabolism in synaptic membrane turnover. Thus, the new tracer method can be used to examine synaptic remodeling under normal conditions and in animal models of peroxisomal or synaptic disease processes. (3) Brain ether phospholipid metabolism and composition were shown to be defective in a mouse knockout model involving peroxisomal receptor, the PPARbeta knockout mouse. The data suggest that PPARbeta is involved in maintaining FA and phospholipid levels in adult female mouse brain and provide strong evidence that suggests a role for PPARbeta in brain peroxisomal acyl-CoA utilization.