Ether Lipids In The Central Nervous System

(1)醚磷脂有助于突触膜内容物和重塑，并在过氧化物酶体和微粒体中合成。脑醚磷脂含量在人类过氧化物酶体障碍（例如Zellweger综合征）和突触功能障碍的阿尔茨海默病动物模型中受到干扰。一种新的体内动力学方法，使用氚标记的十六烷酸作为醚磷脂合成的前体，开发了图像和定量醚磷脂合成率在清醒的啮齿动物的大脑。灰质中的合成速率比以前发表的要快得多，半衰期不到一小时，与醚磷脂代谢在突触膜周转中的作用一致。因此，新的示踪剂方法可用于检查正常条件下的突触重塑和过氧化物酶体或突触疾病过程的动物模型。(3)在涉及过氧化物酶体受体的小鼠敲除模型（PPARbeta敲除小鼠）中，脑醚磷脂代谢和组成显示出缺陷。这些数据表明，PPARbeta参与维持成年雌性小鼠脑中的FA和磷脂水平，并提供了强有力的证据表明PPARbeta在脑过氧化物酶体酰基辅酶A利用中的作用。

(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.