TRANSBILAYER EFFECTS OF ALCOHOL AND AGING ON BRAIN

检查乙醇和/或老化对膜影响的研究 流动性和组成的变化报告了散装 膜的 然而，膜由两个单层组成 或看起来不耦合并且在结构上 而且成分不对称 乙醇诱导的数据 随着年龄的变化和变化， 瓣叶 使用一种新的方法来确定膜结构域， 我们最近发现突触浆的外叶 与内瓣叶相比， 体外乙醇对外叶的影响更大。 乙醇的这种不对称效应可能是必要的， 响应乙醇的跨膜功能，例如，酶 活性、转运、受体效应复合物。 这样的效果 可能不存在于老年动物的膜中， 年龄变化导致的膜不对称性的变化 随着年龄的增长，两个小叶之间的脂质分布。 这一假设将使用生物物理和生物化学测试 检查跨双层结构和 6、18和30个月龄SPM的组成特性 C578 BL/6 NNIA小鼠。 本应用中的实验将 解决以下问题：1）乙醇在 体外（即，流动性）和体内（即，流动性，脂质分布） SPM？的内外小叶; 2)流动性和脂质 不对称性随年龄的增长而变化， 体外和体内乙醇对 单个膜小叶？3)乙醇的持续时间- 在停药后引起SPM瓣叶的变化，这个年龄- 有关系吗？和4）膜不对称性的改变是否会改变 年龄差异对乙醇的反应。 拟议的工作将 第一次检查乙醇对外部和外部环境的影响， 内膜小叶。 我们的意图是， 拟议的研究将提供新的见解， 乙醇对膜结构域的影响，关于膜老化变化的数据 以及可能改变细胞膜变化的程序， 乙醇和老化。

Studies examining effects of ethanol and/or aging on membrane fluidity and composition have reported on changes in the bulk membrane. However, the membrane consists of two monolayers or leaflets that do not appear to be coupled and are structurally and compositionally asymmetric. Data on ethanol-induced changes and changes with age have been an average of the two leaflets. Using a new method to determine membrane domains, we have recently found that the outer leaflet of synaptic plasma membranes (SPM) is more fluid as compared to the inner leaflet and that ethanol in vitro had a greater effect on the outer leaflet. This asymmetric effect of ethanol may be necessary for transmembrane function in response to ethanol, e.g., enzyme activity, transport, receptoreffector complex. Such an effect may not be present in membranes of aged animals as a result of age changes in membrane asymmetry resulting from changes in lipid distribution between the two leaflets with increasing age. This hypothesis will be tested using biophysical and biochemical procedures to examine the transbilayer structural and compositional properties of SPM from 6, 18, and 30 month old C578BL/6NNIA mice. The experiments in this application will address the following issues: 1) What are the effects of ethanol in vitro (i.e., fluidity) and in vivo (i.e., fluidity, lipid distribution) on the outer and inner leaflets of SPM?; 2) Does fluidity and lipid asymmetry change with increasing age and are there age differences in effects of ethanol in vitro and in vivo on the individual membrane leaflets?; 3) What is the duration of ethanol- induced changes in SPM leaflets upon withdrawal and is this age- related?; and 4) Will modification of membrane asymmetry alter age differences in response to ethanol. The proposed work will examine for the first time the effects of ethanol on the outer and inner membrane leaflets. It is our intention that the results of the proposed studies will provide new insight into effects of ethanol on membrane domains, data on age changes in membranes and procedures that might alter changes in membranes induced by ethanol and aging.