TRANSBILAYER EFFECTS OF ALCOHOL ON BRAIN MEMBRANES

乙醇和/或老化对细胞膜影响的研究 流动性和组成已经报告了散体的变化 薄膜。然而，膜由两个单分子层组成 或看起来不成对且在结构上 在成分上不对称。关于乙醇诱导的数据 变化和随年龄的变化是这两者的平均值 传单。使用一种新的方法来确定膜结构域， 我们最近发现，突触血浆的外叶 与内叶相比，膜(SPM)的流动性更强 乙醇在体外对外叶的影响更大。 乙醇的这种不对称效应可能是必要的 跨膜功能对乙醇的响应，例如酶 活动、运输、受体复合体。这样的效果 可能不存在于老年动物的细胞膜中，因为 膜不对称性的年龄变化 随着年龄的增长，脂肪在两叶间的分布。 这一假说将通过生物物理和生化手段进行检验。 检查跨双层结构和 6月龄、18月龄和30月龄SPM的组成特性 C578BL/6NNIA小鼠。此应用程序中的实验将 解决以下问题：1)乙醇对人体健康有什么影响 体外(即流动性)和体内(即流动性、脂质分布) SPM的外叶和内叶；2)流动性和脂质 不对称性随年龄增长而变化，有年龄吗？ 乙醇体外和体内作用的差异 个别膜片？；3)乙醇的持续时间是多少？ 在停药时引起SPM传单的变化，是这个年龄- 相关？；以及4)膜不对称性的修改会改变吗 年龄差异对乙醇的反应。拟议的工作将 首次研究乙醇对外周和外周血液的影响 内膜小叶。我们的意图是， 拟议的研究将提供对以下影响的新见解 膜结构域上的乙醇，膜中年龄变化的数据 以及可能改变由以下因素引起的膜变化的程序 乙醇和衰老。

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.