LIPIDS AND SIGNAL TRANSDUCTION IN NEURONS

该计划项目有一个中心主题--血脂的作用，特别是 二十烷类化合物，作为神经递质，细胞内第二信使和 突触可塑性的调节剂。我们已经通过之前的 生化和电生理方面的工作和初步研究 支持这些脂质在神经信号中的作用的证据。在 过程中，我们发现了新的神经脂质代谢途径和 代谢物8(R)-脂氧合酶和8-酮被鉴定为“不寻常的”尼古丁 与前列腺素序列相似的乙酰胆碱受体 受体，并发现脂代谢和 哺乳动物海马区LTP和LTD模型的突触可塑性 以及二十烷类化合物生物化学、神经生理学和 分子生物学。这些方法结合在一起解决了三个主要问题 努力： 1)脂质调节剂在长期突触可塑性中的作用是什么？ 2)脂代谢产物在突触前易化中的作用是什么？ 尼古丁? 3)二十烷类信息素是哺乳动物的信息素吗？ 这些单位由来自5个独立实验室的调查人员组成。 并由一个致力于脂质生物化学的核心单位提供支持。

This Program Project has a central theme-the role of lipids, particularly eicosanoids, as neurotransmitters, intracellular second messengers and modulators of synaptic plasticity. We have identified through previous work and preliminary studies both biochemical and electrophysiological evidence that supports a role for these lipids in neural signaling. In the process, we have identified new neural lipid metabolic pathways and metabolites, 8(R)-lipoxygenase and 8-KETE, identified "unusual" nicotine acetylcholine receptors with sequence similarity to prostaglandin receptors, and identified strong links between lipid metabolism and synaptic plasticity in models of LTP and LTD in the mammalian hippocampus and in components in eicosanoid biochemistry, neural physiology and molecular biology. These methods are combined to address three major efforts: 1) What is the role of lipid modulators in long-term synaptic plasticity? 2) What is the role of lipid metabolites in presynaptic facilitation by nicotine? 3) Are eicosanoids pheromones in mammals? These Units are composed of investigators from 5 independent laboratories and are supported by a Core Unit devoted to lipid biochemistry.