Lipid signaling: Sleep, synaptic plasticity, and neuroprotection
Lipid signaling: Sleep, synaptic plasticity, and neuroprotection
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DOI：
10.1016/j.prostaglandins.2005.07.001
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发表时间：
2005-09-01
影响因子：
2.9
通讯作者：
Bazan, NG
中科院分区：
文献类型：
--
作者：
Chen, C;Bazan, NG
越来越多的证据表明，生物活性脂质参与了突触功能和功能障碍的调节。我们已经证明，由血小板活化因子（PAF）和环氧合酶（考克斯）-2合成的PGE（2）介导的信号传导参与突触可塑性、记忆和神经元保护[Clark GD，Happel LT，Zorumski CF，Bazan NG.血小板活化因子对海马兴奋性突触传递的增强作用。Neuron 1992; 9：1211; Kato K，Clark GD，Bazan NG，Zorumski CF.血小板活化因子作为海马CA 1区长时程增强的潜在逆行信使。Nature 1994; 367：175; Izquierdo 1，Fin C，Schmitz PK，et al.通过海马内、杏仁核内或内嗅内输注血小板活化因子增强记忆，在抑制性回避中进行测量。Proc Natl Acad Sci USA 1995; 92：5047; Chen C，Magee CJ，Bazan NG.环氧合酶-2调节海马长时程突触可塑性中的前列腺素E2信号神经生理学杂志2002; 87：2851]。最近，我们发现长时间的连续觉醒（主要是快速眼动（REM）-睡眠剥夺，SD）导致海马长期突触可塑性和海马依赖性记忆形成的损害[McDermott CM，LaHoste GJ，Chen C，Musto A，Bazan NG，Magee JC.睡眠剥夺导致海马神经元的行为、突触和膜兴奋性改变。J Neurosci 2003; 23：9687]。为了探讨SD引起的损伤的机制，我们研究了SD后海马中的几种生物活性脂质。看来，SD导致前列腺素D-2（PGD（2））和2-花生四烯酸甘油（2-AG）增加，PGE（2）减少，表明这些脂质信使参与REM睡眠期间的记忆巩固。我们还探讨了内源性神经保护脂质的形成。为此，我们使用缺血再灌注损伤和基于LC-PDA-ESI-MS-MS的脂质组学分析，并确定了来自突触磷脂富集二十二碳六烯酸的二十二烷类化合物。一些二十二烷类化合物发挥有效的神经保护生物活性[Marcheselli VL，Hong S，Lukiw WJ，et a]。新型二十二烷类化合物抑制脑缺血再灌注介导的白细胞浸润和促炎基因表达。J Biol Chem 2003; 278：43807; Mukherjee PK，Marcheselli VL，Serhan CN，Bazan，NG.神经保护素D1：二十二碳六烯酸衍生的二十二碳三烯保护人类视网膜色素上皮细胞免受氧化应激。Proc Nat Acad Sci USA 2004; 101：8491）。总之，这些信号脂质参与突触可塑性，认知和生存的观察表明，脂质信号与几种功能（如学习和记忆，睡眠和实验性中风）和病理事件密切相关。药物滥用导致内源性信号脂质或其受体的改变，导致突触通路的改变，并对这些重要功能产生深远影响，本文就生物活性脂质在睡眠、突触传递和可塑性以及神经保护中的作用作一综述，重点介绍我们的实验研究，以及这些信号分子与功能的关系以及与某些神经系统疾病的关系。(c)2005年爱思唯尔公司All rights reserved.
increasing evidence indicates that bioactive lipids participate in the regulation of synaptic function and dysfunction. We have demonstrated that signaling mediated by platelet-activating factor (PAF) and cyclooxygenase (COX)-2-synthesized PGE(2) is involved in synaptic plasticity, memory, and neuronal protection [Clark GD, Happel LT, Zorumski CF, Bazan NG. Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron 1992; 9:1211; Kato K, Clark GD, Bazan NG, Zorumski CF. Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation. Nature 1994; 367:175; Izquierdo 1, Fin C, Schmitz PK, et al. Memory enhancement by intrahippocampal, intraamygdala or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance. Proc Natl Acad Sci USA 1995; 92:5047; Chen C, Magee CJ, Bazan NG. Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity. J Neurophysiol 2002; 87:2851]. Recently, we found that prolonged continuous wakefulness (primarily rapid eye movement (REM)-sleep deprivation, SD) causes impairments in hippocampal long-term synaptic plasticity and hippocampus-dependent memory formation [McDermott CM, LaHoste GJ, Chen C, Musto A, Bazan NG, Magee JC. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci 2003; 23:9687]. To explore the mechanisms underlying SD-induced impairments, we have studied several bioactive lipids in the hippocampus following SD. It appears that SD causes increases in prostaglandin D-2 (PGD(2)) and 2-arachidonylglycerol (2-AG), and a decrease in PGE(2), suggesting that these lipid messengers participate in memory consolidation during REM sleep. We have also explored the formation of endogenous neuroprotective lipids. Toward this aim, we have used ischemia-reperfusion damage and LC-PDA-ESI-MS-MS-based lipidomic analysis and identified docosanoids derived from synaptic phospholipid-enriched docosahexaenoic acid. Some of the docosanoids exert potent neuroprotective bioactivity [Marcheselli VL, Hong S, Lukiw WJ, et a]. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278:43807; Mukherjee PK, Marcheselli VL, Serhan CN, Bazan, NG. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Nat Acad Sci USA 2004; 101:8491). Taken together, these observations that signaling lipids participate in synaptic plasticity, cognition, and survival indicate that lipid signaling is closely associated with several functions (e.g; learning and memory, sleep, and experimental stroke) and pathologic events. Alterations in endogenous signaling lipids or their receptors resulting from drug abuse lead to changes in synaptic circuitry and induce profound effects on these important functions.In the present article, we will briefly review bioactive lipids involved in sleep, synaptic transmission and plasticity, and neuroprotection, focusing mainly on our experimental studies and how these signaling molecules are related to functions and implicated in some neurologic disorders. (c) 2005 Elsevier Inc. All rights reserved.