Lipid signaling in experimental epilepsy
Lipid signaling in experimental epilepsy
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DOI：
10.1007/s11064-005-6878-4
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Bazan, NG
中科院分区：
文献类型：
--
作者：
Cole-Edwards, KK;Bazan, NG
谷氨酸的释放激活了对学习和记忆至关重要的信号通路，而在癫痫发作过程中对这些通路的过度刺激会导致异常的突触可塑性，与过度兴奋和癫痫易发状态相关。癫痫发作导致突触膜脂衍生脂肪酸的快速积累，证据表明，这调节了适应不良的连接。在这里，我们概述了花生四烯基和肌醇衍生的信使前列腺素(PGs)和二酰甘油(DAG)在癫痫实验模型中的意义。我们利用自己实验室的研究来强调环氧合酶-2(COX-2)及其产物PGs的致痫作用，并讨论了PGs在细胞水平上调节膜兴奋性和突触传递的可能机制。最后，我们讨论了AA-DAG信号在突触可塑性和癫痫易感性中的作用，重点介绍了我们实验室最近对DAG激酶epsilon(DGK Epsilon)基因敲除小鼠的研究。
Glutamate release activates signaling pathways important for learning and memory, and over-stimulation of these pathways during seizures leads to aberrant synaptic plasticity associated with hyper-excitable, seizure-prone states. Seizures induce rapid accumulation of membrane lipid-derived fatty acids at the synapses which, evidence suggests, regulate maladaptive connectivity. Here we give an overview of the significance of the arachidonyl- and inositol-derived messengers, prostaglandins (PGs) and diacylglycerol (DAG), in experimental models of epilepsy. We use studies conducted in our own laboratory to highlight the pro-epileptogenic role of cyclooxygenase-2 (COX-2) and its products, the PGs, and we discuss the possible mechanisms by which PGs may regulate membrane excitability and synaptic transmission at the cellular level. We conclude with a discussion of AA-DAG signaling in synaptic plasticity and seizure susceptibility with an emphasis on recent studies in our laboratory involving DAG kinase epsilon (DGK epsilon)-knockout mice.