Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain.

中文翻译：

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Omega-3脂肪酸在大脑中的抗炎作用：生理机制及其与药理学的关系

经典地，多不饱和脂肪酸（PUFA）被认为是大脑相对惰性的结构成分，对细胞膜的形成非常重要。在过去的10年中，已知有许多生物活性脂质介体酶促地从花生四烯酸（主要的n-6 PUFA）和二十二碳六烯酸（大脑中的主要n-3 PUFA）中衍生出来，可调节周围的免疫功能。在大脑中检测到并显示出调节小胶质细胞活化的作用。最近的进展集中在PUFA如何调节小胶质细胞的分子信号传导上，特别是在神经炎症和行为的背景下。几种活性药物调节脑脂质信号传导并提供针对脑部的概念证明。由于脑脂质代谢依赖于饮食，外周代谢，包括肝脏和血液，它们为大脑提供PUFA，而遗传基因，性别和衰老可能会改变它们。许多途径都可能被破坏，从而导致脑脂质稳态的改变。脑脂质信号传导途径在神经系统疾病中被改变，并且可能是开发新疗法的可行靶标。在这项研究中，我们特别讨论了n-3 PUFA及其代谢物如何调节小胶质细胞表型和功能，以发挥其在脑中的消炎和促溶活性。