Immunoendocrinology Laboratory, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343 Krakow, Poland.
Curr Neuropharmacol. 2021;19(2):278-293. doi: 10.2174/1570159X18666200807144530.
Eicosanoids are arachidonic acid (AA) derivatives belonging to a family of lipid signalling mediators that are engaged in both physiological and pathological processes in the brain. Recently, their implication in the prolonged inflammatory response has become a focus of particular interest because, in contrast to acute inflammation, chronic inflammatory processes within the central nervous system (CNS) are crucial for the development of brain pathologies including depression. The synthesis of eicosanoids is catalysed primarily by cyclooxygenases (COX), which are involved in the production of pro-inflammatory AA metabolites, including prostaglandins and thromboxanes. Moreover, eicosanoid synthesis is catalysed by lipoxygenases (LOXs), which generate both leukotrienes and anti-inflammatory derivatives such as lipoxins. Thus, AA metabolites have double- edged pro-inflammatory and anti-inflammatory, pro-resolving properties, and an imbalance between these metabolites has been proposed as a contributor or even the basis for chronic neuroinflammatory effects. This review focuses on important evidence regarding eicosanoid-related pathways (with special emphasis on prostaglandins and lipoxins) that has added a new layer of complexity to the idea of targeting the double-edged AA-derivative pathways for therapeutic benefits in depression. We also sought to explore future research directions that can support a pro-resolving response to control the balance between eicosanoids and thus to reduce the chronic neuroinflammation that underlies at least a portion of depressive disorders.
类二十烷酸是花生四烯酸 (AA) 的衍生物，属于一类脂质信号介质家族，参与大脑的生理和病理过程。最近，它们在延长的炎症反应中的作用引起了特别的关注，因为与急性炎症不同，中枢神经系统 (CNS) 中的慢性炎症过程对于包括抑郁症在内的脑病理学的发展至关重要。类二十烷酸的合成主要由环加氧酶 (COX) 催化，COX 参与产生促炎的 AA 代谢物，包括前列腺素和血栓素。此外，类二十烷酸的合成还由脂加氧酶 (LOX) 催化，生成白三烯和抗炎衍生物，如脂氧素。因此，AA 代谢物具有双重促炎和抗炎、促解决的特性，这些代谢物之间的失衡被认为是慢性神经炎症效应的原因之一，甚至是其基础。本综述重点介绍了与类二十烷酸相关的途径的重要证据（特别强调前列腺素和脂氧素），这为针对具有双重作用的 AA 衍生物途径以获得治疗抑郁症的益处的想法增添了新的复杂性。我们还试图探索未来的研究方向，以支持促解决反应，从而控制类二十烷酸之间的平衡，从而减少至少部分抑郁症所基于的慢性神经炎症。
