The Emerging Role of the Double-Edged Impact of Arachidonic Acid- Derived Eicosanoids in the Neuroinflammatory Background of Depression.

Author(s): Magdalena Regulska, Magdalena Szuster-Głuszczak, Ewa Trojan, Monika Leśkiewicz, Agnieszka Basta-Kaim*

Journal Name: Current Neuropharmacology

Volume 19 , Issue 2 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


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.

Keywords: Arachidonic acid, eicosanoids, neuroinflammation, prostaglandins, lipoxins, resolution of inflammation, depression.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 07 August, 2020
Page: [278 - 293]
Pages: 16
DOI: 10.2174/1570159X18666200807144530
Price: $65

Article Metrics

PDF: 27