Roles of multiple lipid mediators in stress and depression

International Immunology
Tomoyuki FuruyashikiShiho Kitaoka

Abstract

Prolonged or excessive stress may induce emotional and cognitive disturbances, and is a risk factor for mental illnesses. Using rodent chronic stress models of depression, roles of multiple lipid mediators related to inflammation have been revealed in chronic stress-induced emotional alterations. Prostaglandin (PG) E2, an arachidonic acid (AA)-derived lipid mediator, and its receptor subtype EP1 mediate depression-like behavior induced by repeated social defeat stress through attenuating prefrontal dopaminergic activity. Repeated social defeat stress activates microglia through innate immune receptors, and induces PGE2 synthesis through cyclooxygenase-1, a prostaglandin synthase enriched in microglia. PGD2, another AA-derived lipid mediator, has been implicated in depression induced by chronic stress, although either pro-depressive or anti-depressive actions have been reported. Chronic stress up-regulates hippocampal expression of 5-lipoxygenase, hence synthesis of cysteinyl leukotrienes, thereby inducing depression through their receptors. Consistent with beneficial effects of n-3 fatty acids in the diet of depressive patients, resolvins-a novel class of pro-resolving lipid mediators-in the brain attenuate neuroinflammation-as...Continue Reading

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Citations

Jun 30, 2019·Journal of Leukocyte Biology·Kehong ZhangXinchun Chen
Oct 15, 2019·Frontiers in Pharmacology·Corinne JoffreSophie Layé
Jul 29, 2020·International Journal of Molecular Sciences·Dariusz KotlegaMalgorzata Szczuko
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Sep 30, 2021·Molecular Brain·Aliza T EhrlichBrigitte L Kieffer

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