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Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants

Borsini, A; Alboni, S; Horowitz, MA; Tojo, LM; Cannazza, G; Su, K-P; Pariante, CM; (2017) Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants. Brain, Behavior, and Immunity , 65 pp. 230-238. 10.1016/j.bbi.2017.05.006. Green open access

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Abstract

Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) b, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (x-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway. We allowed neural cells to proliferate for 3 days and further differentiate for 7 days in the presence of IL-1b (10 ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1 mM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1 mM), or the x-3 fatty acids eicosapentaenoic acid (EPA, 10 mM) or docosahexaenoic acid (DHA, 10 mM). Co-incubation with each of these compounds reversed the IL-1b-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1b-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1b-induced increase in quinolinic acid and mRNA levels of kynurenine 3- monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and x-3 fatty acids on the reduction of neurogenesis caused by IL-1b, but acting through both common and different kynurenine pathway-related mechanisms. Further characterization of their individual properties will be of benefit towards improving a future personalized medicine approach.

Type: Article
Title: Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbi.2017.05.006
Publisher version: http://dx.doi.org/10.1016/j.bbi.2017.05.006
Language: English
Additional information: © 2017 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Fish oil, Cytokines, PUFA, Immune, IL-1 beta, Sertraline, Venlafaxine, Neurogenic, Kynurenine-pathway, ADULT HIPPOCAMPAL NEUROGENESIS, NEUROTOXIC KYNURENINE METABOLISM, MAJOR DEPRESSIVE DISORDER, QUINOLINIC ACID, INTERFERON-ALPHA, DOUBLE-BLIND, FISH-OIL, FATTY-ACIDS, MOUSE MODEL, INFLAMMATION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/10123681
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