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.
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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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