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

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Alessandra Borsini, Silvia Alboni, Luis M Tojo, Mark A. Horowitz, Kuan-Pin Su, Giuseppe Cannazza, Carmine Maria Pariante, Patricia Ana Zunszain

Original languageEnglish
Pages (from-to)230-238
JournalBrain, Behavior, and Immunity
Volume65
Early online date18 May 2017
DOIs
Accepted/In press8 May 2017
E-pub ahead of print18 May 2017
PublishedOct 2017

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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) β 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 (ω-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-1β (10 ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1 µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1 µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10 µM) or docosahexaenoic acid (DHA, 10 µM). Co-incubation with each of these compounds reversed the IL-1β-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1β-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1β-induced increase in quinolinic acid and mRNA levels of kynurenine 3-monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and ω-3 fatty acids on the reduction of neurogenesis caused by IL-1β, 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.

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