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.

Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants / Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark A.; Tojo, Luis M.; Cannazza, Giuseppe; Su, Kuan-Pin; Pariante, Carmine M.; Zunszain, Patricia A.. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 65(2017), pp. 230-238.

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