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 3days and further differentiate for 7days in the presence of IL-1β (10ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10µM) or docosahexaenoic acid (DHA, 10µM). 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.
Highlights
Hippocampal neurogenesis has been widely associated with depression: reduced levels have been reported in depressed patients as well as in animal models of depression (Boldrini et al, 2009; Kempermann et al, 2008), and increasing its levels appears sufficient to reduce depressive-like behaviours (Hill et al, 2015)
The SSRI sertraline and the SNRI venlafaxine, as well as the two principal x-3 polyunsaturated fatty acids components of fish oils, eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), which have been associated with the pathogenesis and treatment of depression (Su et al, 2014; Su, 2012, 2009; Lin et al, 2012, 2010; Lu et al, 2010)
To establish whether the x-3 fatty acids EPA and DHA, and the monoaminergic antidepressants venlafaxine and sertraline, were able to reverse these detrimental effects of IL-1b cells were co-incubated with the cytokine and each of the compounds at doses previously established (Horowitz et al, 2015)
Summary
Hippocampal neurogenesis has been widely associated with depression: reduced levels have been reported in depressed patients as well as in animal models of depression (Boldrini et al, 2009; Kempermann et al, 2008), and increasing its levels appears sufficient to reduce depressive-like behaviours (Hill et al, 2015). Several factors can regulate neurogenesis: it can be stimulated by antidepressant drugs (Warner-Schmidt and Duman, 2006; Sahay and Hen, 2007; Malberg and Blendy, 2005) and negatively affected by pro-inflammatory cytokines such as interleukin-1 (IL-1) b (Goshen et al, 2008; Koo and Duman, 2008; Kuzumaki et al, 2010). This cytokine is of importance, as increased levels have been shown in peripheral blood and cere-.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
