کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5040597 1473902 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants
چکیده انگلیسی


- Inflammation and reduced neurogenesis are associated with the pathophysiology of depression.
- IL-1β decreased neurogenesis in human hippocampal progenitor cells.
- EPA, DHA, sertraline and venlafaxine prevented the IL-1β-induced reduction in neurogenesis.
- EPA and DHA reversed the IL-1β-induced increase in kynurenine levels.
- EPA, DHA, sertraline and venlafaxine decreased the upregulation of IDO and KMO mRNA.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 65, October 2017, Pages 230-238
نویسندگان
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