Format

Send to

Choose Destination
Brain Behav Immun. 2017 Oct;65:230-238. doi: 10.1016/j.bbi.2017.05.006. Epub 2017 May 18.

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

Author information

1
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
2
Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
3
Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, College of Medicine, China Medical University, Taichung, Taiwan.
4
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; South London and Maudsley NHS Foundation Trust, Denmark Hill, Camberwell, London, UK.
5
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. Electronic address: patricia.zunszain@kcl.ac.uk.

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.

KEYWORDS:

Cytokines; Fish oil; IL-1 beta; Immune; Kynurenine-pathway; Neurogenic; PUFA; Sertraline; Venlafaxine

PMID:
28529072
PMCID:
PMC5540223
DOI:
10.1016/j.bbi.2017.05.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center