Journal
JOURNAL OF AFFECTIVE DISORDERS
Volume 227, Issue -, Pages 672-680Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jad.2017.11.047
Keywords
5-lipoxygenase; Depression; Lipopolysaccharide; Neuroinflammation
Categories
Funding
- NSFC
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Background: Recent studies demonstrated beneficial effects of zileuton, a 5-lipoxygenase (5LO) inhibitor, on some brain diseases in animal models, but the role of zileuton in the depression remains unknown. Methods: We investigated the effects of zileuton on depressive behaviors using tail suspension test (TST), forced swimming test (FST) and novelty-suppressed feeding test (NSFT) in mice injected with lipopolysaccharide (LPS). The 5LO level, activation of microglia, NF-kappa B p65, TNF-alpha, IL-1 ss, brain-derived neurotrophic factor (BDNF), and c-AMP response element-binding protein (CREB) were determined in the mouse hippocampus. Results: We firstly found that the expression of hippocampal 5LO was gradually increased over LPS exposure and was reversed by fluoxetine administration. Zileuton significantly suppressed LPS-induced depressive behaviors, evidenced by the decreases in immobility time in TST and FST, as well as the latency to feed in NSFT. This treatment pronouncedly alleviated LPS-induced neuroinflammatory response, characterized by decreased 5LO, suppressed activation of microglia, decreased NF-kappa B p65, TNF-a and IL-1 ss, and significantly increased the ratio of p-CREB/CREB or mBDNF/proBDNF in the hippocampus of the LPS-challenged mice. Conclusions: Zileuton abrogates LPS-induced depressive-like behaviors and neuroinflammation, and enhances CREB/BDNF signaling in the hippocampus, suggesting that zileuton could have potential therapeutic value for depression.
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