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Antidepressant-like effect of zileuton is accompanied by hippocampal neuroinflammation reduction and CREB/BDNF upregulation in lipopolysaccharide-challenged mice.
- Source :
-
Journal of Affective Disorders . Feb2018, Vol. 227, p672-680. 9p. - Publication Year :
- 2018
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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-κB p65, TNF-α, IL-1β, brain-derived neurotrophic factor (BDNF), and c-AMP response element-binding protein (CREB) were determined in the mouse hippocampus.<bold>Results: </bold>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-κB p65, TNF-α and IL-1β, and significantly increased the ratio of p-CREB/CREB or mBDNF/proBDNF in the hippocampus of the LPS-challenged mice.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANTIDEPRESSANTS
*LIPOXYGENASES
*BRAIN-derived neurotrophic factor
*THERAPEUTIC immobilization
*CREB protein
*ANIMAL behavior
*ANIMAL experimentation
*BIOCHEMISTRY
*BIOLOGICAL models
*CELLULAR signal transduction
*CYCLIC adenylic acid
*MENTAL depression
*FLUOXETINE
*HIPPOCAMPUS (Brain)
*INTERLEUKIN-1
*PHENOMENOLOGY
*MICE
*NERVE tissue proteins
*TUMOR necrosis factors
*HYDROXYUREA
*LIPOPOLYSACCHARIDES
*PHARMACODYNAMICS
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 01650327
- Volume :
- 227
- Database :
- Academic Search Index
- Journal :
- Journal of Affective Disorders
- Publication Type :
- Academic Journal
- Accession number :
- 127790896
- Full Text :
- https://doi.org/10.1016/j.jad.2017.11.047