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Eur J Pharmacol. 2015 Dec 5;768:49-57. doi: 10.1016/j.ejphar.2015.10.026. Epub 2015 Oct 17.

Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice.

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Department of Histology and Embryology of Taishan Medical University, Taian, Shandong 271000, PR China.
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Department of Neurosurgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong Province 250012, PR China.
Department of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address:


Current evidence supports that depression is accompanied by the activation of the inflammatory-response system, and overproduction of pro-inflammatory cytokines may play a role in the pathophysiology of depressive disorders. Resveratrol has anti-inflammatory, antioxidant and anti-depressant-like properties. Using an animal model of depression induced by a single administration of lipopolysaccharide (LPS), the present study investigated the effects of resveratrol on LPS-induced depressive-like behavior and inflammatory-response in adult mice. Our results showed that pretreatment with resveratrol (80mg/kg, i.p.) for 7 consecutive days reversed LPS-increased the immobility time in the forced swimming test and tail suspension test, and LPS-reduced sucrose preference test. Moreover, the antidepressant action of resveratrol was paralleled by significantly reducing the expression levels of pro-inflammatory cytokines, and up-regulating phosphorylated cAMP response-element-binding protein (pCREB)/brain-derived neurotrophic factor (BDNF) expression in prefrontal cortex (PFC) and hippocampus. In addition, resveratrol ameliorated LPS-induced NF-κB activation in the PFC and hippocampus. The results demonstrate that resveratrol may be an effective therapeutic agent for LPS-induced depressive-like behavior, partially due to its anti-inflammatory aptitude and by modulating pCREB and BDNF expression in the brain region of mice.


Depression; Lipopolysaccharide; NF-κB; Pro-inflammatory cytokines; Resveratrol

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