Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice.
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.
Department of Histology and Embryology of Taishan Medical University, Taian, Shandong 271000, PR China.
Li
L
Ge
Department of Histology and Embryology of Taishan Medical University, Taian, Shandong 271000, PR China.
Liwei
L
Liu
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Hansen
H
Liu
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Song
S
Liu
Department of Neurosurgery, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong Province 250012, PR China.
Hao
H
Xue
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Xueer
X
Wang
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Lin
L
Yuan
Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Zhen
Z
Wang
Department of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: liudexiang@sdu.edu.cn.
Dexiang
D
Liu
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D017397:Prefrontal Cortex / Q000473:pathology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D013395:Sucrose / Q000494:pharmacology
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013267:Stilbenes; D013395:Sucrose; D000242:Cyclic AMP; D000077185:Resveratrol
Depression; Lipopolysaccharide; NF-κB; Pro-inflammatory cytokines; Resveratrol