title: Resveratrol prevents impaired cognition induced by chronic unpredictable mild stress in rats.
abstract: Depression is one of the most common neuropsychiatric disorders and has been associated with impaired cognition, as well as causing neuroendocrine systems and brain proteins alterations. Resveratrol is a natural polyphenol enriched in polygonum cuspidatum and has diverse biological activities, including potent antidepressant-like effects. The aim of this study was to determine whether resveratrol administration influences chronic unpredictable mild stress (CUMS)-induced cognitive deficits and explores underlying mechanisms. The results showed that CUMS (5weeks) was effective in producing cognitive deficits in rats as indicated by Morris water maze and novel object recognition task. Additionally, CUMS exposure significantly elevated serum corticosterone levels and decreased BDNF levels in the prefrontal cortex (PFC) and hippocampus, accompanied by decreased phosphorylation of extracellular signal-regulated kinase (pERK) and cAMP response element-binding protein (pCREB). Chronic administration of resveratrol (80mg/kg, i.p., 5weeks) significantly prevented all these CUMS-induced behavioral and biochemical alterations. In conclusion, our study shows that resveratrol may be an effective therapeutic agent for cognitive disturbances as was seen within the stress model and its neuroprotective effect was mediated in part by normalizing serum corticosterone levels, up-regulating of the BDNF, pCREB and pERK levels.
authors.affiliation: Institute of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gu
authors.affiliation: Institute of Bioscience, Luoyang Normal University, 71#, Longmen Road, Luoyang, Henan 471022, PR China; Institute of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Xueer
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xie
authors.affiliation: Institute of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Xian
authors.affiliation: Institute of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Medical Psychology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Institute of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: wangzhen@sdu.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003072:Cognition Disorders / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000517:prevention & control*; D003345:Corticosterone / Q000097:blood; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D013315:Stress, Psychological / Q000097:blood / Q000150:complications* / Q000188:drug therapy
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D018696:Neuroprotective Agents; D013267:Stilbenes; D048049:Extracellular Signal-Regulated MAP Kinases; D000077185:Resveratrol; D003345:Corticosterone
keywords: BDNF; Brain derived neurotrophic factor (BDNF); CREB; CUMS; Chronic unpredictable mild stress (CUMS); Cognitive deficits; ERK; HPA; MWM; Morris water maze; NORT; PFC; RT-PCR; Resveratrol; brain derived neurotrophic factor; cAMP response element-binding protein; chronic unpredictable mild stress; extracellular signal-regulated kinase; hypothalamic–pituitary–adrenal; novel object recognition task; prefrontal cortex; reverse transcription-polymerase chain reaction