title: Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex.
abstract: Depression is one of the most common neuropsychiatric disorders and has been associated with oxidative stress and brain protein alterations. Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities including potent antidepressant-like effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of resveratrol by measuring oxidative stress parameters and phosphorylation of AKT/mTOR pathway in the rat hippocampus and prefrontal cortex (PFC) exposed to the chronic unpredictable mild stress (CUMS). Male Wistar rats were subjected to CUMS protocol for a period of 4 weeks to induce depressive-like behavior. The results showed that resveratrol treatment (80 mg/kg/i.p. 4 weeks) significantly reversed the CUMS-induced behavioral abnormalities (reduced sucrose preference, increased immobility time and decreased locomotor activity) and biochemical changes (increased lipid peroxidation and decreased superoxide dismutase). Additionally, CUMS exposure significantly decreased phosphorylation of Akt and mTOR in the hippocampus and PFC, while resveratrol treatment normalized these parameters. In conclusion, our study showed that resveratrol exerted antidepressant-like effects in CUMS rats, which was mediated in part by its antioxidant action, up-regulation of phosphor-Akt and mTOR levels in the hippocampus and PFC.
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Song
authors.initials: S
authors.lastname: liu
authors.affiliation: 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 and Brain Science Research Institute, Shandong University, 107#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Medical Psychology Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Hansen
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department 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: Department of Medical Psychology Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Shishi
authors.initials: S
authors.lastname: Bo
authors.affiliation: Department of Medical Psychology Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Yunkai
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Physiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Psychology Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China. Electronic address: liudexiang@sdu.edu.cn.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000150:complications; D013550:Swimming / Q000523:psychology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D013267:Stilbenes; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D000077185:Resveratrol
keywords: Akt; Chronic unpredictable mild stress (CUMS); Depression; Resveratrol; mTOR