title: Resveratrol Attenuates Subacute Systemic Inflammation-Induced Spatial Memory Impairment via Inhibition of Astrocyte Activation and Enhancement of Synaptophysin Expression in the Hippocampus.
abstract: The aim of this study was to investigate the role of resveratrol on subacute systemic inflammation-induced dysfunction of cognitive memory in mice and its underlying mechanism. Male ICR mice were trained in a water maze for four days of acquisition training and one day of probe trial. Subacute treatment with lipopolysaccharide (LPS) (1 mg/kg) by intraperitoneal injection for 5 days was used to establish a systemic inflammatory model. All mice were sacrificed after probe testing, then the expression of glial fibrillary acidic protein (GFAP), synaptophysin, and sirtuin1 (SIRT1) in hippocampi were determined using immunohistochemistry or western blot analysis. Morris water maze tests indicated that hippocampus-dependent spatial learning and memory were impaired in LPS-treated group. Resveratrol attenuated LPS-induced memory deficit in dose-dependent manner. Immunohistochemistry and western blot analysis revealed that LPS increased hippocampal GFAP expression and inhibited synaptophysin expression, which were prevented by resveratrol treatment. Treatment with LPS declined the SIRT1 protein expression in the hippocampus, which could be prevented by resveratrol. The protective effect of resveratrol could be abolished by a specific SIRT1 inhibitor. Our findings add new experimental data for potential therapeutic effects of resveratrol in the brain in a model of subacute systemic inflammation-induced astrocyte activation, synaptic alteration and cognitive decline.
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Stem Cell and Tissue Engineering, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Shi
authors.affiliation: Core Facilities, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xing-Hui
authors.initials: XH
authors.lastname: Song
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yue-Liang
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, Zhejiang Medical College, Hangzhou, China zmzjjpdd181@sina.com.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zheng
authors.affiliation: Center for Stem Cell and Tissue Engineering, Zhejiang University School of Medicine, Hangzhou, China wanglinlin@zju.edu.cn.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Wang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D016708:Synaptophysin / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D013267:Stilbenes; D016708:Synaptophysin; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Learning and memory; astrocyte; lipopolysaccharides; sirtuin1; synaptophysin