Resveratrol Attenuates Subacute Systemic Inflammation-Induced Spatial Memory Impairment via Inhibition of Astrocyte Activation and Enhancement of Synaptophysin Expression in the Hippocampus
Resveratrol Attenuates Subacute Systemic Inflammation-Induced Spatial Memory Impairment via Inhibition of Astrocyte Activation and Enhancement of Synaptophysin Expression in the Hippocampus
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白藜芦醇通过抑制星形胶质细胞活化和增强海马突触素表达来减轻亚急性全身炎症引起的空间记忆损伤
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发表时间：
2017
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通讯作者：
Lin-Lin Wang
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作者：
Ying-Ying Chen;Li Zhang;Dong-Ling Shi;Xing-Hui Song;Yue-Liang Shen;Ming-Zhi Zheng;Lin-Lin Wang
本研究的目的是探讨白藜芦醇对亚急性全身炎症诱导的小鼠认知记忆功能障碍的作用及其潜在机制。雄性 ICR 小鼠在水迷宫中接受四天的采集训练和一天的探索试验。采用腹腔注射脂多糖（LPS）（1 mg/kg）亚急性治疗5天，建立全身炎症模型。探针测试后处死所有小鼠，然后使用免疫组织化学或蛋白质印迹分析测定海马中胶质纤维酸性蛋白（GFAP）、突触素和sirtuin1（SIRT1）的表达。 Morris 水迷宫测试表明，LPS 治疗组的海马依赖性空间学习和记忆受损。白藜芦醇以剂量依赖性方式减轻 LPS 引起的记忆缺陷。免疫组织化学和蛋白质印迹分析显示，LPS 增加海马 GFAP 表达并抑制突触素表达，而白藜芦醇治疗可以阻止这种情况。 LPS 治疗降低了海马中 SIRT1 蛋白的表达，白藜芦醇可以预防这种情况。白藜芦醇的保护作用可以被特定的 SIRT1 抑制剂消除。我们的研究结果为白藜芦醇在亚急性全身炎症诱导的星形胶质细胞激活、突触改变和认知能力下降模型中对大脑的潜在治疗作用添加了新的实验数据。
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.