Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats.
Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats.
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DOI：
10.1016/j.bbr.2016.06.012
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发表时间：
2016-10-01
影响因子：
2.7
通讯作者：
Freeman LR
中科院分区：
文献类型：
--
作者：
Ledreux A;Wang X;Schultzberg M;Granholm AC;Freeman LR
高脂肪饮食对认知能力有不利影响，并会增加大脑中的氧化应激和炎症。老化的大脑提供了一个脆弱的环境，高脂肪饮食可能会造成更多的损害。我们研究了高脂肪/高胆固醇（HFHC）饮食对年轻（4个月大）与老年（14个月大）雄性大鼠海马中认知能力、神经炎症标志物和磷酸化Tau（p-Tau）病理标志物的影响。年轻和老年雄性Fisher 344大鼠喂食HFHC饮食或正常对照饮食6个月。所有动物在水径向臂迷宫中进行认知测试12天，以评估空间和工作参考记忆。通过免疫组织化学分析海马组织的结构变化和炎症，以及Western印迹分析。喂食HFHC饮食的年轻和老年大鼠在空间工作记忆任务上表现出更差的表现。它们还表现出NeuN和钙结合蛋白-D28 k免疫反应性的显著降低以及海马结构中小胶质细胞的活化增加。海马的蛋白质印迹分析显示老年HFHC大鼠中p-Tau S202/T205和T231的水平更高，表明HFHC饮食暴露后Tau蛋白的异常磷酸化。这项工作证明了HFHC饮食诱导的认知障碍与衰老以及高脂肪饮食消费和阿尔茨海默病病理标志物之间的联系。
High fat diets have detrimental effects on cognitive performance, and can increase oxidative stress and inflammation in the brain. The aging brain provides a vulnerable environment to which a high fat diet could cause more damage. We investigated the effects of a high fat/high cholesterol (HFHC) diet on cognitive performance, neuroinflammation markers, and phosphorylated Tau (p-Tau) pathological markers in the hippocampus of Young (4-month old) versus Aged (14-month old) male rats. Young and Aged male Fisher 344 rats were fed a HFHC diet or a normal control diet for 6 months. All animals underwent cognitive testing for 12 days in a water radial arm maze to assess spatial and working reference memory. Hippocampal tissue was analyzed by immunohistochemistry for structural changes and inflammation, and Western blot analysis. Young and Aged rats fed the HFHC diet exhibited worse performance on a spatial working memory task. They also exhibited significant reduction of NeuN and calbindin-D28k immunoreactivity as well as an increased activation of microglial cells in the hippocampal formation. Western blot analysis of the hippocampus showed higher levels of p-Tau S202/T205 and T231 in Aged HFHC rats, suggesting abnormal phosphorylation of Tau protein following the HFHC diet exposure. This work demonstrates HFHC diet-induced cognitive impairment with aging and a link between high fat diet consumption and pathological markers of Alzheimer’s disease.
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影响因子：
6.3
作者：
Calvo-Ochoa, Erika;Hernandez-Ortega, Karina;Arias, Clorinda
通讯作者：
Arias, Clorinda
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通讯作者：
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通讯作者：
Heck, Sarah E.
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作者：
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通讯作者：
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影响因子：
4.8
作者：
Fifre, A;Sponne, I;Pillot, T
通讯作者：
Pillot, T