Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood-Brain Barrier Permeability and Neuroinflammation as Triggering Events.
Hippocampal Function Is Impaired by a Short-Term High-Fat Diet in Mice: Increased Blood-Brain Barrier Permeability and Neuroinflammation as Triggering Events.
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DOI：
10.3389/fnins.2021.734158
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发表时间：
2021
影响因子：
4.3
通讯作者：
de Bem AF
中科院分区：
文献类型：
--
作者：
de Paula GC;Brunetta HS;Engel DF;Gaspar JM;Velloso LA;Engblom D;de Oliveira J;de Bem AF
在世界范围内，特别是在西方文明中，大多数主食含有大量的脂肪和精制碳水化合物，导致越来越多的肥胖者。除了诱发代谢紊乱外，能量密集的食物摄入还被认为会损害大脑功能，如认知和情绪控制。在这里，我们证明了在高脂饮食（HFD）暴露开始后3天已经出现记忆功能受损，并且在悬尾试验中5天后出现抑郁样行为。这些变化之后，突触密度降低，线粒体功能的变化和星形胶质细胞激活海马。在行为改变之前或同时，我们发现海马中促炎细胞因子TNF-α和IL-6的诱导以及血脑屏障（BBB）通透性的增加。最后，在用TNF-α抑制剂处理的小鼠中，由HFD喂养引起的行为和BBB改变得到缓解，表明炎症信号传导对这些变化至关重要。总之，我们的研究结果表明，HFD快速触发与BBB破坏和神经炎症相关的海马功能障碍，促进突触和代谢功能的进行性破坏。除了阐明饮食和认知功能之间的联系外，我们的结果可能与理解神经退行性过程有关。一个说明性的方案总结了瑞士小鼠喂食高脂饮食（HFD）的主要结果，以及海马变化发生的确切时间。HFD 2天后检测到促炎细胞因子表达增加以及血脑屏障通透性增加。即使在饮食干预的第一周，也分别在第3、5和7天观察到记忆和学习障碍、抑郁样行为和突触变化。随后的海马改变（HFD消耗4周后）包括线粒体功能障碍和星形胶质细胞活化。
Worldwide, and especially in Western civilizations, most of the staple diets contain high amounts of fat and refined carbohydrates, leading to an increasing number of obese individuals. In addition to inducing metabolic disorders, energy dense food intake has been suggested to impair brain functions such as cognition and mood control. Here we demonstrate an impaired memory function already 3 days after the start of a high-fat diet (HFD) exposure, and depressive-like behavior, in the tail suspension test, after 5 days. These changes were followed by reduced synaptic density, changes in mitochondrial function and astrocyte activation in the hippocampus. Preceding or coinciding with the behavioral changes, we found an induction of the proinflammatory cytokines TNF-α and IL-6 and an increased permeability of the blood–brain barrier (BBB), in the hippocampus. Finally, in mice treated with a TNF-α inhibitor, the behavioral and BBB alterations caused by HFD-feeding were mitigated suggesting that inflammatory signaling was critical for the changes. In summary, our findings suggest that HFD rapidly triggers hippocampal dysfunction associated with BBB disruption and neuroinflammation, promoting a progressive breakdown of synaptic and metabolic function. In addition to elucidating the link between diet and cognitive function, our results might be relevant for the comprehension of the neurodegenerative process. An illustrative scheme summarizing the main outcomes in Swiss mice fed high-fat diet (HFD), with their exact time of onset of changes in the hippocampus. An increase in the expression of proinflammatory cytokines, together with the permeability of the blood–brain barrier was detected after 2 days of HFD. Even in the first week of dietary intervention, memory and learning impairment, depressive-like behavior, and synaptic changes were observed at 3, 5, and 7 days, respectively. Later hippocampal alterations (after 4 weeks of HFD consumption) include mitochondrial dysfunction and astrocytic activation.
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影响因子：
3.3
作者：
Davidson, T. L.;Hargrave, S. L.;Swithers, S. E.;Sample, C. H.;Fu, X.;Kinzig, K. P.;Zheng, W.
通讯作者：
Zheng, W.
影响因子：
1.9
作者：
Francis, Heather M.;Stevenson, Richard J.
通讯作者：
Stevenson, Richard J.
影响因子：
3.6
作者：
De Paula, Gabriela Cristina;de Oliveira, Jade;de Bem, Andreza Fabro
通讯作者：
de Bem, Andreza Fabro
影响因子：
64.5
作者：
Dietrich MO;Liu ZW;Horvath TL
通讯作者：
Horvath TL
DOI：
10.1016/j.bbi.2015.08.023
发表时间：
2016-01
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Hao S;Dey A;Yu X;Stranahan AM
通讯作者：
Stranahan AM