High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model.
High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model.
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DOI：
10.1111/acel.12818
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发表时间：
2018-10
期刊：
影响因子：
7.8
通讯作者：
Cooper I
中科院分区：
文献类型：
--
作者：
Elhaik Goldman S;Goez D;Last D;Naor S;Liraz Zaltsman S;Sharvit-Ginon I;Atrakchi-Baranes D;Shemesh C;Twitto-Greenberg R;Tsach S;Lotan R;Leikin-Frenkel A;Shish A;Mardor Y;Schnaider Beeri M;Cooper I
2型糖尿病（T2 D）与阿尔茨海默病（AD）的风险增加有关。有证据表明，这两种疾病中的血脑屏障（BBB）受损，但其在两者之间的相互作用中的作用尚不清楚。在这里，我们研究了T2 D模型高脂饮食（HFD）对AD Tg 2576小鼠模型BBB功能的影响。我们发现HFD小鼠具有更高的体重、更多的胰岛素抵抗和更高的血清HDL胆固醇水平，主要是在Tg 2576小鼠中，其也具有更高的脑脂质含量。在行为方面，Tg 2576 HFD小鼠不太活跃，更焦虑，但在Morris水迷宫中的学习能力比常规饮食的Tg 2576更好。HFD对TG 2576小鼠皮质淀粉样蛋白β 1-42水平无影响，但增加海马胰岛素受体的转录水平。与Tg 2576 HFD小鼠相比，常规饮食的Tg 2576小鼠在8个月和12个月时表现出更多的BBB破坏，伴有更大的侧脑室体积，Tg 2576 HFD小鼠的BBB渗漏和脑室体积与野生型（WT）小鼠相似。我们的研究结果表明，在AD中，HFD可能通过改善BBB功能和脑萎缩而不是淀粉样蛋白β水平来促进更好的认知功能。CNS和外周组织中的脂质代谢和脑胰岛素信号传导可能是这种保护的基础。
Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood–brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high‐fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function. We showed that HFD mice had higher weight, more insulin resistance, and higher serum HDL cholesterol levels, primarily in Tg2576 mice, which also had higher brain lipids content. In terms of behavior, Tg2576 HFD mice were less active and more anxious, but had better learning in the Morris Water Maze compared to Tg2576 on regular diet. HFD had no effect on the level of amyloid beta 1–42 in the cortex of Tg2576 mice, but increased the transcription level of insulin receptor in the hippocampus. Tg2576 mice on regular diet demonstrated more BBB disruption at 8 and 12 months accompanied by larger lateral ventricles volume in contrast to Tg2576 HFD mice, whose BBB leakage and ventricular volume were similar to wild‐type (WT) mice. Our results suggest that in AD, HFD may promote better cognitive function through improvements of BBB function and of brain atrophy but not of amyloid beta levels. Lipid metabolism in the CNS and peripheral tissues and brain insulin signaling may underlie this protection.
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影响因子：
6.1
作者：
Kalaria RN
通讯作者：
Kalaria RN
影响因子：
5.2
作者：
Blázquez E;Velázquez E;Hurtado-Carneiro V;Ruiz-Albusac JM
通讯作者：
Ruiz-Albusac JM
影响因子：
6.5
作者：
Fellows, Kelly;Uher, Tomas;Ramanathan, Murali
通讯作者：
Ramanathan, Murali
影响因子：
--
作者：
Luchsinger, Jose A.;Reitz, Christiane;Mayeux, Richard
通讯作者：
Mayeux, Richard
影响因子：
38.1
作者：
Frisoni, Giovanni B.;Fox, Nick C.;Jack, Clifford R., Jr.;Scheltens, Philip;Thompson, Paul M.
通讯作者：
Thompson, Paul M.