The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat.
The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat.
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DOI：
10.3233/jad-2010-091414
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Davidson TL
中科院分区：
文献类型：
--
作者：
Kanoski SE;Zhang Y;Zheng W;Davidson TL
认知障碍和阿尔茨海默病与摄入以高水平饱和脂肪和简单碳水化合物为特征的西方饮食有关。在大鼠中，这些饮食成分已被证明会破坏海马依赖的学习和记忆过程，特别是那些涉及空间记忆的过程。利用大鼠模型，本研究评估了高能量（HE）饮食的消耗程度，类似于现代西方文化中发现的，对海马功能产生选择性损伤，而不是更全面的认知破坏。在90天内，研究人员对三种非空间辨别学习问题的学习和记忆表现进行了检查，这些问题对海马体完整性的依赖程度不同。结果表明，相对于食材喂养的对照组，食用高糖饮食会损害小鼠在海马依赖特征负辨别问题上的表现，而在不依赖海马的两个辨别问题上则不会受到影响。为了探讨食用高糖饮食损害认知功能的机制，我们研究了高糖饮食对血脑屏障完整性的影响。我们发现he饮食消耗导致脉络膜丛和血脑屏障中紧密连接蛋白mRNA表达减少，特别是Claudin-5和-12。因此，在he饮食后，在海马中观察到荧光素钠的血脑通透性增加，而在纹状体和前额叶皮层中则没有。这些结果表明，海马功能可能特别容易受到he饮食的破坏，这种破坏可能与血脑屏障完整性受损有关。
Cognitive impairment and Alzheimer’s Disease are linked with intake of a Western Diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selective impairment in hippocampal function as opposed to a more global cognitive disruption. Learning and memory performance was examined following 90-days consumption of an HE-diet in three nonspatial discrimination learning problems that differed with respect to their dependence on the integrity of the hippocampus. The results showed that consumption of the HE-diet impaired performance in a hippocampal-dependent feature negative discrimination problem relative to chow-fed controls, whereas performance was spared on two discrimination problems that do not rely on the hippocampus. To explore the mechanism whereby consuming HE-diets impairs cognitive function, we investigated the effect of HE-diets on the integrity of the blood-brain barrier (BBB). We found that HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin-5 and -12, in the choroid plexus and the BBB. Consequently, an increased blood-to-brain permeability of sodium fluorescein was observed in the hippocampus, but not in the striatum and prefrontal cortex following HE-diet access. There results indicate that hippocampal function may be particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity.