Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD)
Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD)
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DOI：
10.1016/j.nbd.2007.06.007
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发表时间：
2007-10-01
影响因子：
6.1
通讯作者：
Kiliaan, A. J.
中科院分区：
文献类型：
--
作者：
Hooijmans, C. R.;Rutters, F.;Kiliaan, A. J.
高胆固醇饮食和低二十二碳六烯酸（DHA）摄入是阿尔茨海默病（AD）的危险因素。然而，目前还不清楚这些成分如何影响疾病的进程。我们研究了饮食脂质对18个月大的APP/PS1小鼠大脑中β淀粉样蛋白沉积和血液循环的影响。从6个月大开始，给小鼠喂食常规啮齿动物食物、含有1%胆固醇的典型西方饮食（TWD）或具有高（0.5%）水平DHA的饮食12个月。用H-2磁共振波谱和梯度回波增强MRI测定相对脑血容量（rCBV）和相对脑血流量（CBF）。用免疫组织化学在固定的脑组织中观察到P-淀粉样蛋白的沉积。TWD饮食增加了海马齿状回的斑块负荷，但没有显着降低rCBV。相比之下，富含DHA的饮食增加了rCBV，而没有改变血流，这表明可能由于血管舒张和血管P-淀粉样蛋白沉积量减少而导致大脑中的更大循环。总之，我们的研究结果表明，长期摄入膳食脂质可以影响脑循环和P-淀粉样蛋白沉积，并支持血流动力学变化参与AD的发展。(C)2007爱思唯尔公司All rights reserved.
High dietary cholesterol and low dietary docosahexaenoic acid (DHA) intake are risk factors for Alzheimer's disease (AD). However, it is unclear how these components influence the course of the disease. We investigated the effects of dietary lipids on beta-amyloid deposition and blood circulation in the brains of 18-month-old APP/PS1 mice. Starting at 6 months of age, mice were fed a regular rodent chow, a Typical Western Diet (TWD) containing 1% cholesterol, or a diet with a high (0.5%) level of DHA for 12 months. Relative cerebral blood volume (rCBV) and flow (CBF) were determined with H-2 MR spectroscopy and gradient echo contrast enhanced MRI. Deposition of P-amyloid was visualized in fixed brain tissue with immunohistochemistry. The TWD diet increased plaque burden in the dentate gyrus of the hippocampus, but did not significantly reduce rCBV. In contrast, the DHA-enriched diet increased rCBV without changing blood flow indicating a larger circulation in the brain probably due to vasodilatation and decreased the amount of vascular P-amyloid deposition. Together, our results indicate that the long-term intake of dietary lipids can impact both brain circulation and P-amyloid deposition, and support the involvement of hemodynamic changes in the development of AD. (C) 2007 Elsevier Inc. All rights reserved.