Cerebrovascular Pathology in Hypertriglyceridemic APOB-100 Transgenic Mice.
Cerebrovascular Pathology in Hypertriglyceridemic APOB-100 Transgenic Mice.
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DOI：
10.3389/fncel.2018.00380
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发表时间：
2018
影响因子：
5.3
通讯作者：
Sántha M
中科院分区：
文献类型：
--
作者：
Hoyk Z;Tóth ME;Lénárt N;Nagy D;Dukay B;Csefová A;Zvara Á;Seprényi G;Kincses A;Walter FR;Veszelka S;Vígh J;Barabási B;Harazin A;Kittel Á;Puskás LG;Penke B;Vígh L;Deli MA;Sántha M
高胆固醇血症不仅是心血管疾病发展的一个严重危险因素，而且也与神经退行性疾病有关。在此之前，我们产生了过表达人类APOB-100蛋白的转基因小鼠，这是一种人类动脉粥样硬化的小鼠模型。在该模型中，我们观察到高血浆水平的甘油三酯、氧化应激、tau蛋白过度磷酸化、突触功能障碍、认知障碍、增加的神经细胞凋亡和神经变性。神经血管功能障碍被认为是神经退行性疾病发展的关键因素，但脑血管病理和神经退行性疾病之间的细胞和分子联系尚不完全清楚。我们的目的是研究APOB-100转基因小鼠的脑血管变化。我们描述了转基因动物慢性高胆固醇血症的发展动力学。APOB-100转基因小鼠海马区血脑屏障通透性增加，并伴有结构改变。透射电镜观察脑毛细血管内皮细胞紧密连接结构和星形胶质细胞端足水肿肿胀的变化。在从APOB-100转基因动物分离的脑微血管中，使用定量实时PCR测量Lox-1、Aqp 4增加，Meox-2、Mfsd 2a、Abcb 1a、Lrp 2、Glut-1、Nos 2、Nos 3、Vim减少，并且在转基因脑中Cdh 2和Gfap-σ基因表达减少。我们证实了减少P-糖蛋白（ABCB 1）和波形蛋白表达相关的神经血管单位的免疫染色在转基因脑切片，共聚焦显微镜。我们的结论是，在慢性高脂血症APOB-100转基因小鼠的功能和形态脑血管病变可以观察到，这种动物模型可能是一个有用的工具，研究脑血管病变和神经退行性变之间的联系。
Hypertriglyceridemia is not only a serious risk factor in the development of cardiovascular diseases, but it is linked to neurodegeneration, too. Previously, we generated transgenic mice overexpressing the human APOB-100 protein, a mouse model of human atherosclerosis. In this model we observed high plasma levels of triglycerides, oxidative stress, tau hyperphosphorylation, synaptic dysfunction, cognitive impairment, increased neural apoptosis and neurodegeneration. Neurovascular dysfunction is recognized as a key factor in the development of neurodegenerative diseases, but the cellular and molecular events linking cerebrovascular pathology and neurodegeneration are not fully understood. Our aim was to study cerebrovascular changes in APOB-100 transgenic mice. We described the kinetics of the development of chronic hypertriglyceridemia in the transgenic animals. Increased blood-brain barrier permeability was found in the hippocampus of APOB-100 transgenic mice which was accompanied by structural changes. Using transmission electron microscopy, we detected changes in the brain capillary endothelial tight junction structure and edematous swelling of astrocyte endfeet. In brain microvessels isolated from APOB-100 transgenic animals increased Lox-1, Aqp4, and decreased Meox-2, Mfsd2a, Abcb1a, Lrp2, Glut-1, Nos2, Nos3, Vim, and in transgenic brains reduced Cdh2 and Gfap-σ gene expressions were measured using quantitative real-time PCR. We confirmed the decreased P-glycoprotein (ABCB1) and vimentin expression related to the neurovascular unit by immunostaining in transgenic brain sections using confocal microscopy. We conclude that in chronic hypertriglyceridemic APOB-100 transgenic mice both functional and morphological cerebrovascular pathology can be observed, and this animal model could be a useful tool to study the link between cerebrovascular pathology and neurodegeneration.
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DOI：
10.1083/jcb.200207113
发表时间：
2003-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ehehalt R;Keller P;Haass C;Thiele C;Simons K
通讯作者：
Simons K
影响因子：
82.9
作者：
Deane, R;Yan, SD;Zlokovic, B
通讯作者：
Zlokovic, B
影响因子：
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作者：
Farkas, A. S.;Acsai, K.;Farkas, A.
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Farkas, A.
DOI：
10.1023/a:1011965307612
发表时间：
2001-01-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
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通讯作者：
Allt, G
影响因子：
3.7
作者：
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通讯作者：
Pizzuti A