Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease.
Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease.
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在阿尔茨海默病转基因小鼠模型中，诱导硬脑膜淋巴管生成促进可溶性β-淀粉样蛋白从大脑中清除
DOI：
10.4103/1673-5374.230299
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发表时间：
2018-04
影响因子：
6.1
通讯作者：
Yao ZB
中科院分区：
文献类型：
--
作者：
Wen YR;Yang JH;Wang X;Yao ZB
淀粉样蛋白-β从脑中清除受损是阿尔茨海默病的核心病理事件。目前的药物治疗效果不理想，有些治疗方法会引起严重的副作用。脑膜淋巴管可能是β淀粉样蛋白清除的新途径。本研究旨在探讨促进硬脑膜淋巴管生成是否有助于β淀粉样蛋白从脑中的清除。首先，用100 ng/mL重组人血管内皮生长因子-C（rhVEGF-C）蛋白处理人淋巴管内皮细胞。光学显微镜证实，rhVEGF-C，血管内皮生长因子受体-3（VEGFR-3）的特异性配体，显着促进管形成的人淋巴管内皮细胞在体外。在体内研究中，将200 μg/mL rhVEGF-C注射到APP/PS1转基因小鼠的小脑延髓池中，每2天注射一次，共注射4次。免疫荧光染色显示阿尔茨海默病小鼠的硬脑膜淋巴管生成水平高。rhVEGF-C给药1周后，酶联免疫吸附试验结果显示脑脊液和脑中可溶性淀粉样蛋白-β水平降低。Morris水迷宫实验显示空间认知功能恢复。这些结果表明，硬膜淋巴管生成的上调促进淀粉样蛋白-β从APP/PS1小鼠的脑中清除，表明VEGF-C/VEGFR-3信号传导途径作为阿尔茨海默病的治疗靶点的潜力。
Impaired amyloid-β clearance from the brain is a core pathological event in Alzheimer's disease. The therapeutic effect of current pharmacotherapies is unsatisfactory, and some treatments cause severe side effects. The meningeal lymphatic vessels might be a new route for amyloid-β clearance. This study investigated whether promoting dural lymphangiogenesis facilitated the clearance of amyloid-β from the brain.First, human lymphatic endothelial cells were treated with 100 ng/mL recombinant human vascular endothelial growth factor-C (rhVEGF-C) protein. Light microscopy verified that rhVEGF-C, a specific ligand for vascular endothelial growth factor receptor-3 (VEGFR-3), significantly promoted tube formation of human lymphatic endothelial cells in vitro. In an in vivo study, 200 μg/mL rhVEGF-C was injected into the cisterna magna of APP/PS1 transgenic mice, once every 2 days, four times in total. Immunofluorescence staining demonstrated high levels of dural lymphangiogenesis in Alzheimer's disease mice. One week after rhVEGF-C administration, enzyme-linked immunosorbent assay results showed that levels of soluble amyloid-β were decreased in cerebrospinal fluid and brain. The Morris water maze test demonstrated that spatial cognition was restored. These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice, suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer's disease.
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影响因子：
20.3
作者：
Hirakawa, Satoshi;Brown, Lawrence F.;Detmar, Michael
通讯作者：
Detmar, Michael
影响因子：
4.8
作者：
Gupta A;Iadecola C
通讯作者：
Iadecola C
DOI：
10.3233/jad-160110
发表时间：
2016-04-12
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Hoscheidt SM;Starks EJ;Oh JM;Zetterberg H;Blennow K;Krause RA;Gleason CE;Puglielli L;Atwood CS;Carlsson CM;Asthana S;Johnson SC;Bendlin BB
通讯作者：
Bendlin BB
影响因子：
--
作者：
Bachmann, Bjoern O.;Bock, Felix;Cursiefen, Claus
通讯作者：
Cursiefen, Claus
影响因子：
6.5
作者：
Kajiya, Kentaro;Sawane, Mika;Detmar, Michael
通讯作者：
Detmar, Michael