Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease
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. Th...
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Wolters Kluwer Medknow Publications
2018-01-01
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doaj-183ff769e7fa4ed1acdf680c8a377a212020-11-25T03:44:26ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742018-01-0113470971610.4103/1673-5374.230299Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's diseaseYa-Ru WenJun-Hua YangXiao WangZhi-Bin YaoImpaired 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=4;spage=709;epage=716;aulast=Wennerve regeneration; dura mater; lymphangiogenesis; amyloid-β; Alzheimer′s disease; recombinant human vascular endothelial growth factor-C; lymphatic endothelial cells; lymphatic clearance; neural regeneration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ya-Ru Wen Jun-Hua Yang Xiao Wang Zhi-Bin Yao |
spellingShingle |
Ya-Ru Wen Jun-Hua Yang Xiao Wang Zhi-Bin Yao Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease Neural Regeneration Research nerve regeneration; dura mater; lymphangiogenesis; amyloid-β; Alzheimer′s disease; recombinant human vascular endothelial growth factor-C; lymphatic endothelial cells; lymphatic clearance; neural regeneration |
author_facet |
Ya-Ru Wen Jun-Hua Yang Xiao Wang Zhi-Bin Yao |
author_sort |
Ya-Ru Wen |
title |
Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease |
title_short |
Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease |
title_full |
Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease |
title_fullStr |
Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease |
title_full_unstemmed |
Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease |
title_sort |
induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of alzheimer's disease |
publisher |
Wolters Kluwer Medknow Publications |
series |
Neural Regeneration Research |
issn |
1673-5374 |
publishDate |
2018-01-01 |
description |
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. |
topic |
nerve regeneration; dura mater; lymphangiogenesis; amyloid-β; Alzheimer′s disease; recombinant human vascular endothelial growth factor-C; lymphatic endothelial cells; lymphatic clearance; neural regeneration |
url |
http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=4;spage=709;epage=716;aulast=Wen |
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