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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Main Authors: Ya-Ru Wen, Jun-Hua Yang, Xiao Wang, Zhi-Bin Yao
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2018-01-01
Series:Neural Regeneration Research
Subjects:
Online Access: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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spelling 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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