Open AccessInduced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease
Author(s) -
Yaru Wen,
Junhua Yang,
Xiao Wang,
Zhibin Ye
Publication year - 2018
Publication title -
neural regeneration research/neural regeneration research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.93
H-Index - 38
eISSN - 1876-7958
pISSN - 1673-5374
DOI - 10.4103/1673-5374.230299
Subject(s) - lymphangiogenesis , cisterna magna , medicine , genetically modified mouse , lymphatic system , pathology , vascular endothelial growth factor , amyloid beta , in vivo , cerebrospinal fluid , cancer research , transgene , chemistry , biology , disease , cancer , metastasis , biochemistry , vegf receptors , microbiology and biotechnology , gene
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.