Blocking meningeal lymphatic drainage aggravates Parkinson's disease-like pathology in mice overexpressing mutated α-synuclein

Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis of Parkinson's disease (PD), thus, it is reliable to promote the clearance of α-synuclein to prevent and treat PD. Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels...

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Published in:Translational neurodegeneration 2019-03, Vol.8 (1), p.7-7, Article 7
Main Authors: Zou, Wenyan, Pu, Tinglin, Feng, Weixi, Lu, Ming, Zheng, Ying, Du, Renhong, Xiao, Ming, Hu, Gang
Format: Article
Language:English
Subjects:
A53T transgenic mice
Alzheimer's disease
Animal cognition
Aquaporins
Brain
Glymphatic clearance
Lymphatic system
Neurodegeneration
Parkinson's disease
Pathogenesis
Pathology
Transgenic animals
α-Synuclein
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container_title Translational neurodegeneration
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creator Zou, Wenyan
Pu, Tinglin
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Xiao, Ming
Hu, Gang
description Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis of Parkinson's disease (PD), thus, it is reliable to promote the clearance of α-synuclein to prevent and treat PD. Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules, however, their pathophysiological aspects remain elusive. Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes. Six weeks later, glymphatic functions and PD-like phenotypes were systemically analyzed. Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice, accompanied with perivascular aggregation of α-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra. Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice, causing more severe accumulation of α-synuclein, glial activation, inflammation, dopaminergic neuronal loss and motor deficits. The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology.
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subjects A53T transgenic mice
Alzheimer's disease
Animal cognition
Aquaporins
Brain
Glymphatic clearance
Lymphatic system
Neurodegeneration
Parkinson's disease
Pathogenesis
Pathology
Transgenic animals
α-Synuclein
title Blocking meningeal lymphatic drainage aggravates Parkinson's disease-like pathology in mice overexpressing mutated α-synuclein
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