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

查看全文 作　　者：Wenyan [1]Zou;Tinglin [2]Pu;Weixi [2]Feng;Ming [2]Lu;Ying [2]Zheng;Renhong [2]Du;Ming [2]Xiao;Gang [1,2]Hu

机构地区：[1]Department of Pharmacology,School of Medicine and Life Sciences,Nanjing University of Chinese Medicine,138 Xianlin Avenue,Nanjing 210023,Jiangsu,China;[2]Jiangsu Key Laboratory of Neurodegeneratiion,Department of Pharmacology,Nanjing Medical University,101 Longmian Avenue,Nanjing 211166,Jiangsu,China

出　　处：《Translational Neurodegeneration》索引2019年第8卷第1期,共17页

基　　金：This work was supported by grants from the National Natural Science Foundation of China(81671070 and 81473196). 摘　　要：Background:Abnormal aggregation of brainα-synuclein is a central step in the pathogenesis of Parkinson’s disease(PD),thus,it is reliable to promote the clearance ofα-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.Method: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.Results:Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice,accompanied with perivascular aggregation ofα-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra.Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice,causing more severe accumulation ofα-synuclein,glial activation,inflammation,dopaminergic neuronal loss and motor deficits.Conclusion:The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology. 关键词：A53T transgenic mice Α-SYNUCLEIN Glymphatic clearance NEURODEGENERATION Parkinson’s disease

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

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