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

Autor: Tinglin Pu, Ying Zheng, Wenyan Zou, Ming Xiao, Weixi Feng, Ming Lu, Ren-Hong Du, Gang Hu
Rok vydání: 2019
Předmět:
Zdroj: Translational Neurodegeneration, Vol 8, Iss 1, Pp 1-17 (2019)
Translational Neurodegeneration
ISSN: 2047-9158
Popis: Background 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. 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 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. Conclusion The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology. Electronic supplementary material The online version of this article (10.1186/s40035-019-0147-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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