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.

中文翻译：

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阻断脑膜淋巴引流会加重过度表达突变 α-突触核蛋白的小鼠的帕金森病样病理

脑α-突触核蛋白的异常聚集是帕金森病（PD）发病机制的核心步骤，因此促进α-突触核蛋白的清除以预防和治疗PD是可靠的。最近的研究揭示了淋巴系统和脑膜淋巴管在清除脑大分子中的重要作用，然而，它们的病理生理方面仍然难以捉摸。通过结扎颈深淋巴结来阻断 18 周龄 A53T 小鼠的脑膜淋巴引流。六周后，系统分析了 glymphatic 功能和 PD 样表型。A53T 小鼠脑脊液示踪剂的 Glymphatic 流入减少，伴随着 α-突触核蛋白的血管周围聚集和黑质中水通道蛋白 4 表达的极化受损。颈部淋巴结扎加重了 A53T 小鼠的淋巴功能障碍，导致更严重的 α-突触核蛋白积累、神经胶质激活、炎症、多巴胺能神经元丢失和运动障碍。结果表明，脑淋巴清除功能障碍可能是 PD 病理的加重因素。