Glymphatic system

Psychiatry

Internal medicine

Dopaminergic

Pathology

Neurology

Neuroscience

Lymphatic system

Immunology

Inflammation

Disease

Cerebrospinal fluid

Lymph

Parkinson's disease

Interstitial fluid

Substantia nigra

Dopamine

Medicine

Biology

Translational Neurodegeneration

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.

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