Understanding the role of perivascular macrophages in Parkinson's disease pathophysiology (original) (raw)

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) associated to the aggregation of α-synuclein (α-Syn) that forms intraneuronal inclusions. In addition, mounting evidence suggest that neuro-immune interactions, favoured by cerebrovascular alterations, are involved in the pathomechanisms of PD. In this work, we focus on a myeloid population that surrounds blood vessels: perivascular macrophages (PVMs). We show that both in PD patients and in a mouse model of degenerative synucleinopathy, there is an increased proliferative recruitment of PVMs within the SN. We also found that specific ablation of PVMs aggravates the degenerative phenotype in synucleinopathic mice. PVMs-mediated neuroprotection is not likely linked to regulatory mechanisms of microglial cell response. Interestingly, the absence of PVMs is associated with higher vascular expression of VCAM-1 and enhanced infiltration of CD4+ and CD8+ T-cells, whose pa...