Brain Endothelial P-Glycoprotein Level Is Reduced in Parkinson's Disease via a Vitamin D Receptor-Dependent Pathway.

ABSTRACT: The progressive neurodegeneration in Parkinson's disease (PD) is accompanied by neuroinflammation and endothelial vascular impairment. Although the vitamin D receptor (VDR) is expressed in both dopamine neurons and brain endothelial cells, its role in the regulation of endothelial biology has not been explored in the context of PD. In a 6-hydroxydopamine (6-OHDA)-induced PD mouse model, we observed reduced transcription of the VDR and its downstream target genes, CYP24 and MDR1a. The 6-OHDA-induced transcriptional repression of these genes were recovered after the VDR ligand-1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment. Similarly, reduced vascular protein expression of P-glycoprotein (P-gp), encoded by MDR1a, after 6-OHDA administration was reversed by 1,25(OH)2D3. Moreover, marked re

SUBMITTER: Kim H 

PROVIDER: S-EPMC7696047 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature