Changes of blood-brain-barrier function and transfer of amyloid beta in rats with collagen-induced arthritis
Journal
Journal of Neuroinflammation
Journal Volume
18
Journal Issue
1
Date Issued
2021-12-01
Author(s)
Abstract
Background: Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage damage, and systemic inflammation. RA is also associated with the occurrence of neuroinflammation and neurodegenerative diseases. In this study, the impacts of RA on the function of the blood-brain barrier (BBB) and the disposition of amyloid beta (Aβ), including BBB transport and peripheral clearance of Aβ, were investigated in rats with collagen-induced arthritis (CIA), an animal model with similarity to clinical and pathological features of human RA. Methods: CIA was induced in female Lewis rats. In addition to neuroinflammation, the integrity and function of the BBB were examined. The expression of Aβ-transporting proteins at brain blood vessels was measured. Blood-to-brain influx and plasma clearance of Aβ were determined. Results: Both microgliosis and astrogliosis were significantly increased in the brain of CIA rats, compared with controls. In terms of BBB function, the BBB permeability of sodium fluorescein, a marker compound for BBB integrity, was significantly increased in CIA rats. Moreover, increased expression of matrix metalloproteinase-3 (MMP-3) and MMP-9 and decreased expression of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were observed in brain microvessels of CIA rats. In related to BBB transport of Aβ, protein expression of the receptor of advanced glycation end product (RAGE) and P-glycoprotein (P-gp) was significantly increased in brain microvessels of CIA rats. Notably, much higher expression of RAGE was identified at the arterioles of the hippocampus of CIA rats. Following an intravenous injection of human Aβ, significant higher brain influx of Aβ was observed in the hippocampus of CIA rats. Conclusions: Neuroinflammation and the changes of BBB function were observed in CIA rats. The increased RAGE expression at cerebral blood vessels and enhanced blood-to-brain influx of Aβ indicate the imbalanced BBB clearance of Aβ in RA.
Subjects
Amyloid beta | Blood-brain barrier | Collagen-induced arthritis | P-glycoprotein | Receptor of advanced glycation end product
Amyloid beta; Blood-brain barrier; Collagen-induced arthritis; P-glycoprotein; Receptor of advanced glycation end product
SDGs
Other Subjects
ABC transporter subfamily B; advanced glycation end product receptor; amyloid beta protein; gelatinase B; occludin; protein ZO1; stromelysin; advanced glycation end product receptor; Ager protein, rat; amyloid beta protein; amyloid beta-protein (1-42); peptide fragment; animal experiment; animal model; Article; blood brain barrier; collagen-induced arthritis; controlled study; female; hippocampus; nervous system inflammation; nonhuman; protein expression; protein transport; rat; animal; blood brain barrier; brain; complication; experimental arthritis; Lewis rat; metabolic clearance rate; metabolism; microvasculature; pathology; physiology; vascularization; Amyloid beta-Peptides; Animals; Arthritis, Experimental; Blood-Brain Barrier; Brain; Female; Metabolic Clearance Rate; Microvessels; Peptide Fragments; Rats; Rats, Inbred Lew; Receptor for Advanced Glycation End Products
Type
journal article