PMID- 33516259
OWN - NLM
STAT- MEDLINE
DCOM- 20210906
LR  - 20210906
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 18
IP  - 1
DP  - 2021 Jan 30
TI  - Changes of blood-brain-barrier function and transfer of amyloid beta in rats with 
      collagen-induced arthritis.
PG  - 35
LID - 10.1186/s12974-021-02086-2 [doi]
LID - 35
AB  - 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 (Abeta), including BBB transport and peripheral 
      clearance of Abeta, 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 Abeta-transporting proteins at brain blood vessels was measured. 
      Blood-to-brain influx and plasma clearance of Abeta 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 Abeta, 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 Abeta, 
      significant higher brain influx of Abeta 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 Abeta indicate the imbalanced BBB clearance of Abeta 
      in RA.
FAU - Lai, Po-Hsuan
AU  - Lai PH
AD  - School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen 
      South Road, Taipei, Taiwan.
FAU - Wang, Ting-Hsuan
AU  - Wang TH
AD  - School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen 
      South Road, Taipei, Taiwan.
FAU - Zhang, Nai-You
AU  - Zhang NY
AD  - School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen 
      South Road, Taipei, Taiwan.
FAU - Wu, Kuo-Chen
AU  - Wu KC
AD  - School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen 
      South Road, Taipei, Taiwan.
FAU - Yao, Chung-Chen Jane
AU  - Yao CJ
AD  - Graduate Institute of Clinical Dentistry, Dental School, College of Medicine, 
      National Taiwan University, Taipei, Taiwan.
FAU - Lin, Chun-Jung
AU  - Lin CJ
AUID- ORCID: 0000-0001-9220-3507
AD  - School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen 
      South Road, Taipei, Taiwan. clementumich@ntu.edu.tw.
LA  - eng
GR  - MOST106-2320-B-002-007-MY3/Ministry of Science and Technology, Taiwan/
PT  - Journal Article
DEP - 20210130
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Ager protein, rat)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (amyloid beta-protein (1-42))
SB  - IM
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Arthritis, Experimental/complications/*metabolism/pathology
MH  - Blood-Brain Barrier/*metabolism/pathology
MH  - Brain/blood supply/*metabolism/pathology
MH  - Female
MH  - Metabolic Clearance Rate/physiology
MH  - Microvessels/metabolism/pathology
MH  - Peptide Fragments/*metabolism
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Receptor for Advanced Glycation End Products/metabolism
PMC - PMC7847579
OTO - NOTNLM
OT  - Amyloid beta
OT  - Blood-brain barrier
OT  - Collagen-induced arthritis
OT  - P-glycoprotein
OT  - Receptor of advanced glycation end product
COIS- The authors declare that they have no competing interests.
EDAT- 2021/02/01 06:00
MHDA- 2021/09/07 06:00
PMCR- 2021/01/30
CRDT- 2021/01/31 20:21
PHST- 2020/08/12 00:00 [received]
PHST- 2021/01/15 00:00 [accepted]
PHST- 2021/01/31 20:21 [entrez]
PHST- 2021/02/01 06:00 [pubmed]
PHST- 2021/09/07 06:00 [medline]
PHST- 2021/01/30 00:00 [pmc-release]
AID - 10.1186/s12974-021-02086-2 [pii]
AID - 2086 [pii]
AID - 10.1186/s12974-021-02086-2 [doi]
PST - epublish
SO  - J Neuroinflammation. 2021 Jan 30;18(1):35. doi: 10.1186/s12974-021-02086-2.