Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 30, Issue 5, Pages 1109-1119Publisher
KARGER
DOI: 10.1159/000343302
Keywords
CRP; Blood-brain barrier; Permeability; Tight junction; Leptin; Adipokines Inflammation
Categories
Funding
- NIH [DK54880, DK92245, NS62291]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK092245, R56DK054880, P30DK072476, R01DK054880] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS062291] Funding Source: NIH RePORTER
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Background/Aims: Acute phase C-reactive protein (CRP), elevated in obesity and inflammation, is a major binding protein for leptin. It is thought that CRP contributes to leptin resistance by preventing leptin from crossing the blood-brain barrier (BBB). Here we determined how CRP interacts with the BBB and whether it deters leptin from reaching CNS targets. Methods: BBB permeability, compartmental distribution, tracer stability, and expression of tight junction protein and inflammatory marker were determined. Results: CRP was stable in blood, but did not permeate the BBB in trace amounts. However, it increased paracellular permeability at a higher dose. Agouti viable (A(vy)) mice with adult-onset obesity show higher CRP entry into the brain. CRP did not permeate hCMEC/D3 cells nor change zona occludin-1 or cyclooxygenase-2 expression. An intermediate dose of CRP had no effect on leptin transport across the BBB after co-treatment. Thus, acute interactions between CRP and leptin at the BBB level were negligible and did not explain the leptin resistance seen in obesity. Conclusions: The interactions of CRP and the BBB are a two-phase process, with increased paracellular permeability at a high dose that enables its entry into the CNS and serves to induce reactive gliosis and impair CNS function. Copyright (C) 2012 S. Karger AG, Basel
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