How does serum amyloid P component get into the brain?
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1
HAS, Institute of Biophysics, Biological Research Center, Hungary
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2
Gedeon Richter Ltd., Hungary
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3
HAS, Laboratory of Molecular Biology and Genetics, Institute of Experimental Medicine, Hungary
Serum amyloid P component (SAP), a circulating pentraxin produced by the liver, does not penetrate the brain in physiological conditions. In Alzheimer’s disease SAP is one of the components of the amyloid plaques and stabilizes the protein deposits. The goal of this study was to investigate the transport of SAP in animal experiments and in a rat in vitro model of the blood-brain barrier using primary cell cultures. No human SAP (hSAP) could be detected in rat brain sections by immunohistochemistry or by ELISA in healthy animals after intravenous injection of the pentraxin. Furthermore, when hSAP was injected to the left hippocampus of rats it was rapidly effluxed. Rat brain endothelial cells took up FITC-labelled hSAP from both luminal and abluminal direction with a higher luminal release indicating active efflux mechanism. We demonstrated that the blood-brain barrier permeability is increased to hSAP in Salmonella typhimurium lipopolysaccharide-injected mice. Lipopolysaccharide induced hSAP extravasation to brain parenchyma and also increased the number of cerebral vessels labelled with FITC-hSAP, while no hSAP leakage to brain was seen in vehicle-treated mice. Our data indicate, that active efflux mechanisms at the level of the blood-brain barrier protect the brain from SAP penetration in physiological conditions. Damage to the protective mechanisms of the blood-brain barrier due to pathological insults, like inflammation may result in a higher SAP concentration in brain and can contribute to the pathomechanism of neurodegenerative diseases, like Alzheimer’s disease.
Conference:
IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010.
Presentation Type:
Poster Presentation
Topic:
Homeostatic and neuroendocrine systems
Citation:
Veszelka
S,
Deli
M,
Laszy
J,
Németh
L,
Obál
I,
Fábián
L,
Thi Khue
DN,
Ábrahám
C,
Pázmány
T,
Szabó
G and
Urbányi
Z
(2010). How does serum amyloid P component get into the brain?.
Front. Neurosci.
Conference Abstract:
IBRO International Workshop 2010.
doi: 10.3389/conf.fnins.2010.10.00082
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Received:
22 Apr 2010;
Published Online:
22 Apr 2010.
*
Correspondence:
Mária Deli, HAS, Institute of Biophysics, Biological Research Center, Szeged, Hungary, deli.maria@brc.hu