Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity.
Endothelial cells of brain capillaries forming the blood-brain barrier play an important role in the pathogenesis and therapy of Alzheimer's disease. Amyloid-β (Aβ) peptides are key pathological elements in the development of the disease. A blood-brain barrier model, based on primary rat brain endothelial cells was used in which the barrier properties were induced by glial cells. The effects of amyloid peptides have been tested on cell viability and barrier functions. Aβ showed toxic effects on primary rat brain endothelial cells measured by MTT dye conversion and the lactate dehydrogenase release. Morphologically cytoplasmic vacuolization, disruption of the structure of cytoplasmic organelles and tight junctions could be observed in brain endothelial cells. Treatment with Aβ1-42 decreased the electrical resistance, and increased the permeability of brain endothelial cell monolayers for both fluorescein and albumin. Serum amyloid P component which stabilizes Aβ fibrils in cortical amyloid plaques and cerebrovascular amyloid deposits significantly potentiated the barrier-weakening effect of Aβ1-42. Sulfated polysaccharide pentosan could decrease the toxic effects of Aβ peptides in brain endothelial cells. It could also significantly protect the barrier integrity of monolayers from damaging actions of peptides. Pentosan modified the size, and significantly decreased the number of amyloid aggregates demonstrated by atomic force microscopy. The present data further support the toxic effects of amyloid peptides on brain endothelial cells, and can contribute to the development of molecules protecting the blood-brain barrier in Alzheimer's disease.
Deli
Mária A
MA
Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary. deli@brc.hu
Veszelka
Szilvia
S
Csiszár
Boglárka
B
Tóth
Andrea
A
Kittel
Agnes
A
Csete
Mária
M
Sipos
Aron
A
Szalai
Anikó
A
Fülöp
Lívia
L
Penke
Botond
B
Abrahám
Csongor S
CS
Niwa
Masami
M
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure*; D002478:Cells, Cultured; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D010426:Pentosan Sulfuric Polyester