Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity

Mária A. Deli, Szilvia Veszelka, Boglárka Csiszár, Andrea Tóth, Ágnes Kittel, Mária Csete, Áron Sipos, Anikó Szalai, Lívia Fülöp, Botond Penke, Csongor S. Ábrahám, Masami Niwa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)777-794
Number of pages18
JournalJournal of Alzheimer's Disease
Volume22
Issue number3
DOIs
Publication statusPublished - 2010

Keywords

  • Amyloid-β
  • blood-brain barrier
  • brain endothelial cells
  • glia
  • pentosan polysulfate
  • permeability
  • rat
  • serum amyloid P component

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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