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

M. Deli, S. Veszelka, Boglárka Csiszár, Andrea Tóth, A. Kittel, M. Csete, Áron Sipos, Anikó Szalai, L. Fülöp, B. Penke, C. Ábrahám, Masami Niwa

Research output: Contribution to journalArticle

15 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

Fingerprint

Blood-Brain Barrier
Amyloid
Endothelial Cells
Brain
Poisons
Peptides
Amyloid Plaques
Alzheimer Disease
Serum Amyloid P-Component
Cytoplasmic Structures
Tight Junctions
Atomic Force Microscopy
Fluorescein
Electric Impedance
L-Lactate Dehydrogenase
Neuroglia
Organelles
Polysaccharides
Albumins
Permeability

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity. / Deli, M.; Veszelka, S.; Csiszár, Boglárka; Tóth, Andrea; Kittel, A.; Csete, M.; Sipos, Áron; Szalai, Anikó; Fülöp, L.; Penke, B.; Ábrahám, C.; Niwa, Masami.

In: Journal of Alzheimer's Disease, Vol. 22, No. 3, 2010, p. 777-794.

Research output: Contribution to journalArticle

@article{366f186ad1fc44d495bbcda735872f4f,
title = "Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity",
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.",
keywords = "Amyloid-β, blood-brain barrier, brain endothelial cells, glia, pentosan polysulfate, permeability, rat, serum amyloid P component",
author = "M. Deli and S. Veszelka and Bogl{\'a}rka Csisz{\'a}r and Andrea T{\'o}th and A. Kittel and M. Csete and {\'A}ron Sipos and Anik{\'o} Szalai and L. F{\"u}l{\"o}p and B. Penke and C. {\'A}brah{\'a}m and Masami Niwa",
year = "2010",
doi = "10.3233/JAD-2010-100759",
language = "English",
volume = "22",
pages = "777--794",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "3",

}

TY - JOUR

T1 - Protection of the blood-brain barrier by pentosan against amyloid-β-induced toxicity

AU - Deli, M.

AU - Veszelka, S.

AU - Csiszár, Boglárka

AU - Tóth, Andrea

AU - Kittel, A.

AU - Csete, M.

AU - Sipos, Áron

AU - Szalai, Anikó

AU - Fülöp, L.

AU - Penke, B.

AU - Ábrahám, C.

AU - Niwa, Masami

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Amyloid-β

KW - blood-brain barrier

KW - brain endothelial cells

KW - glia

KW - pentosan polysulfate

KW - permeability

KW - rat

KW - serum amyloid P component

UR - http://www.scopus.com/inward/record.url?scp=78650646497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650646497&partnerID=8YFLogxK

U2 - 10.3233/JAD-2010-100759

DO - 10.3233/JAD-2010-100759

M3 - Article

VL - 22

SP - 777

EP - 794

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 3

ER -