Docosahexaenoic acid reduces amyloid-β induced toxicity in cells of the neurovascular unit

Szilvia Veszelka, Andrea E. Tóth, Fruzsina R. Walter, Zsolt Datki, Emese Mózes, Lívia Fülöp, Zsolt Bozsó, Éva Hellinger, Monika Vastag, Barbara Orsolits, Zsuzsanna Környei, Botond Penke, Mária A. Deli

Research output: Article

34 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β peptides (Aβ) as perivascular deposits and senile plaques in the brain. The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) has been associated with decreased amyloid deposition and reduced risk in AD in several epidemiological trials; however the exact underlying molecular mechanism remains to be elucidated. The aim of the study was to test whether DHA can exert a direct protective effect on the elements of the neurovascular unit, such as neurons, glial cells, brain endothelial cells, and pericytes, treated with Aβ42 (15 μM). A dose-dependent high cellular toxicity was found in viability assays in all cell types and on acute hippocampal slices after treatment with Aβ42 small oligomers prepared in situ from an isopeptide precursor. The cell morphology also changed dramatically in all cell types. In brain endothelial cells, damaged barrier function and increased para- and transcellular permeability were observed after peptide treatment. The production of reactive oxygen species was elevated in pericytes and endothelial and glial cells. DHA (30 μM) significantly decreased the Aβ 42-induced toxic effects in all cell types measured by viability assays, and protected the barrier integrity and functions of brain endothelial cells. DHA also decreased the elevated rhodamine 123 accumulation in brain endothelial cells pre-treated with Aβ42 indicating an effect on efflux pump activity. These results indicate for the first time that DHA can protect not only neurons but also the other elements of the neurovascular unit from the toxic effects of Aβ42 and this effect may be beneficial in AD.

Original languageEnglish
Pages (from-to)487-501
Number of pages15
JournalJournal of Alzheimer's Disease
Volume36
Issue number3
DOIs
Publication statusPublished - 2013

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ASJC Scopus subject areas

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

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