Docosahexaenoic and eicosapentaenoic acids increase neuronal death in response to HuPrP82-146 and Aβ1-42

Clive Bate, Victoria Marshall, Laura Colombo, Luisa Diomede, Mario Salmona, Alun Williams

Research output: Contribution to journalArticle

Abstract

Dietary supplements containing polyunsaturated fatty acids (PUFA) are frequently taken for their perceived health benefits including a possible reduction in cognitive decline in the elderly. Here we report that pre-treatment with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) significantly reduced the survival of cortical or cerebellar neurons incubated with HuPrP82-146, a peptide derived from the prion protein, or with Aβ1-42, a peptide found in Alzheimer's disease. Treatment with DHA or EPA reduced the free cholesterol content of neuronal membranes. This did not affect the amount of FITC-HuPrP82-146 ingested by neurons, but increased the kinetics of incorporation. In untreated neurons, FITC-HuPrP82-146 migrated to caveolin-1 containing lipid rafts. The addition of HuPrP82-146 also triggered the migration of cytoplasmic phospholipase A2 (cPLA2) into caveolin-1 containing rafts, and increased prostaglandin E2 production. Activation of cPLA2 and prostaglandin E2 production were both increased in neurons pre-treated with DHA. These results are consistent with DHA or EPA altering cell membranes resulting in increased amounts of HuPrP82-146 localising to caveolin-1 containing rafts, increased activation of cPLA2, prostaglandin E2 production, caspase-3 activity and reduced neuronal survival. Such observations raise the possibility that some PUFA supplements may accelerate neuronal loss in the terminal stages of prion or Alzheimer's diseases.

Original languageEnglish
Pages (from-to)934-943
Number of pages10
JournalNeuropharmacology
Volume54
Issue number6
DOIs
Publication statusPublished - May 2008

Fingerprint

Eicosapentaenoic Acid
Docosahexaenoic Acids
Caveolin 1
Phospholipases A2
Dinoprostone
Neurons
Fluorescein-5-isothiocyanate
Unsaturated Fatty Acids
Alzheimer Disease
Peptides
Prion Diseases
Insurance Benefits
Dietary Supplements
Caspase 3
Cholesterol
Cell Membrane
Lipids
Membranes
Therapeutics

Keywords

  • Cytoplasmic phospholipase A
  • Lipid rafts
  • Neurotoxicity
  • Polyunsaturated fatty acids
  • Prion
  • Prostaglandins

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Docosahexaenoic and eicosapentaenoic acids increase neuronal death in response to HuPrP82-146 and Aβ1-42 . / Bate, Clive; Marshall, Victoria; Colombo, Laura; Diomede, Luisa; Salmona, Mario; Williams, Alun.

In: Neuropharmacology, Vol. 54, No. 6, 05.2008, p. 934-943.

Research output: Contribution to journalArticle

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