Eicosapentaenoic acid confers neuroprotection in the amyloid-beta challenged aged hippocampus

Neurobiol Aging. 2007 Jun;28(6):845-55. doi: 10.1016/j.neurobiolaging.2006.04.006. Epub 2006 May 22.


Among the changes that occur in the hippocampus with age, is a deficit in long-term potentiation (LTP). This impairment is associated with inflammatory changes, which are typified by increased concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). Activated microglia are the most likely cell source of IL-1beta, but data demonstrating an age-related increase in microglial activation is equivocal. Here we demonstrate that the age-related deficit in LTP is accompanied by increased expression of cell surface markers of activated microglia (major histocompatibility complex II and CD40) and increased IL-1beta production, and that these changes may be stimulated by interferon-gamma. Treatment of aged rats with eicosapentaenoic acid (EPA) attenuates these changes and we suggest that IL-4 mediates the action of EPA. We demonstrate that aged rats exhibit an exaggerated response to intracerebroventricular injection of beta-amyloid peptide 1-40 (Abeta). Thus Abeta inhibited LTP in aged, but not young, rats and induced a further increase in hippocampal IL-1beta concentration. Of particular significance is the demonstration that EPA protects the aged brain so that the increased vulnerability to Abeta is ameliorated in EPA-treated rats.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Amyloid beta-Peptides / administration & dosage*
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • CD40 Antigens / metabolism
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Eicosapentaenoic Acid / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / physiology*
  • Histocompatibility Antigens Class II / metabolism
  • Injections, Intraventricular
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Male
  • Neuroglia / drug effects
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Peptide Fragments / administration & dosage*
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar


  • Amyloid beta-Peptides
  • CD40 Antigens
  • Cytokines
  • Histocompatibility Antigens Class II
  • Neuroprotective Agents
  • Peptide Fragments
  • RNA, Messenger
  • amyloid beta-protein (1-40)
  • Nitric Oxide
  • Eicosapentaenoic Acid