Eicosapentaenoic acid confers neuroprotection in the amyloid-beta challenged aged hippocampus.
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.
Lynch
Aileen M
AM
Trinity College Institute of Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.
Loane
David J
DJ
Minogue
Aedín M
AM
Clarke
Rachael M
RM
Kilroy
Dana
D
Nally
Rachel E
RE
Roche
Oran J
OJ
O'Connell
Florence
F
Lynch
Marina A
MA
D000375:Aging; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009457:Neuroglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); D009569:Nitric Oxide; D015118:Eicosapentaenoic Acid