Eicosapentaenoic acid confers neuroprotection in the amyloid-β challenged aged hippocampus
2006; Elsevier BV; Volume: 28; Issue: 6 Linguagem: Inglês
10.1016/j.neurobiolaging.2006.04.006
ISSN1558-1497
AutoresAileen Lynch, David J. Loane, Aedín M. Minogue, Rachael M. Clarke, Dana Kilroy, Rachel E. Nally, Óran J. Roche, F O'Connell, Marina A. Lynch,
Tópico(s)Immune Response and Inflammation
ResumoAmong 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.
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