Premium
Modulation of amyloid‐β‐induced and age‐associated changes in rat hippocampus by eicosapentaenoic acid
Author(s) -
Minogue Aedín M.,
Lynch Aileen M.,
Loane David J.,
Herron Caroline E.,
Lynch Marina A.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04848.x
Subject(s) - long term potentiation , endocrinology , medicine , hippocampal formation , dentate gyrus , hippocampus , chemistry , eicosapentaenoic acid , neuroinflammation , receptor , biology , fatty acid , inflammation , biochemistry , polyunsaturated fatty acid
The age‐related deficit in long‐term potentiation (LTP) in the dentate gyrus is positively correlated with hippocampal concentration of the pro‐inflammatory cytokine, interleukin‐1β (IL‐1β). Previous evidence also indicates that the inhibition of LTP induced by intracerebroventricular injection of amyloid‐β 1–40 (Aβ) is accompanied by increased hippocampal IL‐1β concentration and IL‐1β‐stimulated signalling, specifically activation of the stress‐activated protein kinase, c‐jun N‐terminal kinase (JNK). We considered that the underlying age‐related neuroinflammation may render older rats more susceptible to Aβ administration and, to investigate this, young, middle‐aged and aged rats were injected intracerebroventricularly with Aβ or vehicle. Hippocampal IL‐1β concentration, JNK phosphorylation, expression of the putative Aβ receptor, Receptor for advanced glycation end products (RAGE) and the microglial cell surface marker, CD40 were assessed. We report that Aβ inhibited LTP in a concentration‐dependent manner in young rats and that this was accompanied by concentration‐dependent increases in hippocampal IL‐1β and expression of phosphorylated JNK, RAGE and CD40. While 20 μmol/L Aβ exerted no significant effect on LTP in young rats, it inhibited LTP in middle‐aged and aged rats and the increased vulnerability of aged rats was associated with increased IL‐1β concentration. Treatment of rats with eicosapentaenoic acid attenuated the inhibitory effect of 60 μmol/L Aβ on LTP in young rats and the effect of 20 μmol/L Aβ in middle‐aged and aged rats. We present evidence which indicates that the effect of eicosapentaenoic acid may be linked with its ability to stimulate activation of peroxisome proliferator‐activated receptor gamma.