Eicosapentaenoic acid and gamma-linolenic acid increase hippocampal concentrations of IL-4 and IL-10 and abrogate lipopolysaccharide-induced inhibition of long-term potentiation.
Inflammatory changes in brain exert a negative impact on cognitive function and in animal studies, these changes are associated with impairment in hippocampal-dependent learning paradigms and in long-term potentiation (LTP), which is a putative biological substrate for learning and/or memory. Lipopolysaccharide (LPS), a component of the cell wall of gram negative bacteria, induces inflammatory changes in the brain and leads to impairment of LTP. Since eicosapentaenoic acid (EPA) inhibits LPS-induced changes in vitro, we assessed the possibility that treatment of rats with EPA, alone or in combination with gamma-linolenic acid (GLA) might inhibit LPS-induced changes in vivo. The data presented indicate that the LPS-induced inhibition of LTP and decrease in hippocampal concentration of anti-inflammatory cytokines IL-10 and IL-4 are blocked in rats treated with EPA, GLA or both. The evidence suggests that these effects may be coupled with fatty acid-induced up-regulation of peroxisome proliferator-activated receptor-gamma which possesses known anti-inflammatory effects.
Kavanagh
Thady
T
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
Lonergan
P E
PE
Lynch
Marina A
MA
D000818:Animals; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D008070:Lipopolysaccharides; D047495:PPAR gamma; D016753:Interleukin-10; D015847:Interleukin-4; D017965:gamma-Linolenic Acid; D015118:Eicosapentaenoic Acid