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Journal of Lipid Research, Vol. 45, 1112-1121, June 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Omega-3 fatty acid ethyl-eicosapentaenoate, but not soybean oil, attenuates memory impairment induced by central IL-1ß administration

Cai Song^1,* and David Horrobin^2,

^* Neuroscience Division, Department of Psychiatry, University of British Columbia, 2255 Westbrook Mall, Vancouver, BC Canada, V6T 2A1
Laxdale Ltd., Scotland, UK

¹ To whom correspondence should be addressed. e-mail: caisong{at}interchange.ubc.ca

Proinflammatory cytokine interleukin (IL)-1ß can cause cognitive impairment, activate the hypothalamic-pituitary-adrenal axis and impair monoaminergic neurotransmission in the rat. IL-1ß has also been shown to increase the concentration of the inflammatory mediator prostaglandin E2 (PGE2) in the blood. Omega (n)-3 fatty acids, such as eicosapentaenoic acid (EPA), which are components of fish oil, have been shown to reduce both the proinflammatory cytokines and the synthesis of PGE2. The purpose of this study was to determine whether dietary supplements of EPA would attenuate the inflammation-induced impairment of spatial memory by centrally administered IL-1ß. Rats were fed with a diet of coconut oil (contained a negligible quantity of fatty acids), soybean oil (contained mainly n-6 fatty acids), or a diet of coconut oil enriched with ethyl-EPA (E-EPA). The rats were then injected intracerebroventricularly with IL-1ß or saline.

The results of this study demonstrated that the IL-1-induced deficit in spatial memory was correlated with an impairment of central noradrenergic and serotonergic (but not dopaminergic) function and an increase in the serum corticosterone concentration. IL-1ß also caused an increase in the hippocampal PGE2 concentration. These effects of IL-1 were attenuated by the chronic administration of E-EPA. By contrast, rats fed with the soybean oil diet showed no effect on the changes induced by the IL-1 administration.

Abbreviations: 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, serotonin; AA, arachidonic acid; AD, Alzheimer's disease; COX, cyclooxygenase; CRF, corticotrophin release factor; DA, dopamine; DHA, docosahexaenoic acid; DOPAC, 3,4-dihydroxyphenylacetic acid; E-EPA, ethyl-eicosapentaenoic acid; GC, glucocortidoids; HPA, hypothalamus pituitary adrenal; HVA, homovanillic acid; icv, intracerebroventricular; IL, interleukin; LTP, long-term potentiation; MHPG, 3-methoxy-4-hydroxyphenethyleneglycol; NA, noradrenaline; PGE2, prostaglandin E2; TRP, tryptophan

Supplementary key words eicosapentaenoic acid • interleukinß • interleukin-1ß-administration • spatial memory • hippocampus • monoamine neurotransmitters • prostaglandin E2 • corticosterone

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