Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory impairment induced by central administration of interleukin-1beta in rats.
Central or peripheral administration of the proinflammatory cytokine interleukin (IL)-1beta can impair performance on spatial memory tasks and also elevate circulating concentration of corticosterone. The present experiment provides independent confirmation that intracerebroventricular administration of 10 ng IL-1beta in the rat can have a selective effect on the retrieval of trial unique information about the location of food on an eight-arm radial maze. The probable involvement of corticosterone in IL-1beta-induced memory impairment was indicated by elevated corticosterone levels after IL-1beta administration. Further evidence comes from the blockade of the associated impairment in working memory by coadministration of the glucocorticoid receptor antagonist RU486. Ingestion of diet containing omega-3 fatty acid eicosapentaenoic acid (EPA) is known to antagonize the synthesis of prostaglandin (PG) E2 from aracadonic acid, and the present study confirmed that ethyl EPA (1%) reduced IL-1beta-elevated concentrations of PGE2 and corticosterone. Furthermore, rats given the ethyl-EPA diet for 8 weeks were unaffected by the disruptive effects of IL-1beta on working memory. IL-1beta-induced suppression of mitogen-stimulated release of the anti-inflammatory cytokine IL-10 was also blocked by treatment with ethyl-EPA. Collectively, these data demonstrate that IL-1beta can impair memory function by elevating the concentration of corticosterone and that prior consumption of 1% ethyl-EPA can block both the neuroendocrine and cognitive effects of IL-1beta. These findings in turn may indicate beneficial effects of ethyl-EPA in the treatment of cognitive and affective disorders in which inflammation and stress play a critical role.
Song
C
C
Department of Psychiatry, University of British Columbia, Vancouver, Canada. caisong@internchange.ubc.ca
Phillips
A G
AG
Leonard
B E
BE
Horrobin
D F
DF
D000284:Administration, Oral; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000633:toxicity*; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans; D013028:Space Perception / Q000187:drug effects
D007375:Interleukin-1; D016753:Interleukin-10; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; D015232:Dinoprostone; D003345:Corticosterone