Effects of dietary n-3 or n-6 fatty acids on interleukin-1β-induced anxiety, stress, and inflammatory responses in rats

Song, Cai; Li, Xuwen; Leonard, Brian E.; Horrobin, David F.

doi:10.1194/jlr.m300217-jlr200

Cited by 154 publications

(104 citation statements)

References 48 publications

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“…The food was prepared every 3-4 days and stored at 41C (12, 31). Feeding period was 49 days (Song et al, 2003). The rats were about 3.6 months old before experimental testing.…”

Section: Animals and Dietsmentioning

confidence: 99%

“…Previously, we have reported that polyunsaturated omega (n)-3 fatty acid, eicosapentaenoic acid (EPA), attenuated IL-1-induced stress and anxiety-like behavior, and reduced IL-1-induced secretion of prostaglandin (PG) E2 and corticosterone (Song et al, 2003;. EPA has also been shown to reduce PLA2 expression in patients with autistic spectrum disorders .…”

Section: Introductionmentioning

confidence: 99%

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Omega-3 Fatty Acid Ethyl-Eicosapentaenoate Attenuates IL-1β-Induced Changes in Dopamine and Metabolites in the Shell of the Nucleus Accumbens: Involved with PLA2 Activity and Corticosterone Secretion

Song

Kang

et al. 2006

Neuropsychopharmacol

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Previously, we have reported that interleukin-1 b (IL-1) induces changes in dopaminergic (DA) and serotonergic systems in the core of nucleus accumbens (NAc). We have also demonstrated that n-3 fatty acid ethyl-eicosapentaenoate (EPA) can significantly reduce stress and anxiety-like behaviors, corticosterone concentration and peripheral inflammatory response induced by IL-1 administration. Compared to the core, the shell is involved more in emotion, stress and psychiatric diseases. However, the relationship between inflammation and the functions of DA system in the shell has not been studied. Since phospholipase (PL) A2 is a key enzyme in arachidonic acid (AA)-eicosanoids-prostaglandin (PG)E2 pathway, and the change in NAc dopaminergic system has been associated with glucocorticoid stimulation, therefore, the hypotheses of this study are (1) that IL-1 induced changes in DA neurotransmission in the shell may be through PLA2-PGE2-corticosterone pathway; (2) EPA may attenuate IL-1 effects via inhibiting PLA2 activities, which blocks PGE2 stimulation of corticosterone. Using an in vivo microdialysis method, the present study showed that IL-1 administration significantly increased extracellular levels of DA, and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the shell of the NAc. IL-1 also increased blood concentration of corticosterone and PGE2, and increased the activities of cytosolic and sectory of PLA2. IL-1-induced changes were significantly attenuated by EPA treatment. Furthermore, glucorcoticoid receptor antagonist mifepristone (RU486) pretreatment significantly blocked IL-1-induced changes in DA and metabolites. Qquinacrine, a PLA2 antagonist significantly blocked IL-1 induced increase in PGE2 and corticosterone concentrations. These results demonstrated the hypotheses that IL-1 effects may be via PLA2-PGE2-corticosterone pathway and EPA attenuated IL-1 effects may be through the suppression of PLA2 expression, which then reduced PGE2 synthesis and corticosterone secretion. Neuropsychopharmacology (2007) 32, 736-744.

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“…The food was prepared every 3-4 days and stored at 41C (12, 31). Feeding period was 49 days (Song et al, 2003). The rats were about 3.6 months old before experimental testing.…”

Section: Animals and Dietsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Omega-3 Fatty Acid Ethyl-Eicosapentaenoate Attenuates IL-1β-Induced Changes in Dopamine and Metabolites in the Shell of the Nucleus Accumbens: Involved with PLA2 Activity and Corticosterone Secretion

Song

Kang

et al. 2006

Neuropsychopharmacol

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“…However, the time spent on the open arms was almost identical in both groups of mice. There have been reports that IL-1β decreased open arm entries in the EPM suggesting increased anxiety [70,71], but the changes reported were not distinguished from the overall decrease in activity induced by IL-1β. In the present experiments, there were no significant differences between the genotypes in basal locomotion and exploration.…”

Section: Anxiety-related Behaviorsmentioning

confidence: 94%

Feeding, exploratory, anxiety- and depression-related behaviors are not altered in interleukin-6-deficient male mice

Świergiel

Dunn

2006

Behavioural Brain Research

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Interleukin-6 (IL-6) has been implicated in behavioral responses associated with inflammation, sickness behavior and various nervous system disorders. We studied a range of different behaviors in IL-6-knockout (IL-6ko) and wild-type (WT) male mice. No significant differences were observed in ambulatory, exploratory, and stereotypic activities in home or novel cages, in an open field (OF), in the multicompartment chamber (MCC), or in the elevated plus-maze (EPM). IL-6ko mice shed fewer fecal boli than WT mice in the OF, in novel cages and in the MCC although this effect was not statistically significant in the OF. In novel cages, intraperitoneal (i.p.) injection of IL-6 (1 μg) depressed ambulatory activity slightly more in IL-6ko than in WT mice. Restraint and interleukin-1β (IL-1β, 100 ng i.p.) decreased exploration of mice in the MCC and EPM, but there was no indication of altered sensitivity in IL-6ko mice. No significant differences were detected in the tail suspension and the Porsolt forced swim tests. IL-1β and lipopolysaccharide (LPS 1 μg i.p.) injection depressed sweetened milk and solid food intake similarly in IL-6ko and WT mice, but IL-6 had no effect, suggesting that IL-6 is not involved in these effects of IL-1 or LPS. However, IL-1β and LPS depressed body weight more in WT than in IL-6ko mice. Plasma corticosterone and basal concentrations of catecholamines, indoleamines and their metabolites in several brain regions were similar. The responses in these measures to IL-1β and LPS were also similar, except that there were no significant changes in tryptophan and serotonin metabolism in IL-6ko mice. This may reflect a role for IL-6 in the tryptophan and serotonin responses to IL-1 and LPS. It is concluded that the lack of IL-6 is not associated with substantial alterations in several different mouse behaviors, and in the responses to restraint, IL-1β, IL-6 and LPS.

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“…19 A previous study has shown that diet enriched with AA increase GC and PGE2 secretion. 20 Furthermore, EPA can suppress the proinflammatory effects of AA. 19 In a separate experiment, a dietary supplement of ethyl-EPA was employed as a means of attenuating IL-1b-induced activation of PGE2.…”

Section: Introductionmentioning

confidence: 99%

Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory impairment induced by central administration of interleukin-1β in rats

et al. 2003

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Central or peripheral administration of the proinflammatory cytokine interleukin (IL)-1b 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-1b 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-1b-induced memory impairment was indicated by elevated corticosterone levels after IL-1b 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-1b-elevated concentrations of PGE2 and corticosterone. Furthermore, rats given the ethyl-EPA diet for 8 weeks were unaffected by the disruptive effects of IL-1b on working memory. IL-1b-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-1b 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-1b. 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.

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Effects of dietary n-3 or n-6 fatty acids on interleukin-1β-induced anxiety, stress, and inflammatory responses in rats

Cited by 154 publications

References 48 publications

Omega-3 Fatty Acid Ethyl-Eicosapentaenoate Attenuates IL-1β-Induced Changes in Dopamine and Metabolites in the Shell of the Nucleus Accumbens: Involved with PLA2 Activity and Corticosterone Secretion

Omega-3 Fatty Acid Ethyl-Eicosapentaenoate Attenuates IL-1β-Induced Changes in Dopamine and Metabolites in the Shell of the Nucleus Accumbens: Involved with PLA2 Activity and Corticosterone Secretion

Feeding, exploratory, anxiety- and depression-related behaviors are not altered in interleukin-6-deficient male mice

Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory impairment induced by central administration of interleukin-1β in rats

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