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

Abstract

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.

Damaging effects of a high-fat diet to the brain and cognition: A review of proposed mechanisms

“…For instance, a systemic or intraventricular IL-1β injection gives rise to spatial memory impairments in rats, 59,60 and significant effects of injected IL-1β on the win-shift paradigm of the radial arm maze have been reported. 61 Bickford et al have previously shown that an indirect IL-1 blockade, using a caspase ***-1 inhibitor, has significant improvement effects on memory in aged rats, suggesting that IL-1 is involved in impaired performance on memory tasks with aging. 62 IL-1 has also been shown to be an important player in inflammation-induced memory impairments in rodents, following a chronic inflammation paradigm.…”

Biological Mechanism of Antidepressant Effect of Omega–3 Fatty Acids: How Does Fish Oil Act as a ‘Mind-Body Interface’?

“…Chronic low-grade systemic inflammation plays a significant role in several chronic medical diseases as well as depression [78] . Interestingly, animals fed high AA diet or treated with PGE2 produced sickness behaviours of anorexia, low activity, change in sleep pattern and attention [56,57] . n-3 PUFAs have an anti-inflammatory effect by antagonizing membrane AA and reducing PGE2 synthesis [79] .…”

“…An AA-enriched diet can increase glucocorticoid and PGE2 secretion as well as anxiety behaviour [54] . In contrast, EPA can suppress proinflammatory effects of AA [55] , thereby reducing PGE2 synthesis [55] and attenuating interleukin (IL)-1 ␤ -induced activation of PGE2 [56] . Foods enriched with ethyl-EPA, but not soybean oil, significantly attenuated most of the IL-1 ␤ -induced sickness, stress and anxiety-like behaviours [57] .…”

n-3 Fatty Acid-Derived Lipid Mediators against Neurological Oxidative Stress and Neuroinflammation

“…Furthermore, expression of IL-10 is also blocked by ethyl-EPA treatment. Based on these results, it is proposed that ethyl-EPA treatment produces beneficial effects in those neuropsychiatric disorders in which inflammation and oxidative stress play a critical role (Song et al, 2004;Song et al, 2009;Farooqui, 2009).…”

“…Thus, inadequacy of EPA and DHA in neural membranes may contribute to cholinergic, dopaminergic, and glutamatergic receptor dysfunction in synapses associated with the hippocampal neurons, and growing evidence suggests that low levels of DHA in the brain are associated not only with neurotraumatic, neurodegenerative, and neuropsychiatric diseases, but also with peroxisomal disorders (Farooqui, 2009). Dietary intake of EPA antagonizes the synthesis of PGE 2 from ARA and reduces the IL-1β-mediated increase in levels of PGE 2 (Song et al, 2004;Song et al, 2009). Furthermore, expression of IL-10 is also blocked by ethyl-EPA treatment.…”