Song Cai, Horrobin David
Neuroscience Division, Department of Psychiatry, University of British Columbia, 2255 Westbrook Mall, Vancouver, BC Canada V6T 2A1.
J Lipid Res. 2004 Jun;45(6):1112-21. doi: 10.1194/jlr.M300526-JLR200. Epub 2004 Apr 1.
Proinflammatory cytokine interleukin (IL)-1beta can cause cognitive impairment, activate the hypothalamic-pituitary-adrenal axis and impair monoaminergic neurotransmission in the rat. IL-1beta 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-1beta. 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-1beta 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-1beta 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.
促炎细胞因子白细胞介素(IL)-1β可导致大鼠认知障碍,激活下丘脑-垂体-肾上腺轴并损害单胺能神经传递。IL-1β还被证明可增加血液中炎症介质前列腺素E2(PGE2)的浓度。ω(n)-3脂肪酸,如二十碳五烯酸(EPA),是鱼油的成分,已被证明可减少促炎细胞因子和PGE2的合成。本研究的目的是确定膳食补充EPA是否会减轻中枢注射IL-1β引起的炎症诱导的空间记忆损害。给大鼠喂食椰子油(含极少量脂肪酸)、大豆油(主要含n-6脂肪酸)或富含乙基-EPA(E-EPA)的椰子油饮食。然后给大鼠脑室内注射IL-1β或生理盐水。本研究结果表明,IL-1诱导的空间记忆缺陷与中枢去甲肾上腺素能和5-羟色胺能(而非多巴胺能)功能损害以及血清皮质酮浓度升高有关。IL-1β还导致海马PGE2浓度升高。长期给予E-EPA可减轻IL-1的这些作用。相比之下,喂食大豆油饮食的大鼠对IL-1给药引起的变化没有影响。