School of Medicine, Yunnan University, Kunming, Yunnan, China.
Department of Biomedical Science, AVC, University of Prince Edward Island, Charlottetown, Canada.
Eur J Nutr. 2018 Aug;57(5):1781-1791. doi: 10.1007/s00394-017-1462-7. Epub 2017 May 18.
Interleukin (IL)-1β can activate glial cells to trigger neuroinflammation and neurodegeneration. Lower omega (n)-3 polyunsaturated fatty acids (PUFAs) and lower n-3/n-6 PUFA ratios occur in the brain of patients with Alzheimer's disease (AD). We have previously reported that an n-3 PUFA, eicosapentaenoic acid (EPA), can improve memory and attenuate neurodegeneration-like changes in animal models of AD. However, whether and how EPA modulates glial cell activity and functions remains unclear. The aim of this study was to test the hypothesis that EPA may attenuate neuroinflammation by inhibiting microglial activation and microglia-produced proinflammatory cytokines, and by enhancing the expression of astrocytes-produced neurotrophins and their receptors.
Male Long-Evans rats were fed either palm oil supplemented diet or EPA supplemented diet for 42 days. On day 36 of diet feeding, rats received an intracerebroventricular injection of IL-1β or saline for 7 days. The glial activation, the expression of amyloid precursor protein (APP), calcium-dependent phospholipase (cPL) A2, brain-derived neurotrophic factor (BDNF) and its receptor, and PUFA profile in the hippocampus were analyzed.
IL-1β elevated biomarkers of microglial CD11b and astrocyte GFAP expression, increased the expression of APP, tumor-necrosis factor (TNF)-α, but reduced BDNF and its receptor (TrKB). IL-1β also lowered n-3 EPA and docosapentaenoic acid concentrations but increased n-6 PUFAs and cPLA2 activity in the hippocampus. EPA supplement normalized the n-3 and n-6 PUFA profiles and cPLA2 levels, inhibited glial activation, reduced APP and TNF-α expression, as well as up-regulated BDNF and TrKB.
Supplementation with EPA appear to have potential effects on improving glial over-activation, n3/n6 imbalance and BDNF down-regulation, which contribute to anti-inflammatory and may provide beneficial effects on inflammation-associated disease such as AD.
白细胞介素（IL）-1β可激活神经胶质细胞，引发神经炎症和神经退行性变。阿尔茨海默病（AD）患者的大脑中存在较低水平的ω（n）-3 多不饱和脂肪酸（PUFAs）和较低的 n-3/n-6 PUFA 比值。我们之前的研究表明，n-3 PUFA 二十碳五烯酸（EPA）可改善记忆并减轻 AD 动物模型中的神经退行性变化。但是，EPA 是否以及如何调节神经胶质细胞的活性和功能尚不清楚。本研究旨在验证假设，即 EPA 可能通过抑制小胶质细胞的激活和小胶质细胞产生的促炎细胞因子，以及增强星形胶质细胞产生的神经营养因子及其受体的表达，来减轻神经炎症。
雄性 Long-Evans 大鼠分别用添加棕榈油或 EPA 的饮食喂养 42 天。在饮食喂养的第 36 天，大鼠接受脑室注射 IL-1β或生理盐水 7 天。分析海马中的神经胶质细胞激活、淀粉样前体蛋白（APP）、钙依赖性磷脂酶（cPL）A2、脑源性神经营养因子（BDNF）及其受体和 PUFAs 谱的表达。
IL-1β升高了小胶质细胞 CD11b 和星形胶质细胞 GFAP 的生物标志物表达，增加了 APP、肿瘤坏死因子（TNF）-α的表达，但降低了 BDNF 和其受体（TrKB）的表达。IL-1β还降低了 n-3 EPA 和二十二碳五烯酸的浓度，但增加了 n-6 PUFAs 和 cPLA2 的活性。EPA 补充剂使 n-3 和 n-6 PUFA 谱和 cPLA2 水平正常化，抑制神经胶质细胞激活，减少 APP 和 TNF-α的表达，并上调 BDNF 和 TrKB。
EPA 的补充似乎对改善神经胶质细胞过度激活、n3/n6 失衡和 BDNF 下调具有潜在作用，这有助于抗炎，并可能对 AD 等炎症相关疾病产生有益影响。
