Dietary eicosapentaenoic acid normalizes hippocampal omega-3 and 6 polyunsaturated fatty acid profile, attenuates glial activation and regulates BDNF function in a rodent model of neuroinflammation induced by central interleukin-1β administration
Dietary eicosapentaenoic acid normalizes hippocampal omega-3 and 6 polyunsaturated fatty acid profile, attenuates glial activation and regulates BDNF function in a rodent model of neuroinflammation induced by central interleukin-1β administration
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膳食二十碳五烯酸使海马 omega-3 和 6 多不饱和脂肪酸谱正常化，减弱神经胶质活化并调节中枢白细胞介素 1β 给药引起的神经炎症啮齿动物模型中的 BDNF 功能
DOI：
10.1007/s00394-017-1462-7
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发表时间：
2018-08-01
影响因子：
5
通讯作者：
Song, Cai
中科院分区：
文献类型：
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作者：
Dong, Yilong;Xu, Min;Song, Cai
白细胞介素（IL）-1 β可以激活神经胶质细胞，从而引发神经炎症和神经变性。较低的ω（n）-3多不饱和脂肪酸（PUFA）和较低的n-3/n-6 PUFA比率发生在阿尔茨海默病（AD）患者的大脑中。我们以前曾报道，n-3 PUFA，二十碳五烯酸（EPA），可以改善记忆和衰减AD动物模型中的神经退行性变化。然而，EPA是否以及如何调节神经胶质细胞的活性和功能仍不清楚。本研究的目的是测试的假设，EPA可能会减弱神经炎症抑制小胶质细胞活化和小胶质细胞产生的促炎细胞因子，并通过增强星形胶质细胞产生的神经营养因子及其receptors.Male Long-Evans大鼠喂养棕榈油补充饮食或EPA补充饮食42天。在饮食喂养的第36天，大鼠接受脑室内注射IL-1 β或盐水7天。结果表明，IL-1 β可上调小胶质细胞标志物CD 11b和星形胶质细胞GFAP的表达，上调淀粉样前体蛋白（APP）、肿瘤坏死因子（TNF）-α的表达，下调脑源性神经营养因子（BDNF）及其受体（TrKB）的表达。IL-1 β还降低了海马中n-3 EPA和二十二碳五烯酸的浓度，但增加了n-6 PUFA和cPLA 2的活性。EPA补充剂使n-3和n-6 PUFA谱和cPLA 2水平正常化，抑制胶质细胞活化，降低APP和TNF-α表达，以及上调BDNF和TrkB 13 EPA补充剂似乎对改善胶质细胞过度活化、n3/n6失衡和BDNF下调具有潜在作用，这有助于抗炎并且可能对炎症相关疾病如AD提供有益作用。
Interleukin (IL)-1 beta 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-1 beta 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-1 beta elevated biomarkers of microglial CD11b and astrocyte GFAP expression, increased the expression of APP, tumor-necrosis factor (TNF)-alpha, but reduced BDNF and its receptor (TrKB). IL-1 beta 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-alpha 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.