Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 3E2, Canada; Lipid Biology, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.
Neurochem Int. 2018 Sep;118:115-126. doi: 10.1016/j.neuint.2018.05.010. Epub 2018 May 22.
Resolution of inflammation in the periphery was once thought to be a passive process, but new research now suggests it is an active process mediated by specialized pro-resolving lipid mediators (SPM) derived from omega-3 polyunsaturated fatty acids (n-3 PUFA). However, this has yet to be illustrated in neuroinflammation. The purpose of this study was to measure resolution of neuroinflammation and to test whether increasing brain docosahexaenoic acid (DHA) affects the resolution of neuroinflammation. C57Bl/6 mice, fat-1 mice and their wildtype littermates, fed either fish oil or safflower oil, received lipopolysaccharide (LPS) in the left lateral ventricle. Animals were then euthanized at various time points for immunohistochemistry, gene expression, and lipidomic analyses. Peak microglial activation was observed at 5 days post-surgery and the resolution index was 10 days. Of the approximately 350 genes significantly changed over the 28 days post LPS injection, 130 were uniquely changed at 3 days post injection. No changes were observed in the bioactive mediator pools. However, a few lysophospholipid species were decreased at 24hr post surgery. When brain DHA is increased, microglial cell density did not resolve faster and did not alter gene expression. In conclusion, resolution of neuroinflammation appears to be independent of SPM. Increasing brain DHA had no effect in this model.
炎症反应在周围组织的消退曾被认为是一个被动的过程，但新的研究表明，它是由源自 ω-3 多不饱和脂肪酸（n-3 PUFA）的专门的促解决脂质介质（SPM）介导的主动过程。然而，这尚未在神经炎症中得到证实。本研究旨在测量神经炎症的消退情况，并检验增加大脑二十二碳六烯酸（DHA）是否会影响神经炎症的消退。C57Bl/6 小鼠、fat-1 小鼠及其野生型同窝仔鼠分别用鱼油或红花油喂养，在左侧侧脑室给予脂多糖（LPS）。然后，在不同时间点处死动物进行免疫组织化学、基因表达和脂质组学分析。在手术后第 5 天观察到小胶质细胞激活的峰值，消退指数为第 10 天。在 LPS 注射后 28 天内显著变化的大约 350 个基因中，有 130 个在注射后 3 天发生了独特变化。生物活性介质池未发生变化。然而，一些溶血磷脂在手术后 24 小时减少。当大脑 DHA 增加时，小胶质细胞密度并没有更快地消退，也没有改变基因表达。总之，神经炎症的消退似乎与 SPM 无关。在该模型中，增加大脑 DHA 没有效果。
