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Increased brain docosahexaenoic acid has no effect on the resolution of neuroinflammation following intracerebroventricular lipopolysaccharide injection
Neurochemistry international ( IF 4.4 ) Pub Date : 2018-05-22 , DOI: 10.1016/j.neuint.2018.05.010
Marc-Olivier Trépanier , Kathryn E. Hopperton , Vanessa Giuliano , Mojgan Masoodi , Richard P. Bazinet

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.



中文翻译:

脑二十二碳六烯酸增加对脑室内脂多糖注射后神经炎症的缓解没有影响

外周炎症的消退曾经被认为是被动过程,但现在的新研究表明,它是由衍生自omega-3多不饱和脂肪酸(n-3 PUFA)的专门亲分解脂质介体(SPM)介导的主动过程。 。但是,这尚未在神经炎症中得到说明。这项研究的目的是测量神经炎症的分辨率,并测试增加的大脑二十二碳六烯酸(DHA)是否会影响神经炎症的分辨率。

用鱼油或红花油喂养的C57Bl / 6小鼠,fat-1小鼠及其野生型同窝仔在左心室接受脂多糖(LPS)。然后在各个时间点对动物实施安乐死以进行免疫组织化学,基因表达和脂质组分析。

术后5天观察到小胶质细胞活化高峰,分辨指数为10天。在LPS注射后28天内,约有350个基因发生了显着变化,其中130个基因在注射后3天内发生了独特的变化。在生物活性介质池中未观察到变化。但是,一些溶血磷脂种类在术后24小时减少。当大脑DHA增加时,小胶质细胞密度不能更快地分解,也不会改变基因表达。

总之,神经炎症的缓解似乎与SPM无关。大脑DHA的增加对该模型没有影响。

更新日期:2018-05-22
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