Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA.
Neurochem Int. 2010 Feb;56(3):501-7. doi: 10.1016/j.neuint.2009.12.010. Epub 2009 Dec 22.
In a rat model of neuroinflammation, produced by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide (LPS), we reported that the brain concentrations of non-esterified brain arachidonic acid (AA, 20:4 n-6) and its eicosanoid products PGE(2) and PGD(2) were increased, as were AA turnover rates in certain brain phospholipids and the activity of AA-selective cytosolic phospholipase A(2) (cPLA(2)). The activity of Ca(2+)-independent iPLA(2), which is thought to be selective for the release of docosahexaenoic acid (DHA, 22:6 n-3) from membrane phospholipid, was unchanged. In the present study, we measured parameters of brain DHA metabolism in comparable artificial cerebrospinal fluid (control) and LPS-infused rats. In contrast to the reported changes in markers of AA metabolism, the brain non-esterified DHA concentration and DHA turnover rates in individual phospholipids were not significantly altered by LPS infusion. The formation rates of AA-CoA and DHA-CoA in a microsomal brain fraction were also unaltered by the LPS infusion. These observations indicate that LPS-treatment upregulates markers of brain AA but not DHA metabolism. All of which are consistent with other evidence that suggest different sets of enzymes regulate AA and DHA recycling within brain phospholipids and that only selective increases in brain AA metabolism occur following a 6-day LPS infusion.
在神经炎症的大鼠模型中,通过对大脑室 6 天的细菌脂多糖(LPS)输注,我们报告说大脑中非酯化脑花生四烯酸(AA,20:4n-6)及其二十碳烯酸产物 PGE(2)和 PGD(2)的浓度增加,某些脑磷脂中的 AA 周转率和 AA 选择性胞质型 PLA(2)(cPLA(2))的活性增加。钙非依赖性 iPLA(2)的活性不变,人们认为 iPLA(2)选择性地从膜磷脂释放二十二碳六烯酸(DHA,22:6n-3)。在本研究中,我们在可比的人工脑脊液(对照)和 LPS 输注大鼠中测量了脑 DHA 代谢的参数。与 AA 代谢标志物的报道变化相反,LPS 输注并未显著改变大脑中非酯化 DHA 浓度和各磷脂中的 DHA 周转率。脑微粒体部分中 AA-CoA 和 DHA-CoA 的形成率也不受 LPS 输注的影响。这些观察结果表明,LPS 处理上调了大脑 AA 的标志物,但未上调 DHA 代谢标志物。所有这些都与其他证据一致,即不同的酶组调节大脑磷脂中 AA 和 DHA 的再循环,并且只有在 LPS 输注 6 天后才会选择性地增加大脑 AA 代谢。