Rat brain docosahexaenoic acid metabolism is not altered by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide

Abstract

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.

Figure 1

Concentration of esterified DHA in the stable brain phospholipid pools from control and LPS-treated rats following an intravenous infusion of [1-¹⁴C]DHA. Values are the means ± SD (n=7). Abbreviations are: DHA, docosahexaenoic acid; PtdEtn, phosphatidylethanolamine; PlsEtn, plasmenylethanolamine; PtdIns, phosphatidylinositol; PtdSer, phosphatidylserine; PtdCho, phosphatidylcholine; PlsCho, plasmenylcholine.

Figure 2

Plasma radioactivity in control and LPS-treated rats during the intravenous infusion of [1-¹⁴C]DHA. Values represent the means ± SD (n=7).

Figure 3

Brain microsomal long-chain acyl-CoA synthetase activity using [¹⁴C]AA or [¹⁴C]DHA as substrate from control or LPS-treated rats. Values are the means ± SD (n=5). Abbreviations are; AA-CoA, arachidonoyl-CoA and DHA-CoA, docosahexaenoyl-CoA.