Lipid profilling of polyunsaturated fatty acid - treated mouse brain and plasma. Investigation into polyunsaturated fatty acid (PUFA)-induced neuroprotection

Abstract

Pre-treatment with polyunsaturated fatty acids or bioactive lipid mediators has been shown to reduce neuronal injury in rodent models of focal ischaemia, but the molecular mechanisms underlying this neuroprotection are unclear. In this study, we aimed to investigate whether systemic administration of alpha linolenic acid (ALA) leads to changes in the profile of mouse brain phospholipid and bioactive lipid mediators in both mouse brain and plasma within the previously determined neuroprotection time window. Mass spectrometry (MS) and tandem mass spectrometry (MS/MS) allowed us to detect and identify 47 phospholipids in mouse cerebral cortex, including several phospholipid species not previously reported in brain lipidomic studies. These included a phosphatidylethanolamine species with m/z 720 that has been associated with retinal stem cells. No widespread changes in cerebral cortex phospholipid composition were observed following intravenous ALA. Several significant changes in lipid mediators (P<0.05 with two-way ANOVA and post hoc Dunnett¿s t test) were detected in ALA-treated animals compared to untreated and vehicle-injected animals. Many of the affected lipid mediators are ligands for prostanoid receptors which have been demonstrated to play a role in the development of brain injury following cerebral ischaemia, implying that changes in bioactive lipid mediators or modulation of prostanoid receptors may occur following ALA pre-treatment in mice. This study illustrates the potential of advanced lipidomic analysis as a novel tool for neurochemists.