Fatty acid and lipid profiles in models of neuroinflammation and mood disorders. Application of high field NMR, gas chromotography and liquid chromotography-tandem mass spectrometry to investigate the effects of atorvaststin in brain and liver lipids and explore brain lipid changes in the FSL model of depression.

Abstract

Lipids are important for the structural and physiological functions of neuronal cell membranes. Alterations in their lipid composition may result in membrane dysfunction and subsequent neuronal deficits that characterise various disorders. This study focused on profiling lipids of aged and LPS-treated rat brain and liver tissue with a view to explore the effect of atorvastatin in neuroinflammation, and examining lipid changes in different areas of rat brain of the Flinders Sensitive Line (FSL) rats, a genetic model of depression. Lipids and other analytes extracted from tissue samples were analysed with proton nuclear magnetic resonance spectroscopy (1H-NMR), gas chromatography (GC) and liquid chromatography-tandem mass spectroscopy (LC/ESI-MS/MS). Changes in the lipid profiles suggested that brain and liver responded differently to ageing and LPS-induced neuroinflammation. In the aged animals, n-3 PUFA were reduced in the brain but were increased in the liver. However, following treatment with LPS, these effects were not observed. Nevertheless, in both models, brain concentration of monounsaturated fatty acids was increased while the liver was able to maintain its monounsaturated fatty acid concentration. Atorvastatin reversed the reduction in n-3 PUFA in the aged brain without reducing brain and liver concentration of cholesterol. These findings further highlight alterations in lipid metabolism in agerelated neuroinflammation and show that the anti-inflammatory actions of atorvastatin may include a modulation of fatty acid metabolism. When studying the FSL model, there were differences in the lipid profile of different brain areas of FSL rats compared to Sprague-Dawley controls. In all brain areas, arachidonic acid was increased in the FSL rats. Docosahexaenoic acid and ether lipids were reduced, while cholesterol and sphingolipids were increased in the hypothalamus of the FSL rats. Furthermore, total diacylglycerophospholipids were reduced in the prefrontal cortex and hypothalamus of the FSL rats. These results show differences in the lipid metabolism of the FSL rat brain and may be suggestive of changes occurring in the brain tissue in depression.