Brain Lipidome Research Articles

Organization and Evolution of Brain Lipidome Revealed by Large-Scale Analysis of Human, Chimpanzee, Macaque, and Mouse Tissues

Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution.

Quantitative spatial analysis of the mouse brain lipidome by pressurized liquid extraction surface analysis.

Here we describe a novel surface sampling technique termed pressurized liquid extraction surface analysis (PLESA), which in combination with a dedicated high-resolution shotgun lipidomics routine enables both quantification and in-depth structural characterization of molecular lipid species extracted directly from tissue sections. PLESA uses a sealed and pressurized sampling probe that enables the use of chloroform-containing extraction solvents for efficient in situ lipid microextraction with a spatial resolution of 400 μm. Quantification of lipid species is achieved by the inclusion of internal lipid standards in the extraction solvent. The analysis of lipid microextracts by nanoelectrospray ionization provides long-lasting ion spray which in conjunction with a hybrid ion trap-orbitrap mass spectrometer enables identification and quantification of molecular lipid species using a method with successive polarity shifting, high-resolution Fourier transform mass spectrometry (FTMS), and fragmentation analysis. We benchmarked the performance of the PLESA approach for in-depth lipidome analysis by comparing it to conventional lipid extraction of excised tissue homogenates and by mapping the spatial distribution and molar abundance of 170 molecular lipid species across different anatomical mouse brain regions.

Ultra performance liquid chromatography - mass spectrometry studies of formalin-induced alterations of human brain lipidome.

The development of 'omics' sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin-fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin-induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N-methylation and N-formylation of amine-containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin-fixed samples.

Alterations in phospholipidomic profile in the brain of mouse model of depression induced by chronic unpredictable stress

Depression is a worldwide disability disease associated with high morbidity and has increased dramatically in the last few years. The differential diagnosis and the definition of an individualized therapy for depression are hampered by the absence of specific biomarkers. The aim of this study was to evaluate the phospholipidomic profile of the brain and myocardium in a mouse model of depression induced by chronic unpredictable stress (CUS). The lipidomic profile was evaluated by thin layer and liquid chromatography and mass spectrometry and lipid oxidation was estimated by FOX II assay. Antioxidant enzyme activity and the oxidized/reduced glutathione (GSH/GSSG) ratio were also evaluated. Results showed that chronic stress affects primarily the lipid profile of the brain, inducing an increase in lipid hydroperoxides, which was not detected in the myocardium. A significant decrease in phosphatidylinositol (PI) and in cardiolipin (CL) relative contents and also oxidation of CL and a significant increase of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were observed in the brain of mice after unpredictable chronic stress conditions. In the myocardium only an increase in PC content was observed. Nevertheless, both organs present a decreased GSH/GSSG ratio when compared to control groups, corroborating the occurrence of oxidative stress. The enzyme activities of catalase (CAT) and superoxide dismutase (SOD) were found to be decreased in the myocardium and increased in the brain, while glutathione reductase (GR) was decreased in the brain. Our results indicate that in a mouse model for studying depression induced by CUS, the modification of the expression of oxidative stress-related enzymes did not prevent lipid oxidation in organs, particularly in the brain. These observations suggest that depression has an impact on the brain lipidome and that further studies are needed to better understand lipids role in depression and to evaluate their potential as future biomarkers.

Alterations in Mouse Brain Lipidome after Disruption of CST Gene: A Lipidomics Study

To investigate the effects of a critical enzyme, cerebroside sulfotransferase (CST), involving sulfatide biosynthesis on lipid (particularly sphingolipid) homeostasis, herein, we determined the lipidomes of brain cortex and spinal cord from CST null and heterozygous (CST(-/-) and CST(+/-), respectively) mice in comparison to their wild-type littermates by multi-dimensional mass spectrometry-based shotgun lipidomics. As anticipated, we demonstrated the absence of sulfatide in the tissues from CST(-/-) mice and found that significant reduction of sulfatide mass levels was also present, but in an age-dependent manner, in CST(+/-) mice. Unexpectedly, we revealed that the profiles of sulfatide species in CST(+/-) mice were significantly different from that of littermate controls with an increase in the composition of species containing saturated and hydroxylated fatty acyl chains. Contrary to the changes of sulfatide levels, shotgun lipidomics analysis did not detect significant changes of the mass levels of other lipid classes examined. Taken together, shotgun lipidomics analysis demonstrated anticipated sulfatide mass deficiency in CST defect mouse brain and revealed novel brain lipidome homeostasis in these mice. These results might provide new insights into the role of CST in myelin function.

Effects of a high-fat, high-cholesterol diet on brain lipid profiles in apolipoprotein E ɛ3 and ɛ4 knock-in mice

Apolipoprotein E (ApoE) is important in facilitating the transport of lipids (cholesterol, phospholipids, and sulfatides) and plays a fundamental role in normal lipid metabolism. High cholesterol levels increases the risk of developing Alzheimer's disease. In this study, we investigated the effects of a high-fat high cholesterol (HFHC) diet on brain lipid profiles in 95 young and aged APOE ɛ3 and ɛ4 knock-in mice to determine whether diet leads to altered brain levels of a number of glycerophospholipids, sphingolipids, cholesterol precursors, cholesterol, cholesterol oxidation products, and cholesterol esters. The results in this study revealed significant changes in lipid levels. The HFHC-enriched diet influenced the levels of cholesterol esters. A sharp increase in cholesterol ester levels, particularly in the aged APOE ɛ4 diet-enriched group, might be suggestive of abnormal acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT) activity and/or levels. Age exerts appreciable effects on the brain lipidome, especially with regard to polar lipid species.

Seasonal acclimatization of brain lipidome in a eurythermal fish (Carassius carassius) is mainly determined by temperature

Crucian carp (Carassius carassius) is an excellent vertebrate model for studies on temperature adaptation in biological excitable membranes, since the species can tolerate temperatures from 0 to +36 degrees C. To determine how temperature affects the lipid composition of brain, the fish were acclimated for 4 wk at +30, +16, or +4 degrees C in the laboratory, or seasonally acclimatized individuals were captured from the wild throughout the year (temperature = +1 to +23 degrees C), and the brain glycerophospholipid and sphingolipid compositions were analyzed in detail by electrospray-ionization mass spectrometry. Numerous significant temperature-related changes were found in the molecular species composition of the membrane lipids. The most notable and novel finding was a large (approximately 3-fold) increase of the di-22:6n-3 phosphatidylserine and phosphatidylethanolamine species in the cold. Since the increase of 22:6n-3 in the total fatty acyl pool of the brain was small, the formation of di-22:6n-3 aminophospholipid species appears to be a specific adaptation to low temperature. Such highly unsaturated species could be needed to maintain adequate membrane fluidity in the vicinity of transporters and other integral membrane proteins. Plasmalogens increased somewhat at higher temperatures, possibly to protect membranes against oxidation. The modifications of brain lipidome during the 4-wk laboratory acclimation were, in many respects, similar to those found in the wild, which indicates that the seasonal changes observed in the wild are temperature dependent rather than induced by other environmental factors.