Quantitative analysis of phospholipids containing arachidonate and docosahexaenoate chains in microdissected regions of mouse brain

Axelsen, Paul H.; Murphy, Robert C.

doi:10.1194/jlr.d001750

Cited by 48 publications

(51 citation statements)

References 62 publications

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“…Thick (0.5 mm) tissue slices were manually cut from the sectioning block with a razor blade, placed onto a glass slide, flash frozen and stored at −70 C° until needed. Microdissection was carried out using previously described methods13. Briefly, the tissue on the glass slide was placed onto a styrofoam tray with a frozen ‘cold pack’ on the bottom and pieces of dry ice around the periphery.…”

Section: Methodsmentioning

confidence: 99%

Relationship between MALDI IMS Intensity and Measured Quantity of Selected Phospholipids in Rat Brain Sections

Hankin

Murphy

2010

Anal. Chem.

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MALDI IMS positive ion images of rat brain show a regional distribution of phosphocholine species that is striking in the apparent distinctiveness, and reproducibility of such depictions. The interpretation of these images, specifically the relationship between MALDI IMS ion intensity and the amount of the phosphocholine (PC) species in the tissue is complicated by numerous factors such as ion suppression, ion molecule chemistry, and effects of tissue structure. This study was designed to test the hypothesis that the intensity of PC molecular species does relate to the quantity of molecules in a tissue sample. A set of comparison studies for a limited but representative selection of cell-derived PC molecular species, was carried out using LC/MS/MS to measure the amounts of these species in brain tissue extracts. There was good correlation between the MALDI IMS ion abundance of PC molecular species and the relative abundance of corresponding PC molecular species in microdissected regions analyzed by LC/MS/MS.

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Section: Methodsmentioning

confidence: 99%

Relationship between MALDI IMS Intensity and Measured Quantity of Selected Phospholipids in Rat Brain Sections

Hankin

Murphy

2010

Anal. Chem.

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“…Moreover, the increase of stearoyl-arachidonoyl-phospholipids (PC, PE, PI) denotes a profound membrane remodeling in the APP/PS1 mice as it is one of the most abundant species on the brain [42], being cortex the most affected region. Therefore, alterations in phospholipids metabolism appears to have a multifactorial origin involving over-activation of phospholipases, peroxisomal dysfunction and abnormal fatty acid composition of phospholipids.…”

Section: Metabolitementioning

confidence: 99%

Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer's disease by direct infusion mass spectrometry

González‐Domínguez

García-Barrera

Vitórica

et al. 2015

Journal of Pharmaceutical and Biomedical Analysis

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The identification of pathological mechanisms underlying to Alzheimer's disease is of great importance for the discovery of potential markers for diagnosis and disease monitoring. In this study, we investigated regional metabolic alterations in brain from the APP/PS1 mice, a transgenic model that reproduces well some of the neuropathological and cognitive deficits observed in human Alzheimer's disease. For this purpose, hippocampus, cortex, cerebellum and olfactory bulbs were analyzed using a high-throughput metabolomic approach based on direct infusion mass spectrometry. Metabolic fingerprints showed significant differences between transgenic and wild-type mice in all brain tissues, being hippocampus and cortex the most affected regions. Alterations in numerous metabolites were detected including phospholipids, fatty acids, purine and pyrimidine metabolites, acylcarnitines, sterols and amino acids, among others. Furthermore, metabolic pathway analysis revealed important alterations in homeostasis of lipids, energy management, and metabolism of amino acids and nucleotides. Therefore, these findings demonstrate the potential of metabolomic screening and the use of transgenic models for understanding pathogenesis of Alzheimer's disease.

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“…LC/MS techniques can identify and quantify large numbers of individual PL species, which is not possible with GC/MS [18]. In this study, we employed LC/MS to examine the effect of dietary ω3-PUFA deprivation on the concentration of PUFA-containing PL species and some of their oxidation products in rat brain.…”

Section: Introductionmentioning

confidence: 99%

Increased ω6-Containing Phospholipids and Primary ω6 Oxidation Products in the Brain Tissue of Rats on an ω3-Deficient Diet

et al. 2016

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Polyunsaturated fatty acyl (PUFA) chains in both the ω3 and ω6 series are essential for normal animal brain development, and cannot be interconverted to compensate for a dietary deficiency of one or the other. Paradoxically, a dietary ω3-PUFA deficiency leads to the accumulation of docosapentaenoate (DPA, 22:5ω6), an ω6-PUFA chain that is normally scarce in the brain. We applied a high-precision LC/MS method to characterize the distribution of DPA chains across phospholipid headgroup classes, the fatty acyl chains with which they were paired, and the extent to which they were oxidatively damaged in the cortical brain of rats on an ω3-deficient diet. Results indicate that dietary ω3-PUFA deficiency markedly increased the concentrations of phospholipids with DPA chains across all headgroup subclasses, including plasmalogen species. The concentrations of phospholipids containing docosahexaenoate chains (22:6ω3) decreased 20–25%, while the concentrations of phospholipids containing arachidonate chains (20:4ω6) did not change significantly. Although DPA chains are more saturated than DHA chains, a larger fraction of DPA chains were monohydroxylated, particularly among diacyl-phosphatidylethanolamines and plasmalogen phosphatidylethanolamines, suggesting that they were disproportionately subjected to oxidative stress. Differences in the pathological significance of ω3 and ω6 oxidation products suggest that greater oxidative damage among the ω6 PUFAs that increase in response to dietary ω3 deficiency may have pathological significance in Alzheimer’s disease.

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Quantitative analysis of phospholipids containing arachidonate and docosahexaenoate chains in microdissected regions of mouse brain

Cited by 48 publications

References 62 publications

Relationship between MALDI IMS Intensity and Measured Quantity of Selected Phospholipids in Rat Brain Sections

Relationship between MALDI IMS Intensity and Measured Quantity of Selected Phospholipids in Rat Brain Sections

Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer's disease by direct infusion mass spectrometry

Increased ω6-Containing Phospholipids and Primary ω6 Oxidation Products in the Brain Tissue of Rats on an ω3-Deficient Diet

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