Structural mass spectrometry analysis of lipid changes in a Drosophila epilepsy model brain

Kliman, Michal; Vijayakrishnan, Niranjana; Wang, Lily; Tapp, John T.; Broadie, Kendal; McLean, John A.

doi:10.1039/b927494d

Cited by 22 publications

(18 citation statements)

References 40 publications

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“…The specific conditions used for lipid fragmentation are described elsewhere. 34 Spectra of standard reference compounds were obtained under identical conditions to those that were used from on tissue. MassLynx was also used for instrument control and data analysis.…”

Section: Methodsmentioning

confidence: 99%

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Matusch¹,

Fenn

Depboylu³

et al. 2012

Anal. Chem.

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Several complementary mass spectrometric imaging techniques allow mapping of various analytes within biological tissue sections. Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) quantitatively detects elements and isotopes with very high sensitivity and a particularly high dynamical range. Matrix-assisted laser desorption/ionization ion mobility mass spectrometry (MALDI-IM-MS) allows a pixel-by-pixel classification and identification of biomolecules.In order to dispose of the healthy hemisphere as an internal calibrant in addition to routinely used external standards, adjacent brain sections of mice with a unilateral 6-OHDA lesion of the medial forebrain bundle were chosen as exemplary samples. We demonstrate a comprehensive way of data acquisition and analysis by coregistering mass spectrometric data on photomicrographs as common reference space and thus providing trimodal spatial information. Registering subsequent planar element maps yielded continuous 3-dimensional data sets. Furthermore, we introduce a correction of MSI data for variable slice thickness applicable to all MSI techniques. In the present case, we observed increased concentrations of iron, manganese, and copper in the lesioned substantia nigra while monounsaturated lipid levels were decreased in the identical region of interest. Our techniques provide new insights into the intricate spatial relationship of morphology and chemistry within tissue.

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Section: Methodsmentioning

confidence: 99%

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Matusch¹,

Fenn

Depboylu³

et al. 2012

Anal. Chem.

Self Cite

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“…Recently IM-MS measurement strategies have demonstrated great utility in the analysis of highly complex biological samples ranging from serum [51] to intact tissue [24; 75; 76]. The advantages of IM-MS for complex sample analysis are several fold, including (i) simultaneous characterization of all biomolecular species in a sample, (ii) minimizing sample losses and sample preparation artifacts arising from extensive purification procedures, (iii) preserving the biomolecular context, such as that encountered with conjugate species ( e.g.…”

Section: Section 4 – the Future Outlook Of Im-ms Research For Lipidomicsmentioning

confidence: 99%

“…Recently, IM-MS was utilized by Kliman et al to separate lipid signals from matrix cluster signals in a relative quantitation study of lipids from a Drosophila eas 2 epilepsy model mutant. By removing the extraneous contribution of matrix cluster signals from the lipid analysis, statistically significant changes in the abundance of several lipid species were observed between mutant and wildtype brain tissue samples [76]. …”

Section: Section 4 – the Future Outlook Of Im-ms Research For Lipidomicsmentioning

confidence: 99%

Lipid analysis and lipidomics by structurally selective ion mobility-mass spectrometry

Kliman

May

McLean

2011

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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199

156

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Recent advances in mass spectrometry approaches to the analysis of lipids include the ability to incorporate both lipid class identification with lipid structural information for increased characterization capabilities. The detailed examination of lipids and their biosynthetic and biochemical pathways made possible by novel instrumental and bioinformatics approaches is advancing research in fundamental cellular and medical studies. Recently, high-throughput structural analysis has been demonstrated through the use of rapid gas-phase separation on the basis of the ion mobility (IM) analytical technique combined with mass spectrometry (IM-MS). While IM-MS has been extensively utilized in biochemical research for peptide, protein and small molecule analysis, the role of IM-MS in lipid research is still an active area of development. In this review of lipid-based IM-MS research, we begin with an overview of three contemporary IM techniques which show great promise in being applied towards the analysis of lipids. Fundamental concepts regarding the integration of IM-MS are reviewed with emphasis on the applications of IM-MS towards simplifying and enhancing complex biological sample analysis. Finally, several recent IM-MS lipid studies are highlighted and the future prospects of IM-MS for integrated omics studies and enhanced spatial profiling through imaging IM-MS are briefly described.

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“…CDP-ethanolamine donates phosphoethanolamine to diacylglycerol to generate PE, which is mediated by CDP-ethanolamine phosphotransferase (encoded by bbc ) (Dobrosotskaya et al, 2002). In addition, the level of PE is reduced in eas whole flies and heads (Kliman et al, 2010; Nyako et al, 2001; Pavlidis et al, 1994). Therefore, we asked whether the dendrite morphogenesis defects were due to insufficient PE synthesis through the CDP–ethanolamine pathway.…”

Section: Resultsmentioning

confidence: 99%

Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

et al. 2017

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Summary Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas), which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE) synthesis, and two other enzymes in this synthesis pathway are required cell-autonomously in sensory neurons for dendrite growth and stability. Further, we show that the level of Sterol Regulatory Element Binding Protein (SREBP) activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

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Structural mass spectrometry analysis of lipid changes in a Drosophila epilepsy model brain

Cited by 22 publications

References 40 publications

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale

Lipid analysis and lipidomics by structurally selective ion mobility-mass spectrometry

Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

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