Imaging MALDI Mass Spectrometry Using an Oscillating Capillary Nebulizer Matrix Coating System and Its Application to Analysis of Lipids in Brain from a Mouse Model of Tay-Sachs/Sandhoff Disease

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• 作者：Yanfeng Chen ; Jeremy Allegood ; Ying Liu ; Elaine Wang ; Begoñ ; a Cachó ; n-Gonz&aacute ; lez ; Timothy M. Cox ; Alfred H. Merrill ; Jr. ; M. Cameron Sullards
• 刊名：Analytical Chemistry
• 出版年：2008
• 出版时间：April 15, 2008
• 年：2008
• 卷：80
• 期：8
• 页码：2780 - 2788
• 全文大小：880K
• 年卷期：v.80,no.8(April 15, 2008)
• ISSN：1520-6882

文摘

The quality of tissue imaging by matrix-assisted laserdesorption/ionization mass spectrometry (MALDI-MS)depends on the effectiveness of the matrix deposition,especially for lipids that may dissolve in the solvent usedfor the matrix application. This article describes the useof an oscillating capillary nebulizer (OCN) to spray smalldroplets of matrix aerosol onto the sample surface forimproved matrix homogeneity, reduced crystal size, andcontrolled solvent effects. This system was then appliedto the analysis of histological slices of brains from micewith homozygous disruption of the hexb gene (hexb^-/-),a model of Tay-Sachs and Sandhoff disease, versus thefunctionally normal heterozygote (hexb^+/-) by imagingMALDI-MS. This allowed profiling and localization ofmany different lipid species, and of particular interest,ganglioside GM2, asialo-GM2 (GA2), and sulfatides (ST).The presence of these compounds was confirmed byanalysis of brain extracts using electrospray ionization inconjunction with tandem mass spectrometry (MS/MS).The major fatty acid of the ceramide backbone of bothGM2 and GA2 was identified as stearic acid (18:0) versusnervonic acid (24:1) for ST by both tissue-imaging MS andESI-MS/MS. GM2 and GA2 were highly elevated inhexb^-/- and were both localized in the granular cell regionof the cerebellum. ST, however, was localized mainly inmyelinated fiber (white matter) region of the cerebellumas well as in the brain stem with a relatively uniformdistribution and had similar relative signal intensity forboth hexb^+/- and hexb^-/- brain. It was also observed thatthere were distinct localizations for numerous other lipidsubclasses; hence, imaging MALDI-MS could be used for"lipidomic" studies. These results illustrate the usefulnessof tissue-imaging MALDI-MS with matrix deposition byOCN for histologic comparison of lipids in tissues suchas brains from this mouse model of Tay-Sachs andSandhoff disease.